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Biomedical subjects

J H Cho

Publications and source records attributed to J H Cho.

At least 109 records · Page 6Linked to original sources
PubMed1998

Hepatitis C virus envelope DNA-based immunization elicits humoral and cellular immune responses.

The vaccine development for hepatitis C virus (HCV) is highly urgent to prevent non A and non B hepatitis. It was recently shown that the HCV envelope proteins appeared to the key viral antigens to induce protective immunity. To generate immune responses to the HCV envelope proteins on the DNA-based immunization, various envelope gene-containing plasmids were constructed. For efficient expression and secretion of envelope proteins, the signal sequence of each envelope protein was replaced with either herpes simplex virus type-1 (HSV-1) gD or signal sequence of gD and truncated C-terminal hydrophobic regions of envelope proteins. The intramuscular injection of these plasmids generated a significant level of antibody titers to the E1 and E2 proteins, which maximally reached 850 and 25,000 respectively. The secreted form of each envelope protein and the fusion of the highly immunogenic gD proteins were shown to have no significant effect on generating immune responses to the envelope proteins. In addition, immunized rats appeared to generate antibodies directed to the homologous HVR-1 peptide. Splenic lymphocytes from immunized rats were shown to induce significant T-cell proliferative responses with the stimulation of recombinant E1 and E2 proteins. Our results demonstrated that the HCV envelope-DNA based immunization could elicit both humoral and cellular immune responses.

Amino Acid Sequence↗
PubMed1998

Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: evidence for epistasis between 1p and IBD1.

The idiopathic inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, non-Mendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) = 2.29, P = 5.7 x 10(-4)), with greatest significance for non-Ashkenazim Caucasians (MLod = 3.39, P = 3.92 x 10(-5)), and at chromosome 1p (MLod = 2.65, P = 2.4 x 10(-4)) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 x 10(-4)), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1, in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 x 10(-3)), particularly among Ashkenazim (MLod = 1.51, P = 7.8 x 10(-3)); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC.

Chromosome Mapping↗
PubMed1998

A dynamin-like protein in Arabidopsis thaliana is involved in biogenesis of thylakoid membranes.

Dynamin, a GTP-binding protein found in rat brain, plays a role in endocytosis. Suborganellar fractionation studies of Arabidopsis leaf tissue revealed that a dynamin-like protein, ADL1, is localized in the thylakoid membranes of chloroplasts. This notion was supported further by in vivo targeting experiments using an ADL1-green fluorescent fusion protein and immunogold labeling with the anti-ADL1 antibody. Transgenic plants harboring various deletion mutant genes of ADL1 had a yellow leaf phenotype where the cells had very few chloroplasts. In addition, the remaining chloroplasts appeared morphologically not fully developed. The detailed structure of the chloroplasts revealed by electron microscopy showed a greatly reduced amount of thylakoid membranes. Also, the level of thylakoid membrane proteins such as the light-harvesting complex II and CP29 was greatly reduced in these transgenic plants. When we examined the expression of the ADL1 deletion mutant genes, these genes were highly expressed at the transcriptional level. However, the mutant ADL1s were not detectable at the protein level by Western blot analysis. Moreover, the endogenous ADL1 protein level was greatly reduced in these transgenic plants, probably due to a post-transcriptional silencing effect of the transgenes. We propose, therefore, that ADLl is involved in the biogenesis of thylakoid membranes.

Arabidopsis↗
PubMed1998

American families with Crohn's disease have strong evidence for linkage to chromosome 16 but not chromosome 12.

BACKGROUND & AIMS: Two European genome-wide screens for inflammatory bowel disease have identified two significant regions of linkage on chromosomes 16 (IBD1) and 12 (IBD2) and two regions with suggestive levels of significance (chromosomes 3p and 7q). The aim of this study was to determine if there was evidence for linkage to these regions in non-Jewish and Ashkenazi Jewish families multiplex for Crohn's disease from the United States. METHODS: One hundred forty-eight affected relative pairs, 34% Ashkenazim, were genotyped with 10-14 highly polymorphic markers overlying each candidate region. Nonparametric multipoint and two-point linkage analyses were performed. RESULTS: Significant evidence for replication of linkage was found only for the chromosome 16 locus, IBD1, maximal at D16S769 (nonparametric linkage score [NPL], 2.49; P = 0.007). Analysis by ethnicity showed stronger evidence for Ashkenazim (D16S769; NPL = 2. 52; P = 0.007) than for non-Jewish white populations (D16S401; NPL = 1.40; P = 0.082). There was no significant evidence for replication on chromosome 12 (IBD2). Minimal evidence for extension of linkage evidence was observed for the chromosomes 3p and 7q regions. CONCLUSIONS: American families, particularly Ashkenazim, have significant evidence for the Crohn's disease susceptibility locus, IBD1, on chromosome 16, but not for IBD2 on chromosome 12.

Chromosome Mapping↗
PubMed1998

Altered topographic expression of p21WAF1/CIP1/SDI1, bcl2 and p53 during gastric carcinogenesis.

The accumulation of wild-type p53 protein results in two pathways, cell cycle G1 arrest by p21WAF1/CIP1/SDI1 and apoptosis inhibited by bcl2, which together carry out the tumor suppressor function. Since genetic alterations of p53 are frequently observed in gastric cancers, the expression of p21 and bcl2 may be altered in gastric carcinogenesis. We therefore analyzed normal mucosa, nondysplastic lesions, hyperplastic polyps, adenomas and carcinomas of the human stomach using immuno-histochemistry, polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing. In normal gastric mucosa, the expression of p21, bcl2 and p53 was topographically restricted: a) p21 expression was limited to foveolar epithelial cells; b) bcl2 and p53 expression was confined to only a few regenerative epithelial cells of the mucous neck region. In chronic gastritis or intestinal metaplasia, topographic expression became more obvious. This topographic expression was altered in hyperplastic polyps and adenomas. Hyper-plastic polyp showed an increased p21 and p53 expression with no bcl2 expression. Where as bcl2 expression increased and extended up parabasal and superficial dysplastic epithelium, p21 expression increased and was limited to surface dysplastic epithelium. Weak p53 expression was in full thickness of dysplastic epithelium. p21 and bcl2 expression in adenoma was higher than in intestinal type of carcinoma. In carcinomas, this topography was abrogated, but p53 mutation (36%) was present. There was no relationship between p53, p21 and bcl2 expression. As a result, in normal gastric epithelial cells, there was a precisely ordered topographic pattern of p21, bcl2 and wild-type p53 expression that becomes disordered during neoplasia. These results suggest that altered cell cycle and apoptosis control by wild-type p53 and its mediators appears to be an early event in gastric carcinogenesis that may facilitate tumor progression.

Adenocarcinoma↗
PubMed1998

Cre/loxP-mediated excision and amplification of large segments of the Escherichia coli genome.

The isolation and amplification of large, predetermined segments of a genome from its host have been explored. The prototype of our approach was the excisional replication of some viruses such as the lambda-lysogen. Similar machinery was used to excise and amplify large genomic segments of Escherichia coli in its host. Two loxP sequences for a site-specific recombinase Cre, together with a conditional replication origin (pi-dependent gamma-ori), were inserted into the genome by homologous recombination at predetermined sites, 50-100 kb apart. Cre and pir200 which encodes the site-specific recombinase Cre and an ori-specific replication protein pi, respectively, were also introduced into the genome. The predetermined genomic segments flanked by the loxP sequences were excised and amplified upon induction of the cre and pir200 genes which were under the control of the tet promoter. This excised and amplified DNA could be easily purified as a large plasmid. This procedure can provide an alternative to conventional cloning methods by obtaining predetermined large genomic segments directly from the original organisms. In this study, using the Cre/loxP site-specific recombination and pi/gamma-ori replication system of plasmid R6K, a procedure was devised that could isolate a large segment of the E. coli genome and demonstrated the feasibility of the procedure by excising and amplifying the 50-kb trg-narZ and 100-kb trg-hipA regions of the E. coli W3110 genome.

Bacterial Proteins↗
PubMed1998

Infection with Helicobacter pylori expressing the cagA gene is not associated with an increased risk of developing peptic ulcer diseases in Korean patients.

BACKGROUND: Helicobacter pylori strains possessing the cagA gene have been postulated to have a disease-specific relationship to peptic ulcer. The purpose of this study was to investigate the relationship between the infection with Helicobacter pylori expressing the cagA gene and the development of peptic ulcer diseases in Korean patients. METHODS: Genomic DNA and bacterial mRNA in the gastric mucosa were amplified by polymerase chain reaction (PCR) and reverse transcription PCR, using synthetic oligonucleotide primers to cagA genes to compare the prevalence of cagA genes in 35 patients with non-ulcer gastritis and 99 patients with gastric or duodenal ulcer disease (53 and 46, respectively). Two different primer sets for the cagA gene were used. The first primer set amplified a 298-bp region (nucleotides 1751-2048), and the second set amplified a 349-bp region (nucleotides 1228-1249). RESULTS: The expected 298 and 349-bp PCR amplicons were identified as follows: 1) 32 (91.4%) and 30 (85.7%) of 35 non-ulcer gastritis patients; 2) 5 1 (96.2%) and 50 (94.3%) of 53 benign gastric ulcer patients; and 3) 46 (100.0%) and 40 (87.0%) of 46 duodenal ulcer patients, respectively. CONCLUSION: These results strongly suggest that the cagA gene will not prove to be a useful marker to distinguish disease-specific H. pylori strains in the development of peptic ulcer diseases in Korean patients.

Antigens, Bacterial↗
PubMed1998

The role of Müller's muscle reconsidered.

It is a traditional teaching that the levator aponeurosis is the main transmitter of the levator palpebrae muscle. However, there are several points that raise doubts in this fundamental concept of the levator aponeurosis as being the primary interconnecting mechanism in upper lid elevation. Despite the structural integrity of the levator complex, drooping of the upper eyelids is seen to develop in situations such as Horner's syndrome and in times of excessive fatigue and sleepiness. Amid the controversy in the literature regarding the specific role of the levator aponeurosis in the lid-elevating mechanism, we have observed that the levator aponeurosis fails to make constant attachment to the tarsal plate. This has led us to speculate on the possible role of the posterior lamella - Müller's muscle - as the primary transmitter of the levator muscle action to the tarsal plate.

Blepharoptosis↗
PubMed1998

Optimal induction of hepatitis C virus envelope-specific immunity by bicistronic plasmid DNA inoculation with the granulocyte-macrophage colony-stimulating factor gene.

In this study, we have constructed various DNA vaccine vectors that carried hepatitis C virus (HCV) envelope genes without and with the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in several different ways. In Buffalo rats that received plasmids carrying the HCV envelope genes, which encode envelope proteins E1 and E2, both antibody and lymphoproliferative responses against these proteins were induced. These responses were greatly enhanced by the codelivery of the GM-CSF gene. In particular, inoculation with a bicistronic plasmid that independently expressed the GM-CSF gene and the envelope genes in the same construct generated the highest antibody titers and significantly increased lymphoproliferative responses against these proteins. Moreover, strong antibody responses to homologous and heterologous hypervariable region 1 peptides were elicited in the immunized rats.

Amino Acid Sequence↗
PubMed1998

A novel DNA-binding protein bound to the mitochondrial inner membrane restores the null mutation of mitochondrial histone Abf2p in Saccharomyces cerevisiae.

The yeast mitochondrial HMG-box protein, Abf2p, is essential for maintenance of the mitochondrial genome. To better understand the role of Abf2p in the maintenance of the mitochondrial chromosome, we have isolated a multicopy suppressor (YHM2) of the temperature-sensitive defect associated with an abf2 null mutation. The function of Yhm2p was characterized at the molecular level. Yhm2p has 314 amino acid residues, and the deduced amino acid sequence is similar to that of a family of mitochondrial carrier proteins. Yhm2p is localized in the mitochondrial inner membrane and is also associated with mitochondrial DNA in vivo. Yhm2p exhibits general DNA-binding activity in vitro. Thus, Yhm2p appears to be novel in that it is a membrane-bound DNA-binding protein. A sequence that is similar to the HMG DNA-binding domain is important for the DNA-binding activity of Yhm2p, and a mutation in this region abolishes the ability of YHM2 to suppress the temperature-sensitive defect of respiration of the abf2 null mutant. Disruption of YHM2 causes a significant growth defect in the presence of nonfermentable carbon sources such as glycerol and ethanol, and the cells have defects in respiration as determined by 2,3,5,-triphenyltetrazolium chloride staining. Yhm2p may function as a member of the protein machinery for the mitochondrial inner membrane attachment site of mitochondrial DNA during replication and segregation of mitochondrial genomes.

Amino Acid Sequence↗
PubMed1998

Aldosterone stimulates intestinal Na+ absorption in rats by increasing NHE3 expression of the proximal colon.

Na+ retention by the colon in response to salt deprivation is mediated in part by the resulting secondary hyperaldosteronism. We show that experimental hyperaldosteronism, to levels seen with salt deprivation, causes an increase in the selective expression and activity of NHE3, an apically located isoform of the Na+/H+ exchange family that functions in transepithelial Na+ absorption. The effect of aldosterone on NHE3 expression is tissue specific, occurring in intestine and not in kidney. Within the intestine, these effects are regional, being observed only in proximal colon, and different in distribution from that observed with glucocorticoids, where the predominant effect occurs in ileum. Although glucocorticoids are well known to exert many effects via regulation of transcript levels, the present study demonstrates that aldosterone stimulates intestinal Na+ absorption by increasing cellular NHE3 expression, a response that is tissue and region specific.

Absorption↗
PubMed1998

A case of AV reentrant tachycardia due to a concealed accessory pathway with retrograde conduction manifested by isoproterenol.

Retrograde conduction of the concealed accessory pathway (AP) is a prerequisite for the induction of atrioventricular reentrant tachycardia (AVRT). In patients with AVRT due to a concealed AP, the absence of retrograde conduction of the AP in the baseline state has rarely been reported. We report a case of AVRT due to a concealed left lateral AP, in which the retrograde conduction was absent in the baseline state and manifested by isoproterenol infusion. A 61-year-old man had suffered from intermittent palpitation for 17 years. A narrow QRS complex tachycardia with a retrograde P wave in the ST segment was recorded in 24-h Holter monitoring. An electrophysiologic study was performed while he was in a nonsedated state. No ventriculoatrial conduction over either the normal atrioventricular conduction system or the AP was demonstrated in the baseline state. Isoproterenol was infused at a rate of 1.0 microg/min. Retrograde conduction over the AP became manifest and AVRT was induced. The AP was ablated with radiofrequency energy at the left free wall. After ablation of the AP, no tachycardia was induced. To the authors'best knowledge, only 1 other similar case has been reported in the literature.

Heart Conduction System↗
PubMed1998

Minimizing artifacts caused by metallic implants at MR imaging: experimental and clinical studies.

OBJECTIVE: The purpose of this study was to investigate the effect of metallic implant positioning on MR imaging artifacts, to determine the optimal imaging conditions for minimizing artifacts, and to show the usefulness of artifact-minimizing methods in imaging of the knee. MATERIALS AND METHODS: Using MR images of experimental phantoms (titanium alloy and stainless steel screws), we compared the magnitude of metal-induced artifacts for various pulse sequences, different imaging parameters for the fast spin-echo sequence, and different imaging parameters for several incremental angles between the long axis of the screw and the direction of the main magnetic field. In clinical MR imaging of knees with metallic implants (n = 19), we assessed geometric distortion of anatomic structures to compare the influence of different pulse sequences (n = 19), frequency-encoding directions (n = 7), and knee positions (n = 15). RESULTS: Titanium alloy screws consistently produced smaller artifacts than did stainless steel screws. In experimental MR studies, artifacts were reduced with fast spin-echo sequences, with a screw orientation as closely parallel to the main magnetic field as possible, and, particularly, with smaller voxels that correlated positively with artifact size (R2 = .88, p < .01). In clinical MR studies, fast spin-echo MR imaging obscured articular structures less than did spin-echo imaging (8/19 patients). In particular, the anterior-posterior frequency-encoding direction (3/7 patients) and the flexion position of the knee (5/15 patients) were effective in reducing artifacts. CONCLUSION: MR artifacts can be minimized by optimally positioning in the magnet subjects with metallic implants and by choosing fast spin-echo sequences with an anterior-posterior frequency-encoding direction and the smallest voxel size.

Adult↗
PubMed1998

The development of digital library system for drug research information.

The sophistication of computer technology and information transmission on internet has made various cyber information repository available to information consumers. In the era of information super-highway, the digital library which can be accessed from remote sites at any time is considered the prototype of information repository. Using object-oriented DBMS, the very first model of digital library for pharmaceutical researchers and related professionals in Korea has been developed. The published research papers and researchers' personal information was included in the database. For database with research papers, 13 domestic journals were abstracted and scanned for full-text image files which can be viewed by Internet web browsers. The database with researchers' personal information was also developed and interlinked to the database with research papers. These database will be continuously updated and will be combined with world-wide information as the unique digital library in the field of pharmacy.

Database Management Systems↗
PubMed1998

Pharmacokinetic analysis for assessing developmental toxicity of a new synthetic acetolactate synthase inhibitor, LGC-40863, in rats.

Effects of O-[2,6-bis[(4,6-dimethoxy-2pyrimidinyl)oxy]benzoyl]oxime (LGC-40863) on dams and embryonic development were examined at p.o. doses of 500, 1000 and 2000 mg/kg/day on days 6 to 15 of gestation in rats. No significant maternal or embryonic toxicity was observed at any of the doses. However, external fetal anomalies including brachycephaly, microcephaly, micrognathia, agnathia, lordosis and edema were observed at an incidence of 2.2% at the lowest dosage level but not at higher dosages. Because these malformations are not common as spontaneous variations in rats, we carried out a toxicokinetic study to clarify whether the fetal anomalies at 500 mg/kg are related to LGC-40863. During multiple p.o. administrations of LGC-40863 at the same doses used in the developmental toxicity study, LGC-40863 was not detected in the systemic circulation. Moreover, 3 months of multiple dosing did not alter its plasma level. In the pregnant rats receiving 500 mg/kg on 10 consecutive days of gestation, LGC-40863 was also undetectable. However, after i.v. administration, high levels of the drug were found in plasma, and these could be described by a two-compartment model. These results demonstrate that the bioavailability of LGC-40863 is negligible. To investigate a possible relevance of metabolite(s) to the fetal anomalies, we examined excretion of radioactivity after p.o. doses of 500 and 2000 mg/kg of LGC-40863 spiked with [14C]LGC-40863. For both doses, cumulative recovery up to 72 hr was approximately 80% and 9% in feces and urine, respectively, indicating dose linearity in the elimination kinetics. Overall, these toxicokinetic data suggest that the fetal anomalies observed at 500 mg/kg are not associated with LGC-40863 but are spontaneously generated. In conclusion, LGC-40863 had neither significant maternal nor developmental toxicity at any of the doses tested for p.o. exposure.

Abnormalities, Drug-Induced↗
PubMed1997

Oligomycin inhibits store-operated channels by a mechanism independent of its effects on mitochondrial ATP.

Inhibitors of mitochondrial oxidative metabolism have been proposed to interfere with Ca2+ influx mediated by store-operated channels (SOC), secondary to their effects on ATP production. We assessed SOC activity by 45Ca2+ influx and fluorimetric measurements of free Ca2+ or Mn2+ quench in thapsigargin-treated Chinese hamster ovary cells and Jurkat T-cells, and additionally by electrophysiological measurements of the Ca2+-release-activated Ca2+ current (Icrac) in Jurkat T-cells. Various mitochondrial antagonists were confirmed to inhibit SOC. However, the following evidence supported the proposal that oligomycin, in particular, exerts an inhibitory effect on SOC in addition to its known actions on mitochondria and Na+-pump activity: (i) the concentrations of oligomycin required to inhibit SOC-mediated Ca2+ influx or Icrac (half-inhibitory concentration approximately 2 microM) were nearly 50-fold higher than the concentrations that blocked mitochondrial ATP production; (ii) the rank order of potency of oligomycins A, B and C for decreasing SOC-mediated Ca2+ influx or Icrac differed from that known for inhibition of mitochondrial function; (iii) oligomycin blocked Icrac under voltage clamp and with intracellular Na+ and K+ concentrations fixed by dialysis from the patch pipette, arguing that the effect was not secondary to membrane polarization or pump activity; and (iv) fixing the cytosolic ATP concentration by dialysis from the patch pipette attenuated rotenone- but not oligomycin-mediated inhibition of Icrac. Oligomycin also blocked volume-activated Cl- currents, a profile common to some other known blockers of SOC that are not known mitochondrial inhibitors. These findings raise the possibility that oligomycin interacts directly with SOC, and thus may extend the known pharmacological profile for this type of Ca2+-influx pathway.

Adenosine Triphosphate↗
PubMed1997

Expression of HuD (a paraneoplastic encephalomyelitis antigen) mRNA in lung cancer.

HuD, one of the Hu antigens (HuD and HuC), was recognized in the sera of small cell lung cancer (SCLC) patients with antibody-associated paraneoplastic encephalomyelitis/peripheral sensory neuropathy (PEM/PSN). Three forms of HuD mRNA, 197, 156, 110 nucleotides are made by alternative splicing at 868-909 residues and an additional 3'-splice site. To determine the diagnostic value of the HuD expression for small cell lung cancer, we examined 4 SCLC cell lines, 9 surgically resected SCLCs, and 12 surgically resected non-SCLCs using the reverse transcriptase-polymerase chain reaction with the HuD-specific primer pairs that spanned the putative alternative 3'-splicing site and direct DNA sequencing. None of the patients were associated with PEM/PSN. A single RNA transcript (156 nucleotides) among three forms (110, 156, 197 nucleotides) of the HuD gene was an alternatively spliced at 868-909 residues in SCLC cell lines. Expression of the HuD gene was stronger in three classic cell lines, but not in a variant cell line. Two of 9 SCLCs (22%) and 3 of 12 non-SCLCs (25%) expressed only the major RNA transcript (156 nucleotides) of the HuD gene, which was alternatively spliced in the same fashion as the cell line. These results revealed that no aberrant alternative splicing occurred in SCLC not associated with PEM/PSN and the expression of HuD gene was not specific for a particular histologic subtype of human lung cancer.

Antigens, Neoplasm↗