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Biomedical subjects

M J Cho

Publications and source records attributed to M J Cho.

At least 91 records · Page 5Linked to original sources
PubMed1996

Macromolecular versus small-molecule therapeutics: drug discovery, development and clinical considerations.

Recent advances in biomedical science in general, and molecular biology in particular, have provided a greater understanding of pathogenesis at the molecular and (sub)cellular level. In turn, this has stimulated the development of macromolecular, mechanism-based therapeutic agents, ranging from recombinant proteins, to oligonucleotides, to genes/gene fragments. The factors essential for the successful development of this new class of therapeutic agents are not necessarily the same as those for the development of conventional small organic molecules. This review mentions several issues relating to the development of macromolecular drugs, and emphasizes the key issue of drug transport and delivery.

Biotechnology↗
PubMed1996

Enhancement of radiation effect by Ginkgo biloba extract in C3H mouse fibrosarcoma.

BACKGROUND AND PURPOSE: Ginkgo biloba leaf extract (GBE) is known to increase peripheral blood circulation. The hypothesis that GBE may be able to enhance radiosensitivity of tumor by improving tumor blood flow and thus decreasing hypoxic fraction was tested. MATERIALS AND METHODS: Fibrosarcoma (FSaII) growing in C3H mouse leg muscle was used as a tumor model. GBE was given i.p. 1 h before irradiation with or without priming dose given 1 day earlier. Effect on tumor and normal tissue radiation reaction was investigated. RESULTS: Tumor growth delay by radiation was more elongated after two doses (1-day interval) of GBE than after a single dose. Radiation dose for 3-day tumor growth delay was decreased from 12.45 (10.97-13.93) Gy to 6.06 (3.89-8.22) Gy by two doses of GBE [enhancement ratio = 2.06 (1.32-2.79)]. Hypoxic cell fraction was 10.6% (6.3-18.2%) for control, 7.2% (3.8-14.0%) after a single dose (P = 0.18) and 2.7% (1.5-5.0%) after two doses (P < 0.001). Radiation effect on normal tissue, estimated by acute skin reaction and jejunal crypt assay, was not affected by GBE. CONCLUSION: Ginkgo biloba extract enhances radiation effect on tumor without increasing acute normal tissue radiation damage in this model system probably by increasing tumor blood flow and further investigation for this possible radiosensitizer is needed.

Animals↗
PubMed1996

Expressed sequence tags of Chinese cabbage flower bud cDNA.

We randomly selected and partially sequenced cDNA clones from a library of Chinese cabbage (Brassica campestris L. ssp. pekinensis) flower bud cDNAs. Out of 1216 expressed sequence tags (ESTs), 904 cDNA clones were unique or nonredundant. Five hundred eighty-eight clones (48.4%) had sequence homology to functionally defined genes at the peptide level. Only 5 clones encoded known flower-specific proteins. Among the cDNAs with no similarity to known protein sequences (628), 184 clones had significant similarity to nucleotide sequences registered in the databases. Among these 184 clones, 142 exhibited similarities at the nucleotide level only with plant ESTs. Also, sequence similarities were evident between these 142 ESTs and their matching ESTs when compared using the deduced amino acid sequences. Therefore, it is possible that the anonymous ESTs encode plant-specific ubiquitous proteins. Our extensive EST analysis of genes expressed in floral organs not only contributes to the understanding of the dynamics of genome expression patterns in floral organs but also adds data to the repertoire of all genomic genes.

Cloning, Molecular↗
PubMed1996

Structure of the 3' terminus of the hepatitis C virus genome.

Hepatitis C virus (HCV), a positive-strand RNA virus, has been considered to have a poly(U) stretch at the 3' terminus of the genome. We previously found a novel 98-nucleotide sequence downstream from the poly(U) stretch on the HCV genome by primer extension analysis of the 5' end of the antigenomic-strand RNA in infected liver (T. Tanaka, N. Kato, M.-J. Cho, and K. Shimotohno, Biochem. Biophys. Res. Commun. 215: 744-749, 1995). Here, we show that the novel sequence is a highly conserved 3' tail of the HCV genome. We repeated primer extension analyses with four HCV-infected liver samples and found the 98-nucleotide sequence in all the samples. Furthermore, experiments in which RNA oligonucleotide was ligated to the 3' end of the HCV genome existing in infectious serum revealed nearly identical 3' termini with no extra sequence downstream from the 98-nucleotide sequence, suggesting that this sequence is the tail of the HCV genome. This tail sequence was highly conserved among individuals and even between the two most genetically distant HCV types, II/1b and III/2a. Computer modeling predicted that the tail sequence can form a conserved stem-and-loop structure. These results suggest that the novel 3' tail is a common structure of the HCV genome that plays an important role in initiation of genomic replication.

Base Sequence↗
PubMed1996

Pathogenesis and prevention of stomach cancer.

In many Western developed countries, the incidence of stomach cancer has declined dramatically. This decrease was an extraordinary, "unplanned triumph", especially when compared to other cancers. Stomach cancer is still the most prevalent malignant tumor in Korea. Most Koreans carry Helicobacter pylori in their stomach. Thus, a new hypothesis, based on the relationship between the host and Helicobacter pylori, is presented as the carcinogenesis of human stomach cancer. The reasons for why the N-nitrosamide hypothesis should be dismissed as the etiology of stomach cancer, and why the contemporarily available principles and practice of intervention strategies to rapidly decrease the surprisingly high prevalence rate of Helicobacter pylori infection are impractical at this moment, are explained. In order to introduce an alternative provisional strategy of the "planned triumph" for the population vulnerable to stomach cancer, vitamin C is defined as an anti-inflammatory agent on the basis of the pathogenesis of Helicobacter pylori infection.

Animals↗
PubMed1995

Molecular cloning and functional characterization of a cDNA encoding nucleosome assembly protein 1 (NAP-1) from soybean.

NAP-1, a protein first isolated from mammalian cells, can introduce supercoils into relaxed circular DNA in the presence of purified core histones. Based on its in vitro activity, it has been suggested that NAP-1 may be involved in nucleosome assembly in vivo. We isolated a cDNA clone encoding a soybean NAP-1 homolog, SNAP-1. The SNAP-1 cDNA contains an open reading frame of 358 amino acids residues with a calculated molecular weight of 41 kDa. The deduced amino acid sequence of SNAP-1 shares sequence similarity with yeast NAP-1 (38%) and human hNRP (32%). Notable features of the deduced sequence are two extended acidic regions thought to be involved in histone binding. SNAP-1 expressed in Escherichia coli induces supercoiling in relaxed circular DNA, suggesting that SNAP-1 may have nucleosome assembly activity. The specific activity of SNAP-1 is comparable to that of HeLa NAP-1 in an in vitro assay. Western analysis reveals that SNAP-1 is expressed in the immature and young tissues that were examined, while mature tissues such as old leaves and roots, show very little or no expression. NAP-1 homologs also appear to be present in other plant species.

Amino Acid Sequence↗
PubMed1995

A novel sequence found at the 3' terminus of hepatitis C virus genome.

The 3' end region of positive-strand RNA-virus genomes is implicated in the initiation of genomic replication. We analyzed the extreme 3' end of the hepatitis C virus (HCV) genome by primer extension of the 5' end region of the antigenomic strand RNA found in infected liver. We discovered a novel sequence present downstream of the poly(U) stretch that was previously considered to be the 3' end structure of the HCV genome. The novel sequence was 98 nucleotides long and had no significant homology with any known sequences, viral or nonviral. The discovery of this novel tail on the HCV genome should contribute to the study of HCV replication.

Base Sequence↗
PubMed1995

Genotype distribution and comparison of the putative envelope region of hepatitis C virus from Korean patients.

Comparative nucleotide sequence studies of the genomes of hepatitis C virus (HCV) revealed that there are at least 6 different genotypes of HCV. The prevalence of HCV genotypes among the patients with liver diseases in Korea was investigated using the polymerase chain reaction (PCR) for the NS5 region. In the 75 HCV RNA positive samples, two genotypes, type 1b and type 2a, were the major causative agents which accounted for 60% and 33% of infections respectively, while 7% could not be assigned a genotype by the methods used. The nucleotide sequences of cDNAs encoding the putative envelope proteins from 10 type 1b and 5 type 2a genotype samples were analyzed. Approximately 31-42% of the nucleotide sequences of type 1b samples examined differed from those of different genotypes. In the case of type 2a samples, 36-42% of the nucleotide sequences differed from those of different genotypes. The diversities of the amino acid sequences were the same or greater than those of the nucleotide sequences. Two hypervariable regions (HVR1 and HVR2) were recognized in both HCV genomes of genotypes 1b and 2a. However, the sequence divergence within the HVR2 region of genotype 2a was less than that of genotype 1b.

Amino Acid Sequence↗
PubMed1995

Frequent in-frame length variations are found in the diverged simple repeat sequences of the protein-coding regions of two putative protein kinase genes of Brassica napus.

Two putative protein kinase cDNA clones were isolated from Brassica napus by screening with a putative protein kinase cDNA clone of Arabidopsis thaliana. The deduced amino acid sequences show a distinct modular composition, consisting of a possible protein kinase catalytic region at the amino terminus and a highly acidic region encoded from diverged simple repeat sequences at the carboxy terminus. Comparison of the nucleotide sequences encoding this acidic region revealed a high rate of in-frame length variation, while preserving the acidic characteristics. Similar variation is also found in the noncoding regions of these clones.

Amino Acid Sequence↗
PubMed1995

Molecular cloning and characterization of RGA1 encoding a G protein alpha subunit from rice (Oryza sativa L. IR-36).

A cDNA clone, RGA1, was isolated by using a GPA1 cDNA clone of Arabidopsis thaliana G protein alpha subunit as a probe from a rice (Oryza sativa L. IR-36) seedling cDNA library from roots and leaves. Sequence analysis of genomic clone reveals that the RGA1 gene has 14 exons and 13 introns, and encodes a polypeptide of 380 amino acid residues with a calculated molecular weight of 44.5 kDa. The encoded protein exhibits a considerable degree of amino acid sequence similarity to all the other known G protein alpha subunits. A putative TATA sequence (ATATGA), a potential CAAT box sequence (AGCAATAC), and a cis-acting element, CCACGTGG (ABRE), known to be involved in ABA induction are found in the promoter region. The RGA1 protein contains all the consensus regions of G protein alpha subunits except the cysteine residue near the C-terminus for ADP-ribosylation by pertussis toxin. The RGA1 polypeptide expressed in Escherichia coli was, however, ADP-ribosylated by 10 microM [adenylate-32P] NAD and activated cholera toxin. Southern analysis indicates that there are no other genes similar to the RGA1 gene in the rice genome. Northern analysis reveals that the RGA1 mRNA is 1.85 kb long and expressed in vegetative tissues, including leaves and roots, and that its expression is regulated by light.

Adenosine Diphosphate Ribose↗
PubMed1995

Effects of inclusion complexation on the transepithelial transport of a lipophilic substance in vitro.

Poor oral bioavailability of three experimental compounds, 1-III, observed in animals has been attributed to the low intrinsic solubility. To enhance their GI absorption, we attempted to increase the solubility of these compounds with hydroxypropyl beta-cyclodextrin (HPB)4 and gamma-cyclodextrin (HPG). Compound I showed an increase in solubility over 1,000-fold with 25% HPB at 25 degrees C. The association constant of the 1:1 complex between I and HPB was determined by phase-solubility analysis. Thermodynamic parameters involved were all favorable for the complexation. The large positive delta S degrees observed suggests that the complex formation is driven by a hydrophobic interaction. Apical-to-basal transport of I across the Madin Darby canine kidney (MDCK) cell monolayer was studied at 37 degrees C in the presence of HPB with or without agitation. The complex itself did not pass through the cell layer. Diffusion of the unbound I as well as the complex through the aqueous boundary layer in the apical side is rate-limiting. Regardless of hydrodynamics, decreasing HPB concentration at a given drug concentration increased the transport rate. The findings indicate that the transepithelial transport is attributed to the passive diffusion of available free drug molecules rather than the collision complex transfer at the cell surface.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1995

Isolation of two soybean G-box binding factors which interact with a G-box sequence of an auxin-responsive gene.

G-box binding factors (GBFs) constitute a family of plant DNA-binding proteins that bind to the G-box motif, a regulatory cis element present in many plant genes with a palindromic DNA motif of CACGTG. Previously TCCACGTGTC, a G-box motif, from an auxin responsive gene GmAux28 has been identified as a sequence-specific protein-binding site. Here the isolation of two soybean cDNA clones, referred to as SGBF-1 and SGBF-2, encoding proteins which bind to the G-box motif is reported. The primary structure of SGBF-1 and SGBF-2 predicts that these proteins contain a basic leucine zipper (bZIP) DNA-binding domain and an N-terminal proline-rich domain. A dramatic difference in the pattern of protein-DNA complex formation was observed when recombinant SGBF-1 and SGBF-2 proteins were analyzed by electrophoretic mobility shift assays (EMSAs). The SGBF-1 binding pattern obtained with the G-box probe resulted in three major retarded bands while the SGBF-2 formed a single complex. This shows that the characteristically diffuse banding pattern of plant nuclear proteins interacting with the G-box is also observed in a binding assay using only one recombinant GBF. EMSAs were performed with a few selected binding sequences to study the effect of flanking nucleotides to the hexanucleotide G-box core motif. The binding specificity of the SGBF proteins resembles that described for type A cauliflower nuclear G-box binding proteins which bind class I G-box elements [(G/T)(C/A)CACGTG(G/T)(A/C)]. Phylogenetic analysis of 13 GBF-like proteins from various plant species reveals that the SGBF-1 and SGBF-2 proteins belong to different lineages, suggesting that they may have distinct functions in activating transcription.

Amino Acid Sequence↗
PubMed1995

Reliability of the ICD-10 diagnostic criteria for research in mental disorders in the Republic of Korea.

The interrater reliability, confidence and ease of use of ICD-10 diagnostic criteria for research were assessed in the Republic of Korea as part of the field trials of World Health Organization collaborative study. A total of 279 patients were diagnosed according to the ICD-10 diagnostic criteria for research. Interrater reliability, calculated by kappa statistics, was found to be between 0.74 and 0.91 on 2-character categories and between 0.64 and 0.90 on 3-character categories except schizotypal disorder (F21). On the 4-character categories, the agreement in the affective states between raters was lower. The reasons are discussed based on cultural differences.

Adolescent↗
PubMed1995

NS3-4A of hepatitis C virus is a chymotrypsin-like protease.

The polyprotein encoded by a single open reading frame of hepatitis C virus (HCV) is processed by host- and virus-encoded proteases. The viral protease NS3 is responsible for the cleavage of at least four sites (NS3/4A, NS4A/4B, NS4B/5A, and NS5A/5B junctions) in the nonstructural protein region. To characterize the protease function of NS3 and NS4 on various target sites, efficient cis- and trans-cleavage assay systems were developed by using in vitro transcription and translation. Deletion of the C-terminal two-thirds from NS3 in an NS3-NS4A-4B polypeptide (NS3 delta C-4A-4B) hampered cleavage of the NS3/4A junction but not that of the NS4A/4B junction. As a consequence, expression of NS3 delta C-4A-4B containing an internal deletion of NS3 results in an NS3 delta C-4A fusion protein. NS3 delta C-4A shows very efficient and specific trans-cleavage activity at NS4A/4B, NS4B/5A, and NS5A/5B junctions. In addition, the biochemical properties of HCV NS3 delta C-4A were further elucidated by adding known protease inhibitors in trans-cleavage reactions. The HCV protease NS3-4A is inhibited by chymotrypsin-specific inhibitors N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), chymostatin, and Pefabloc SC but not by trypsin-like protease inhibitors antipain, leupeptin, and N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) or by the protease inhibitors E-64, bestatin, pepstatin, and phosphoramidon. This finding strongly suggests that HCV protease NS3-4A is a chymotrypsin-like serine protease.

Base Sequence↗
PubMed1994

Isolation and characterization of two beta-tubulin cDNA clones from rice.

Two cDNA clones encoding two different beta-tubulins, RTUB-1 and RTUB-2, were isolated from a rice cDNA library and their nucleotide sequences were analyzed. The deduced amino acid sequences showed amino acid sequence identity between 92% and 97% with other plant beta-tubulins. Southern blot analysis using gene-specific and coding-region probes suggested that beta-tubulins in rice are encoded by multigene families. The two cDNA clones represent two subfamilies of rice tubulins, RTUB-1 and RTUB-2, consisting of 3 to 4 genes and a single gene, respectively. The transcript levels of RTUB-1 and RTUB-2 genes were higher in actively elongating tissues such as etiolated shoot tissues and light-grown root tissues of four-day old seedlings.

Amino Acid Sequence↗
PubMed1994

Isolation and characterization of three soybean extensin cDNAs.

We have characterized three different soybean (Glycine max) mRNAs that encode apoproteins of extensins, a family of cell wall hydroxyproline-rich glycoproteins (HRGPs). These transcripts encoded distinctive Tyr-rich proteins containing characteristic Ser-Pro4 sequences organized in higher-order repetitive units. The first transcript encoded an extensin SbHRGP-1 containing the 16-amino acid repeat Ser-Pro4-Ser-Pro-Ser-Pro4-Tyr-Val-Tyr-Lys, with Val occasionally replaced by Ile or Tyr. The second transcript encoded the SbHRGP-2 protein containing the 16-amino acid repeat Ser-Pro4-Ser-Pro-Ser-Pro4-Tyr-Tyr-Tyr-Lys/His. The third transcript encoded the SbHRGP-3 protein containing a variant of 9- or 10-amino acid canonical repeats: Ser-Pro4-Tyr-Lys-Tyr-Pro, Ser-Pro5-Tyr-Lys-Tyr-Pro, and Ser-Pro4-Val-Tyr-Lys-Tyr-Lys, respectively. The dramatic amino acid substitutions in the Tyr-rich blocks (Tyr-X-Tyr-Lys) among these HRGPs indicate that each SbHRGP may have a different function in cell wall architecture.

Amino Acid Sequence↗