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M K Cho

Publications and source records attributed to M K Cho.

At least 37 records · Page 2Linked to original sources
PubMed1999

Determination of members of a Borrelia afzelii-related group isolated from Ixodes nipponensis in Korea as Borrelia valaisiana.

The 16S rRNA sequences of the Korean Borrelia strains 5MT and 9MT, isolated from Ixodes nipponensis, showed identities of 99.0-99.1% to that of B. afzelii. The strains were tentatively classified as belonging to the B. afzelii-related group. In this study, Korean isolates, including these strains, were characterized further and compared with recently described new species. These strains generated a RFLP pattern that has not been found previously in RFLP analysis of the 5S-23S rRNA intergenic spacer and the flagellin gene. When phylogenetic trees were constructed, based on the 5S-23S rRNA intergenic spacer, flagellin gene and 16S rRNA sequences, these Korean isolates formed a cluster with the Borrelia strain Am501 isolated from Ixodes columnae in Japan and Borrelia valaisiana strains VS116T and UK isolated from Ixodes ricinus in Europe and were distinguishable from the other species. However, these three groups of strains were divergent from each other in the molecular masses of the putative outer surface protein A (OspA) and in the sequences of the ospA gene. These findings suggest that these Korean isolates and one Japanese isolate are members of B. valaisiana and that OspA of this species is divergent, as is that of Borrelia garinii. This led to the speculation that B. valaisiana strains are adapted to the vector ticks found in each locality.

Animals↗
PubMed1999

A fission yeast gene, him1(+)/dfp1(+), encoding a regulatory subunit for Hsk1 kinase, plays essential roles in S-phase initiation as well as in S-phase checkpoint control and recovery from DNA damage.

Saccharomyces cerevisiae CDC7 encodes a serine/threonine kinase required for G(1)/S transition, and its related kinases are present in fission yeast as well as in higher eukaryotes, including humans. Kinase activity of Cdc7 protein depends on the regulatory subunit, Dbf4, which also interacts with replication origins. We have identified him1(+) from two-hybrid screening with Hsk1, a fission yeast homologue of Cdc7 kinase, and showed that it encodes a regulatory subunit of Hsk1. Him1, identical to Dfp1, previously identified as an associated molecule of Hsk1, binds to Hsk1 and stimulates its kinase activity, which phosphorylates both catalytic and regulatory subunits as well as recombinant MCM2 protein in vitro. him1(+) is essential for DNA replication in fission yeast cells, and its transcription is cell cycle regulated, increasing at middle M to late G(1). The protein level is low at START in G(1), increases at the G(1)/S boundary, and is maintained at a high level throughout S phase. Him1 protein is hyperphosphorylated at G(1)/S through S during the cell cycle as well as in response to early S-phase arrest induced by nucleotide deprivation. Deletion of one of the motifs conserved in regulatory subunits for Cdc7-related kinases as well as alanine substitution of three serine and threonine residues present in the same motif resulted in a defect in checkpoint regulation normally induced by hydroxyurea treatment. The alanine mutant also showed growth retardation after UV irradiation and the addition of methylmethane sulfonate. In keeping with this result, a database search indicates that him1(+) is identical to rad35(+). Our results reveal a novel function of the Cdc7/Dbf4-related kinase complex in S-phase checkpoint control as well as in growth recovery from DNA damage in addition to its predicted essential function in S-phase initiation.

Amino Acid Sequence↗
PubMed1999

Extramammary Paget's disease with aggressive behavior: a report of two cases.

Extramammary Paget's disease (EMPD) is an intraepithelial neoplastic disorder which is included as a rare malignant condition. However, it sometimes shows aggressive behavior of local recurrence and coexisting malignancy. We had experienced nine cases of EMPD involving the scrotum for seven years. Two cases of them presented metastasis. The first case presented extensive inguinal lymph node metastasis with underlying adnexal adenocarcinoma one year after wide local excision. The second case initially presented multiple metastasis to the liver and in the lymph node. The latter, showing fulminant progression with liver metastasis, may be only the second case reported in English literature. EMPD is considered as a malignant neoplasm with aggressive behavior from initial presentation. Because wide local excision of the lesion alone may be occasionally insufficient, a careful follow-up must be done to detect recurrence or internal malignancy.

Aged↗
PubMed1999

Molecular basis for hepatic detoxifying enzyme induction by 2-(allylthio)pyrazine in rats in comparison with oltipraz: effects on prooxidant production and DNA degradation.

The expression of hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferases (GSTs) by 2-(allylthio)pyrazine (2-AP), an experimental chemopreventive agent, was investigated in rats. Northern blot analysis revealed that 2-AP caused increases in mEH, rGSTA2/3/5, and rGSTM1/2 mRNA levels. mEH and rGSTA2 proteins were also induced. Molecular basis of the enzyme induction by 2-AP was studied in comparison with oltipraz (Olt). Rats exposed to buthionine sulfoximine, a GSH-depleting agent, before treatment with either 2-AP or Olt exhibited greater increases in the mRNA levels than the individual treatment. Conversely, increases of the mRNAs were prevented by cysteine treatment, indicating that metabolic intermediates or reactive oxygens produced from the agents could be reduced by cysteine. Gel shift analysis revealed that nuclear factor-kappaB, which is associated with the altered cellular redox state, was not activated by the agents. Effects of these agents on the breakage of phix-174 DNA were compared in vitro. 2-AP effectively reduced the conversion of supercoiled DNA to the open circular form induced by benzenetriol and prevented benzenetriol- and iron-catalyzed degradation of DNA, whereas Olt failed to prevent strand breakage of DNA. These results provided evidence that: 1) 2-AP was effective in elevating the hepatic mEH and GST gene expression in rats, which might be mediated with the production of reactive oxygen species; 2) nuclear factor-kappaB activation was not involved in the induction of the detoxifying enzymes by either 2-AP or Olt in spite of their production of reactive oxygens in vivo; and 3) the antioxidant effect of 2-AP in vitro differed from that of Olt.

Animals↗
PubMed1998

Differential induction of rat hepatic microsomal epoxide hydrolase and rGSTA2 by diazines: the role of cytochrome P450 2E1-mediated metabolic activation.

Previous studies have shown that pyridazine (PD) and pyrazine (PZ) are efficacious in inducing microsomal epoxide hydrolase (mEH) in the liver with elevation of the mRNA level. The present study was designed to investigate the expression of mEH and rGSTA2 genes in response to the diazines including PD, PZ and pyrimidine (PM) and the basis for their enzyme induction. Rats treated with either PD or PZ for 3 days resulted in marked increases in mEH and rGSTA2 mRNA levels with concomitant induction of the proteins, whereas PM failed to elevate the mRNA levels. Treatment of rats with a single dose of PD or PZ showed dose-dependent increases in mEH and rGSTA2 mRNA levels at 24 h with ED50 values being approximately 10 mg/kg. Time-course studies showed that the mRNA levels were increased to maximal extents at 24-48 h after treatment. Studies were extended to assess the mechanistic basis for the enzyme induction by PD and PZ. beta-Naphthoflavone (BNF) caused a 6-fold increase of rGSTA2 mRNA in the liver (100 mg/kg per day, p.o., 3 days), as compared to control, whereas the agent failed to increase mEH mRNA level. Administration of PD or PZ (50 mg/kg) to BNF-pretreated rats resulted in no enhanced increase of the mEH mRNA as compared to the individual treatment, while the rGSTA2 mRNA level was additively elevated, suggesting the possibility that increases of the mEH and rGSTA2 mRNAs by PD or PZ might be mediated with antioxidant responsive element(s) in the genes, but not with xenobiotic responsive element. Western blot analysis revealed that cytochrome P450 2E1 was induced 3- to 4-fold by both PD and PZ, whereas PM failed to induce P450 2E1. Concomitant treatment of rats with PD or PZ in combination with acetone, a substrate for P450 2E1, caused no significant increase in the mEH and rGSTA2 mRNA levels relative to that in untreated animals, whereas PD or PZ treatment without a concomitant acetone administration resulted in marked increases of the mRNAs. Diazine-inducible mEH and rGSTA2 mRNA levels were approximately 2-fold enhanced in P450 2E1-induced starved rats, as compared to those in diazine-treated unstarved animals. These data indicate that P450 2E1-mediated bioactivation of the diazines might contribute to transcriptional activation of the mEH and GST genes. These results provide evidence that both PD and PZ efficaciously induce mEH and rGSTA2 in the liver with increases in the mRNA levels, while PM is ineffective, and that induction of mEH and rGSTA2 may be mediated through bioactivation of the diazines by P450 2E1.

Acetone↗
PubMed1998

Does masking author identity improve peer review quality? A randomized controlled trial. PEER Investigators.

CONTEXT: All authors may not be equal in the eyes of reviewers. Specifically, well-known authors may receive less objective (poorer quality) reviews. One study at a single journal found a small improvement in review quality when reviewers were masked to author identity. OBJECTIVES: To determine whether masking reviewers to author identity is generally associated with higher quality of review at biomedical journals, and to determine the success of routine masking techniques. DESIGN AND SETTING: A randomized controlled trial performed on external reviews of manuscripts submitted to Annals of Emergency Medicine, Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology. INTERVENTIONS: Two peers reviewed each manuscript. In one study arm, both peer reviewers received the manuscript according to usual masking practice. In the other arm, one reviewer was randomized to receive a manuscript with author identity masked, and the other reviewer received an unmasked manuscript. MAIN OUTCOME MEASURE: Review quality on a 5-point Likert scale as judged by manuscript author and editor. A difference of 0.5 or greater was considered important. RESULTS: A total of 118 manuscripts were randomized, 26 to usual practice and 92 to intervention. In the intervention arm, editor quality assessment was complete for 77 (84%) of 92 manuscripts. Author quality assessment was complete on 40 (54%) of 74 manuscripts. Authors and editors perceived no significant difference in quality between masked (mean difference, 0.1; 95% confidence interval [CI], -0.2 to 0.4) and unmasked (mean difference, -0.1; 95% CI, -0.5 to 0.4) reviews. We also found no difference in the degree to which the review influenced the editorial decision (mean difference, -0.1; 95% CI,-0.3 to 0.3). Masking was often unsuccessful (overall, 68% successfully masked; 95% CI, 58%-77%), although 1 journal had significantly better masking success than others (90% successfully masked; 95% CI, 73%-98%). Manuscripts by generally known authors were less likely to be successfully masked (odds ratio, 0.3; 95% CI, 0.1-0.8). When analysis was restricted to manuscripts that were successfully masked, review quality as assessed by editors and authors still did not differ. CONCLUSIONS: Masking reviewers to author identity as commonly practiced does not improve quality of reviews. Since manuscripts of well-known authors are more difficult to mask, and those manuscripts may be more likely to benefit from masking, the inability to mask reviewers to the identity of well-known authors may have contributed to the lack of effect.

Authorship↗
PubMed1998

Masking author identity in peer review: what factors influence masking success? PEER Investigators.

CONTEXT: In a previous study, we found that masking success was higher at a journal that masked reviewers to author identity. We hypothesized that masking policy or other factors could be associated with masking success. OBJECTIVES: To evaluate differences in success of masking reviewers to author identity at 7 biomedical journals and to identify factors associated with these differences. DESIGN: Written questionnaire. PARTICIPANTS: Reviewers at 3 journals with a long-standing policy of masking author identity (Annals of Emergency Medicine, Epidemiology, and Journal of the American Geriatrics Society) and 4 journals without a policy of masking author identity (Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology). MAIN OUTCOME MEASURES: Masking success (percentage of reviewers successfully masked) and reviewer characteristics associated with masking. RESULTS: There was no significant difference in masking success between journals with a policy of masking (60%) and those without (58%) (P= .92). We found no association between masking success and a policy of masking when adjusted for the reviewer characteristics of age, sex, years of reviewing experience, number of articles published, number of articles reviewed, percentage of time spent in research, editorial experience, or academic rank (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.64-2.8; P=.43). In multivariable analysis of reviewer characteristics, reviewers spending a greater percentage of time in research, the only significant predictor of masking success, were less likely to be successfully masked (OR, 1.01; 95% CI, 1.00-1.02) (P=.04). CONCLUSIONS: Masking success appears unrelated to a journal policy of masking, but is associated with reviewers' research experience and could be affected by other characteristics. Using reviewers with less research and reviewing experience might increase masking success, but the effect on review quality is unknown.

Authorship↗
PubMed1998

Infection rate of Leptospira interrogans in the field rodent, Apodemus agrarius, in Korea.

Leptospirosis has significantly decreased in Korea since 1988, following the leptospiral vaccination programme initiated in 1988. Whether this wholly explains the decreased incidence is uncertain. As an initial step to answer this question, infection rates of Leptospira interrogans in field rodents, Apodemis agrarius, were examined and compared with previous data. Two hundred and twenty-two A. agrarius were captured during October-December 1996. Spirochaetes were isolated from 22 (9.9%) and leptospiral DNA was detected in an additional 6 rodents (12.6%). Subsequent microscopic agglutination tests (MAT) classified all these isolates as L. interrogans serogroup Icterohaemorrhagiae serovar lai. The above data did not significantly differ from previous surveys in 1984-7. There was no significant change of L. interrogans infection in field rodents following the introduction of the vaccination programme in Korea. Further studies are needed to determine the role of human vaccination in reducing incidence.

Animals↗
PubMed1997

Educational material about genetic tests: does it provide key information for patients and practitioners?

Genetic testing for common conditions will be used increasingly in primary care, but resources for patient counseling are decreasing. It is also necessary that primary care practitioners be better equipped to do basic genetic counseling. Therefore, the quality of informational materials for practitioners and patients is important. It was unknown how often key elements recommended by policy groups were actually included in such material. It was our aim to determine the content of printed informational material for practitioners and patients on genetic testing. We performed (1) a telephone survey of organizations in the United States that developed genetic tests or services and (2) a content analysis of pamphlets obtained from these organizations to determine the presence of 10 critical elements necessary to evaluate the appropriateness and performance of the tests. Almost 95% (169/178) of organizations responded to our survey; 131/169 (78%) reported using informational materials. We analyzed 115 pamphlets collected from 125/131 (95%) organizations. Elements least frequently included in the pamphlets were risks and benefits, patient rights, and intended use or purpose of the test. Most frequently included were descriptions of the conditions detected by the test, and the appropriate patients for testing. Nearly one half of the pamphlets included some statement about the accuracy of the test, but most of these did not specify whether their statements referred to sensitivity, specificity, or predictive value. Overall, pamphlets tended to contain information that would aid in determining a patient's eligibility for a genetic test, but did not contain sufficient information about the tests themselves. Our results suggest that several critical elements need to be added to enhance informed choices by patients and physicians.

Benchmarking↗
PubMed1997

Characterization of viral inhibitory substance released from fused splenocyte.

The D variant of the encephalomyocarditis (EMC-D) virus is diabetogenic in mice by infecting and destroying pancreatic beta cells, but the EMC-B and EMC-DV viruses are not diabetogenic. We have presumed that the nondiabetogenicity of EMC-B and EMC-DV is mainly caused by release of some viral inhibitory factors from lymphocytes or phagocytic cells. Mice were infected with EMC-B and their splenocytes were fused with myeloma cells. The splenocyte hybridoma 12D8 releases the viral inhibitory substance (VIS) which is neither immunoglobulin nor interferon. VIS has inhibitory effects against EMC-D in several kinds of cell lines, and against EMC-D, EMC-B, coxsackie B4, reovirus and the vesicular stomatitis virus in the L cell. VIS has a strong preventive effect (100%) against EMC-D induced diabetes in SJL/J mice and DBN/2N mice. In both pre- and post-treatment studies, VIS remarkably decreased the incidence of both illness and death in SJL/J mice infected with the EMC-D virus. VIS, culture supernate itself of hybridoma, had viral inhibitory activities equivalent to 10(6)-10(7) IU/ml of interferon. VIS was very labile to heat (75% loss of activities at 37 degrees C for 18 h), stable only at pH 5-9, and precipitated at 50% (NH4)2SO4 solution. VIS activities existed in supernatant and pellet prepared from ultracentrifugation, but the properties of their activities could be differentiated quantitatively and qualitatively. It is speculated that VIS may be composed of at least two factors even though interferon may partially participate in one component of supernatant. The prevention and treatment effect of VIS on EMC-D infection in SJL/J mice might be due to the inhibition of the virus replication by VIS.

Animals↗
PubMed1997

Long-term oral administration of ginseng extract decreases serum gamma-globulin and IgG1 isotype in mice.

Effects of long-term oral administration of ginseng extract on serum protein profile and immunoglobulin (Ig) isotypes were studied in mice. Ginseng extract was orally administered to healthy female mice for 52 days at doses of 30 and 150 mg/kg per day and serum protein electrophoretograms and Ig isotypes levels were evaluated. Serum level of gamma-globulin was decreased dose dependently to 82% (P < 0.05) and 56% (P < 0.01) of control values at the doses of 30 and 150 mg/kg per day, respectively. Levels of total protein, albumin, alpha2- and beta-globulin fractions, as well as the ratio of albumin to globulin (A/G) did not change significantly. However, the alpha1-globulin level increased by 24% (P < 0.05) at the doses of 30 and 150 mg/kg per day. Among the Ig isotypes, including IgG1, IgG2a, IgG2b, IgG3, IgM and IgA, serum IgG1 was dose dependently decreased to 68% (P < 0.05) of control values at the dose of 150 mg/kg per day without significant changes in other Ig isotypes. As IgG1 isotype is rarely cytotoxic and can act as a blocking antibody, it is suggested that the selective decrease in serum IgG1 induced by ginseng extract without changes in the cytotoxic antibodies such as IgG2a may be helpful for the prevention and inhibition of cancer.

Administration, Oral↗
PubMed1996

Expression of glutathione S-transferases Ya, Yb1, Yb2, Yc1 and Yc2 and microsomal epoxide hydrolase genes by thiazole, benzothiazole and benzothiadiazole.

The effects of thiazole (TH), benzothiazole (BT) and benzothiadiazole (BZ) on the expression of hepatic glutathione S-transferases (GSTs) Ya, Yb1, Yb2, Yc1 and Yc2 and microsomal epoxide hydrolase (mEH) genes were compared in rats. TH treatment resulted in 4- to 24-fold increases in GST Ya mRNA levels at 24 hr posttreatment; the ED50 value was 70 mg/kg. GST Ya mRNA levels were elevated 13-, 20-, 20- and 9-fold at 12, 24, 48 and 72 hr following 100 mg/kg of TH treatment, respectively, as compared with the control. BT was a moderate inducer of GST Ya with a maximal 18-fold increase observed, whereas BZ treatment caused a transient increase in GST Ya mRNA at 12 hr posttreatment, followed by a return to a 4-fold relative increase at 24 hr or afterward. Treatment of rats with TH at the dose of 100 mg/kg resulted in an approximately 10-fold increase in either Yb1 or Yb2 mRNA levels at 24 hr posttreatment. BT-treated rats showed 7- and 3-fold increases in the GST subunit Yb1 and Yb2 mRNA levels at 24 hr posttreatment. BZ was the least effective in modulating either GST Yb1 or Yb2 mRNA, resulting in < 2-fold changes. GST Yc1 and Yc2 mRNA levels were increased approximately 8-fold at the dose of 200 mg/kg of TH. BT minimally affected GST subunit Yc1 and Yc2 mRNA levels, with a maximal 4-fold relative increase observed. BZ was the least effective in enhancing Yc1 and Yc2 mRNA levels. Protein levels for GST subunit Ya, Yb1, Yb2 and Yc were also elevated in response to TH by 3-, 2-, 2-, and 2-fold, respectively. Thus, TH was effective in modulating both constitutive and inducible GST gene expression. BT or BZ was much less effective in increasing the expression of GST subunits. These RNA and Western blot analyses revealed that the levels of major GST were differentially increased after treatment with these thiazoles, exhibiting a rank order of GST expression of TH > BT > BZ. mEH expression by these compounds appeared to be consistent with that of GST Ya. The mRNA levels for GST Ya, Yb1, Yb2, Yc1 and Yc2 and mEH were also determined after treatment with triazole (TR), imidazole (IM), benzoxazole (BX), benzotriazole (BTR) or benzimidazole (BIM). TR, IM, BX or BTR caused increases in Ya, Yb1, Yc1 and Yc2 mRNA levels by 2- to 3-fold, whereas the agents failed to modulate the expression of GST Yb2. The fact that benzene, cyclohexane or n-hexane minimally affected the major GST or mEH mRNA levels provided evidence that certain heterocyclic compounds are more capable of modulating GST or mEH gene expression than hydrocarbons. These results corroborate evidence that the thiazoles differentially stimulate GST or mEH genes, with TH being the most efficacious; that thiazoles with carbocyclic ring are much less effective in increasing GST or mEH levels than is TH; and that the changes in these GST and mEH levels are primarily associated with increases in mRNA levels.

Animals↗