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M Y Kim

Publications and source records attributed to M Y Kim.

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

The effects of outcome misclassification and measurement error on the design and analysis of therapeutic equivalence trials.

In any clinical trial, the use of imperfect diagnostic procedures or laboratory techniques may lead to misclassification and measurement error in the primary outcome. Although the effects of non-differential outcome misclassification and measurement error on conventional superiority trials have been extensively investigated, less is known about the impact of these errors on the results and interpretation of therapeutic equivalence trials. In this paper we formally investigate the effects of outcome misclassification and measurement error on the estimates of treatment effects, type I error rate, and power of equivalence trials. Our results indicate that, contrary to what one may expect based on the well known attenuating effects of non-differential error in conventional studies, these errors do not always favour the goal of demonstrating equivalence. The magnitude and direction of the influence depend on a number of factors including the nature of the outcome variable, specific formulation of equivalence, size of the error rates, and assumptions regarding the true treatment effect.

Estrogen Replacement Therapy↗
PubMed2001

Expression profile of nine novel genes differentially expressed in hepatitis B virus-associated hepatocellular carcinomas.

Chronic hepatitis B virus (HBV) infection is known to be one of the major causes in the development of hepatocellular carcinoma (HCC), although the biomolecular mechanism(s) involved remain unclear. To identify the cellular gene(s) involved in HBV-associated hepatocarcinogenesis, we used the mRNA differential display method and examined three paired tumor and nontumor tissues, all of which had chromosomally integrated HBV-DNA through chronic infection. Using 240 different combinations of three one-base anchored oligo-dT primers and 80 arbitrary 13-mers, genes decreased or increased in expression more than twofold between each tumor tissue and its paired nontumor tissue were identified. Twenty-nine known genes and four novel genes were differentially over-expressed in the HCC tumor tissues. In contrast, 27 known genes and five novel genes were under-expressed in those tumor tissues. The nucleotide sequences of the nine novel gene fragments were determined and their expression patterns were examined in 40 HCC samples. HA61T2, PT18, HG63T1, and HG57T1 were preferentially over-expressed in 32 cases (80%, P<0.001), 24 cases (60%), 23 cases (57.5%) and 22 cases (55%) of the 40 tumor tissues, respectively. There was an increased frequency of HG57T1 over-expression in HCC patients with HBV-positive serology and low serum alpha-feto protein (AFP) levels (P<0.05). DNT10, PT8, PT19, ENT25 and HA6T4 were under-expressed in 26 cases (65%), 23 cases (57.5%), 21 cases (53%), 20 cases (50%) and 18 cases (45%) of the 40 tumor samples, respectively. There was a strong correlation of DNT10 under-expression with high serum AFP level in HCC patients, irrespective of HBV serology (P<0.01). HA6T4 was preferentially under-expressed in HCC tumors in patients with HBV-positive serology and high serum AFP levels (P<0.05). Thus, the functional analyses of the known and novel genes identified in this study should prove valuable to further understand the mechanism(s) of hepatocarcinogenesis.

Base Sequence↗
PubMed2001

Characterization of a novel allele of glucose oxidase from a Korean wild type strain of Aspergillus niger.

We have identified a novel allele of the glucose oxidase (GO, EC1.1.3.4) gene (GO) from a Korean wild type strain of Aspergillus niger, ACMO4, with an increased GO activity in culture filtrate. Southern blot analyses of GO from ACMO4 (GO-ACMO4) revealed that the gene was present as a single copy in the genome of A. niger. However, its sequence differs from that of GO from A. niger ATCC 9029 (GO-ATCC9029). GO-ACMO4 appears to be a functional gene based on the fact that it is enzymatically active when heterologously expressed in yeast. Sequence comparisons of the coding region of GO-ACMO4 revealed 16 nucleotide changes that resulted in four amino acid substitutions; T432D, G517D, G530S, and Q542R. The GO proteins from both ATCC 9029 and ACMO4 were heterologously expressed, purified, and compared biochemically. The two enzymes showed no difference in their apparent Km value for glucose (30 mM), but the Vmax of GO-ACMO4 (515.6 unit/mg) was 10% higher than that of GO-ATCC 9029, resulting in a 10% higher specific activity.

Alleles↗
PubMed2001

Caspase-3-mediated cleavage of the NF-kappa B subunit p65 at the NH2 terminus potentiates naphthoquinone analog-induced apoptosis.

The transcription factor nuclear factor kappaB (NF-kappaB) plays a crucial role in immune and inflammatory response, and protects cells from apoptosis. In this report, we investigate whether the NF-kappaB signaling pathway is blocked during apoptosis induced by 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (NA), an analog of naphthoquinone. It is observed that NA triggers apoptotic cell death in HeLa cells and destroys resistance to apoptosis caused by tumor necrosis factor-alpha. Data presented in this study establish that p65/RelA, a subunit of NF-kappaB, is cleaved at Asp(97) by caspase-3 during apoptosis. Caspase-3-cleaved p65 loses transcriptional activity and potentiates NA-induced apoptosis, in contrast to an uncleavable mutant of p65, which protects the cell from apoptosis. Caspase-3, which is responsible for the cleavage of p65, is activated via the cytochrome c/caspase-9 signaling pathway rather than Fas/caspase-8 pathway during NA-induced apoptosis. Our results suggest that NA induces apoptosis by the negative regulation of cell survival through caspase-3-mediated cleavage of p65.

Apoptosis↗
PubMed2001

Postmenopausal endogenous oestrogens and risk of endometrial cancer: results of a prospective study.

We assessed the association of postmenopausal serum levels of oestrogens and sex hormone-binding globulin (SHBG) with endometrial cancer risk in a case-control study nested within the NYU Women's Health Study cohort. Among 7054 women postmenopausal at enrolment, 57 cases of endometrial cancer were diagnosed a median of 5.5 years after blood donation. Each case was compared to 4 controls matched on age, menopausal status at enrolment, and serum storage duration. Endometrial cancer risk increased with higher levels of oestradiol (odds ratio = 2.4 in highest vs lowest tertile, P for trend = 0.02), percent free oestradiol (OR = 3.5, P< 0.001), and oestrone (OR = 3.9, P< 0.001). Risk decreased with higher levels of percent SHBG-bound oestradiol (OR = 0.43, P = 0.03) and SHBG (OR = 0.39, P = 0.01). Trends remained in the same directions after adjusting for height and body mass index. A positive association of body mass index with risk was substantially reduced after adjusting for oestrone level. Our results indicate that risk of endometrial cancer increases with increasing postmenopausal oestrogen levels but do not provide strong support for a role of body mass index independent of its effect on oestrogen levels.

Adult↗
PubMed2001

Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects.

Mutations in several genes encoding transcription factors of the hepatocyte nuclear factor (HNF) cascade are associated with maturity-onset diabetes of the young (MODY), a monogenic form of early-onset diabetes mellitus. The ability of the orphan nuclear receptor small heterodimer partner (SHP, NR0B2) to modulate the transcriptional activity of MODY1 protein, the nuclear receptor HNF-4alpha, suggested SHP as a candidate MODY gene. We screened 173 unrelated Japanese subjects with early-onset diabetes for mutations in this gene and found five different mutations (H53fsdel10, L98fsdel9insAC, R34X, A195S, and R213C) in 6 subjects as well as one apparent polymorphism (R216H), all present in the heterozygous state. Interestingly, all of the subjects with the mutations were mildly or moderately obese at onset of diabetes, and analysis of the lineages of these individuals indicated that the SHP mutations were associated with obesity rather than with diabetes. Therefore, an additional group of 101 unrelated nondiabetic subjects with early-onset obesity was screened for mutations in the SHP gene. Two of the previously observed mutations (R34X and A195S) and two additional mutations (R57W and G189E) were identified in 6 subjects, whereas no mutations were identified in 116 young nondiabetic lean controls (P = 0.0094). Functional studies of the mutant proteins show that the mutations result in the loss of SHP activity. These results suggest that genetic variation in the SHP gene contributes to increased body weight and reveal a pathway leading to this common metabolic disorder in Japanese.

Adolescent↗
PubMed2001

A novel plasmid-mediated beta-lactamase that hydrolyzes broad-spectrum cephalosporins in a clinical isolate of Klebsiella pneumoniae.

A new extended-spectrum beta-lactamase with an isoelectric point (pI) of 6.2 was detected in Klebsiella pneumoniae F161 that was isolated from a patient with infection. This strain was highly resistant to the third or fourth generation cephalosporins such as ceftazidime, ceftriaxone, cefoperazone, and cefpirome. Analysis of this strain by the double disk diffusion test showed synergies between amoxicillin-clavulanate (AMX-CA) and cefotaxime, and AMX-CA and aztreonam, which suggested that this strain produced a extended-spectrum beta-lactamase (ESBL). Genetic analysis revealed that the resistance was due to the presence of a 9.4-kb plasmid, designated as pKP161, encoding for new beta-lactamase gene (bla). Sequence analysis showed that a new bla gene of pKP161 differed from bla(TEM-1) by three mutations leading to the following amino acid substitutions: Val84 --> Ile, Ala184 --> Val, and Gly238 --> Ser. These mutations have not been reported previously in the TEM type beta-lactamases produced by clinical strains. The novel beta-lactamase was overexpressed in E. coli and purified by ion exchange chromatography on Q-Sepharose and CM-Sepharose, and then further purified by gel filtration on Sehadex G-200. The catalytic activity of the purified beta-lactamase was confirmed by the nitrocefin disk.

Amino Acid Sequence↗
PubMed2001

Clinical characteristics and prognosis of patients with hepatoblastoma.

Hepatoblastoma is a rare pediatric malignancy that frequently appears in an advanced unresectable stage. Improved resectability and survival rate have been reported with the help of neoadjuvant chemotherapy. Between January 1987 and June 1995 a series of 20 patients were managed with a diagnosis of hepatoblastoma. The median age at diagnosis was 13 months (2 months to 7 years 10 months) with a male/female ratio of 13:7. Chemotherapy effectively reduced the tumor volume (with statistical significance: p = 0.008) and was able to convert seven of nine initially unresectable tumors (78%) to resectable ones. Altogether, 14 operations were done, 12 radical and 2 palliative, with or without adjuvant chemotherapy. The whole population was followed for a median duration of 33 months; and the median survival for the whole group was 26 months. The curative resection group displayed a 5-year survival rate of 61.1%, but none in the noncurative group survived more than 13 months (p = 0.0001). In the univariate analysis for prognostic factors, large tumor size at diagnosis and the absence of thrombocytopenia were associated with poor survival, but these differences were not statistically significant. Pure fetal histology was not associated with better prognosis. In this new era of neoadjuvant chemotherapy, the optimal management strategy for hepatoblastoma is still debated, with radical surgical resection at the earliest possible time being the final goal. For now an individualized approach appears to be the protocol of choice.

Chemotherapy, Adjuvant↗
PubMed2001

Benchmarking the endodontic literature on MEDLINE.

The purpose of this study was to identify and quantify the endodontic literature available for clinical decision making. A search strategy based on Medical Subject Headings for endodontics was developed to examine MEDLINE. The identified articles were limited to human subjects and English. Sensitive and specific methodological search filters identified four categories of information: etiology, diagnosis, therapy, and prognosis. The results were then subdivided by year to identify trends. Between 1990 and 1998 MEDLINE identified 3,152 articles published in English on endodontics in humans. The number of articles per year (mean +/- SD) for sensitive and specific searches was etiology (28+/-10, 1+/-2), diagnosis (38+/-11, 1+/-1), therapy (59+/-15, 3+/-3), and prognosis (40+/-13, 10+/-5), respectively. The number of articles in each category increased by 1 to 3% each year. There were 150 articles/yr in endodontics in at least 120 journals cited on MEDLINE on which to base clinical decisions.

Analysis of Variance↗
PubMed2001

Chronic hepatitis: in vivo proton MR spectroscopic evaluation of the liver and correlation with histopathologic findings.

PURPOSE: To correlate the in vivo hydrogen 1 ((1)H) magnetic resonance (MR) spectroscopic features of the chronic hepatitis-involved liver with the histopathologic stages of fibrosis. MATERIALS AND METHODS: Seventy-five patients with chronic hepatitis were examined with (1)H MR spectroscopy, which was performed in the right hepatic lobe. The peak areas of glutamine and glutamate complex (Glx), phosphomonoesters (PME), glycogen and glucose complex (Glyu), and lipid were measured on the liver spectra. The histopathologic features were correlated with the in vivo (1)H MR spectroscopic findings at each stage of chronic hepatitis. Fifteen healthy volunteers also were included as a control group. RESULTS: (1)H MR spectroscopy depicted Glx, PME, Glyu, and lipid in all livers. In the normal livers, the calculated mean (+/- SD) relative metabolite-to-lipid ratios of Glx, PME, and Glyu were 0.14 +/- 0.04, 0.03 +/- 0.01, and 0.21 +/- 0.04, respectively. The mean value of each metabolite-to-lipid ratio was significantly different between all stages of chronic hepatitis, and with the exception of the mean ratio at the interval between stages 0 and 1 (P > .05), the mean value increased significantly with increasing stage (P < .05). A pronounced peak was demonstrated at 3.9-4.1 ppm at (1)H MR spectroscopy of all stages of chronic hepatitis except stage 0. CONCLUSION: The increased Glx, PME, and Glyu levels relative to the lipid content with chronic hepatitis indicated the severity of fibrosis and thus were concordant with the histopathologic stages. In vivo (1)H MR spectroscopy might be a substitute for liver biopsy in the diagnosis and staging of chronic hepatitis.

Adolescent↗
PubMed2001

A case of localized persistent interstitial pulmonary emphysema.

Interstitial pulmonary emphysema is a well-documented complication of assisted mechanical ventilation in premature infants with respiratory distress syndrome. Localized persistent interstitial pulmonary emphysema (LPIPE) confined to a single lobe was incidentally presented in a 4-day-old female infant. This patient was a normal full-term baby with no respiratory distress symptom and no experience of assisted mechanical ventilation. Chest radiograph showed radiolucent area in right lower lobe zone, which needed differential diagnosis from other congenital lesions such as congenital cystic adenomatoid malformation and congenital lobar emphysema. CT scan showed irregular-shaped air cystic spaces and pathologically, cystic walls primarily consisted of compressed lung parenchyma and loose connective tissue intermittently lined by multinucleated foreign body giant cells.

Diagnosis, Differential↗
PubMed2001

Frequencies of fetal chromosomal abnormalities at prenatal diagnosis: 10 years experiences in a single institution.

We present frequencies of fetal chromosomal abnormalities in 4,907 prenatal cytogenetic examinations at Samsung Cheil Hospital from 1988 to 1997 for 10 yr duration. Prenatal karyotypes were undertaken in 3,913 amniotic fluid samples, 800 chorionic villi samples, and 194 percutaneous umbilical blood samples. The frequency of fetal abnormal karyotypes was 3.1% (150 cases). Numerical chromosome abnormalities were 87 cases (1.8%) and structural aberrations of chromosomes were 63 cases (1.3%). In the numerical chromosomal abnormalities, the frequency of trisomy 21 was by far the highest (36 cases), followed by trisomy 18 in 22 cases and sex chromosome aneuploidies in 19 cases. In the structural chromosomal aberrations, 5 cases had the inversions in chromosome 2, 7, 17, and Y. Chromosomal deletions in 6 cases and additions in 4 cases were analysed. Of the remaining 47 translocation in abnormal fetuses, reciprocal translocation was in 26 cases and Robertsonian translocation in 21 cases. Among them, 41 cases were balanced translocation and 6 were unbalanced. Thirty five cases of translocation were inherited from one of the parents. Four had de novo chromosome rearrangements, and 8 cases were unknown.

Chromosome Aberrations↗
PubMed2001

Retinal vein occlusion in two patients with primary antiphospholipid syndrome.

Primary antiphospholipid syndrome (APS) is a disease producing vascular thrombus with antiphospholipid antibody without association with autoimmune diseases as systemic lupus erythematosus. Retinal vein occlusion is a rare vascular manifestation in primary APS. We describe 2 cases of primary APS presenting with developing blurred vision. Each had central retinal vein occlusion and high titer of IgG anticardiolipin antibody.

Adult↗
PubMed2001

Mechanism-based inhibition of human cytochrome P450 1A1 by rhapontigenin.

Recently we reported that resveratrol (trans-3,4',5-trihydroxystilbene) showed selective inhibition of recombinant human cytochrome P450 (P450) 1A1 in a concentration-dependent manner. The inhibition of recombinant human P450 1A1, 1A2, or 1B1 by various hydroxystilbene compounds having a similar structure to resveratrol was investigated using bacterial membranes from a human P450/NADPH-P450 reductase bicistronic expression system to find new candidates for cancer chemopreventive agents. Of seven compounds tested, rhapontigenin (3,3',5-trihydroxy-4'-methoxystilbene) exhibited a potent and selective inhibition of human P450 1A1 with an IC50 value of 0.4 microM. Rhapontigenin showed 400-fold selectivity for P450 1A1 over P450 1A2 and 23-fold selectivity for P450 1A1 over P450 1B1. Rhapontigenin did not show any significant inhibition of ethoxyresorufin O-deethylation (EROD) activity in human liver microsomes, the other human P450s such as P450 2E1, P450 3A4, P450 2D6, P450 2C8, and P450 2C9, or human NADPH-P450 reductase. We have further investigated the inhibition kinetics of P450 1A1 by rhapontigenin. Rhapontigenin inhibited EROD activity of expressed human P450 1A1 in a competitive manner. The loss of EROD activity was time- and concentration-dependent. The values for K(i) and k(inactivation) were 0.09 microM and 0.06 min(-1), respectively. The loss was not blocked by the trapping agents glutathione, N-acetylcysteine, or dithiothreitol. These results suggest that rhapontigenin is a potent mechanism-based inactivator of human P450 1A1 and may be considered as a good candidate for a cancer chemopreventive agent in humans.

Cytochrome P-450 CYP1A1↗
PubMed2001

Transverse sacral fractures: case series and literature review.

OBJECTIVES: To report experience with transverse sacral fracture, an uncommon injury frequently associated with neurologic deficit, and to perform a meta-analysis of the literature in order to define the role of decompression for the management of sacral fractures. DESIGN: A review of 7 cases. SETTING: A university-affiliated tertiary care centre. PATIENTS: Seven patients with transverse fractures of the sacrum. The mean follow-up was 13 months. INTERVENTIONS: A review of the clinical data and a search of the literature for studies that reported on 4 or more patients with a transverse sacral fracture. MAIN OUTCOME MEASURES: Mechanism of injury, type of neurologic deficit and its management. RESULTS: The most common mechanism in the 7 study patients was a fall from a height. Six patients had neurologic deficits, mostly in the form of bowel or bladder disturbance. Five of these were treated with surgical decompression, and 4 of them had an improvement in neurologic function. The 7 original studies from the literature dealt with a total of 55 patients. As in the study patients, falls from a height and motor vehicle accidents predominated as the mechanisms of injury. In contrast to patients in this study, 20 of 48 patients in the literature review with neurologic deficits were treated conservatively. CONCLUSIONS: The outcomes in this study are similar to those reported in the literature. The place of surgical decompression for patients with neurologic deficit cannot be clearly determined from the evidence currently available.

Accidental Falls↗
PubMed2001

Oviductural carcinoma in B6C3F1 female mice exosed to 0.5 ppm ozone.

The toxicity and carcinogenecity of ozone was evaluated in B6C3F1 mice exposed to 0.5 ppm ozone via inhalation for 12 w, during which no ozone-related deaths occurred. Decreases in mean body weights of both genders exposed to ozone were sporadically seen, and mean absolute and relative weights of several organs from male and female groups receiving ozone were lower than those of respective air-control groups. No ozone-related increased neoplasm incidences were observed in most organs, including the lung; however, oviductural carcinomas were seen in the ozone-exposed females. Although ozone does not induce lung cancer under our experimental condition, it induces oviductural carcinomas in B6C3F1 mice.

Animals↗
PubMed2001

Design and synthesis of fluoroquinophenoxazines that interact with human telomeric G-quadruplexes and their biological effects.

In this study we have identified a new structural motif for a ligand with G-quadruplex interaction that results in biological effects associated with G-quadruplex-interactive compounds. Fluoroquinolones have been reported to possess weak telomerase inhibitory activity in addition to their better known bacterial gyrase poisoning. Starting with a fluoroquinobenzoxazine, which has modest potency in a human topoisomerase II assay, we have designed a more potent inhibitor of telomerase that has lost its topoisomerase II poisoning activity. This fluoroquinophenoxazine (FQP) interacts with G-quadruplex structures to inhibit the progression of Taq polymerase in a G-quadruplex polymerase stop assay. In addition, we demonstrate by 1H NMR studies that this compound interacts with telomeric G-quadruplex structures by external stacking to the G-tetrad with both the unimolecular fold-over and the parallel G-quadruplex structures. A photocleavage assay confirms the FQP interaction site, which is located off center of the external tetrad but within the loop region. Molecular modeling using simulated annealing was performed on the FQP-parallel G-quadruplex complex to determine the optimum FQP orientation and key molecular interactions with the telomeric G-quadruplex structure. On the basis of the results of these studies, two additional FQP analogues were synthesized, which were designed to test the importance of these key interactions. These analogues were evaluated in the Taq polymerase stop assay for G-quadruplex interaction. The data from this study and the biological evaluation of these three FQPs, using cytotoxicity and a sea urchin embryo system, were in accord with the predicted more potent telomeric G-quadruplex interactions of the initial lead compound and one of the analogues. On the basis of these structural and biological studies, the design of more potent and selective telomeric G-quadruplex-interactive compounds can be envisaged.

Animals↗