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Biomedical subjects

S H Hong

Publications and source records attributed to S H Hong.

At least 127 records · Page 7Linked to original sources

MR of hippocampal sclerosis: comparison of qualitative and quantitative assessments.

PURPOSE: Our goal was to compare the diagnostic accuracy of subjective visual assessment versus MR volumetry in evaluating hippocampal sclerosis and to determine whether MR volumetry is needed in the lateralization of this disease process. METHODS: MR imaging findings were studied retrospectively in 48 patients who underwent surgery for temporal lobe epilepsy and were compared with findings at MR volumetry on an Allegro workstation. Both visual assessment and volumetry were carried out in a blinded fashion with oblique coronal T1-weighted three-dimensional MP-RAGE images obtained on either 1.0-T or 1.5-T units. Normal right-left volumetric differences were recorded in 30 control subjects. The optimum cutoff threshold value for right-left volumetric differences in the sensitivity and specificity of volumetric measurement was obtained from receiver operating characteristic analysis. RESULTS: Sensitivity, specificity, positive and negative predictive values, and accuracy of visual assessment were 86%, 83%, 86%, 83%, and 85%, respectively. For MR volumetry, with the optimum cutoff threshold value of right-left difference at 0.3 cm3, sensitivity, specificity, positive and negative predictive values, and accuracy were 81%, 82%, 87%, 83%, and 85%, respectively. CONCLUSION: Visual assessment was slightly superior to or similar to MR volumetry in assessing unilateral hippocampal sclerosis. MR volumetry of the hippocampus may not be needed for the evaluation of most cases of suspected hippocampal sclerosis.

Adolescent↗

Ankle arthrography and chronic lateral ankle instability.

Sixty-five ankle arthrograms of the patients who underwent surgical reconstruction for their chronic ankle instability from 1987 to 1995 were studied retrospectively by comparing their operative findings. There were 15 cases (23.1%) with definite positive arthrographic findings. In the remaining 50 cases (76.9%), the arthrograms showed a "tear-drop" extravasation of dye beneath the fibular tip which we called "suspectable positive". Of these all but one, which had normal ligament, proved to correspond to the operative finding. As there was only one false positive finding among our surgical cases with both the "definite" and "suspectable" positive arthrograms, we concluded that ankle arthrography is relatively reliable and may be worth doing even in chronic cases if only for reference. Even when other diagnostic methods are negative, arthrography might help surgeons make surgical decisions in clinical symptomatic cases.

Adolescent↗

Genetic variation of the apolipoprotein B gene in Korean patients with coronary artery disease.

In view of the clinical importance of apolipoprotein B (apo B) as a major risk factor for coronary artery disease (CAD), we investigated the two polymorphisms (signal peptide and XbaI) of the apo B gene in 235 Korean patients with CAD and in 216 normal controls. The insertion allele (INS) frequency of signal peptide polymorphism was significantly higher in cases than the controls (P<0.05). Signal peptide polymorphism was also associated with levels of plasma cholesterol, triglyceride and low density lipoprotein-cholesterol. However, XbaI polymorphism was not associated with plasma lipid levels. Therefore, our results suggest that signal peptide polymorphism of the apo B gene might be one of the factors in explaining an association in Korean CAD patients.

Adult↗

SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia.

Retinoic acid receptors (RARs) are hormone-regulated transcription factors that control key aspects of normal differentiation. Aberrant RAR activity may be a causal factor in neoplasia. Human acute promyelocytic leukemia, for example, is tightly linked to chromosomal translocations that fuse novel amino acid sequences (denoted PML, PLZF, and NPM) to the DNA-binding and hormone-binding domains of RARalpha. The resulting chimeric receptors have unique transcriptional properties that may contribute to leukemogenesis. Normal RARs repress gene transcription by associating with ancillary factors denoted corepressors (also referred to as SMRT, N-CoR, TRAC, or RIP13). We report here that the PML-RARalpha and PLZF-RARalpha oncoproteins retain the ability of RARalpha to associate with corepressors, and that this corepressor association correlates with certain aspects of the leukemic phenotype. Unexpectedly, the PLZF moiety itself can interact with SMRT corepressor. This interaction with corepressor is mediated, in part, by a POZ motif within PLZF. Given the presence of POZ motifs in a number of known transcriptional repressors, similar interactions with SMRT may play a role in transcriptional silencing by a variety of both receptor and nonreceptor transcription factors.

DNA-Binding Proteins↗

Type II protein kinase A up-regulation is sufficient to induce growth inhibition in SK-N-SH human neuroblastoma cells.

We have previously reported that overexpression of RII beta subunit of protein kinase A, which markedly reduces RI alpha protein, induces growth inhibition in SK-N-SH human neuroblastoma cells. To determine whether the reduction of RI alpha or protein kinase A isozyme type I is essential in the growth inhibition of SK-N-SH cells, we overexpressed RI alpha in sense and antisense orientation. Type I protein kinase A activity was increased in the RI alpha-overexpressing cells and was decreased in the RI alpha antisense-expressing cells. However, the changes in type I protein kinase A activities did not affect cell growth. Overexpression of RII beta or C alpha increased type II protein kinase A and inhibited cell growth in both cell lines regardless of the type I protein kinase A level. These results indicate that type II protein kinase A is the main effector in the cAMP-mediated growth regulation of SK-N-SH human neuroblastoma cells.

Affinity Labels↗

Identification and expression of uvi31+, a UV-inducible gene from Schizosaccharomyces pombe.

The Schizosaccharomyces pombe uvi31+ gene has been previously isolated as a UV-inducible gene [Lee JK et al. (1994) Biochem Biophys Res Commun 202:1113-1119]. This gene encodes a protein of about 12 kDa with 57% amino acid sequence similarity to Escherichia coli BolA protein which is known to be involved in switching between the cell elongation and septation systems during the cell division cycle. The putative Mlul cell cycle box (MCB), SWI4/6-dependent cell cycle box (SCB), and gear-box elements are found in the upstream region of uvi31+ gene, suggesting that this gene shows the cell cycle-regulated and growth phase-dependent expression. Interestingly, the level of uvi31+ transcript varies throughout the cell cycle, peaking in G1 phase before septation, and also shows the growth phase-dependent pattern during cellular growth, increasing maximally at the diauxic shift phase just before stationary phase. Furthermore, the transcript level of this gene is raised after S phase arrest, and is also increased maximally at 4 hr after UV irradiation of 240 J/m2. These results suggest that the delayed induction of uvi31+ gene after UV irradiation may be caused by cell cycle control of this gene after DNA replication checkpoint arrest. Thus, the uvi31+ gene may play a role in controlling the progress of the cell cycle after DNA damage (UV irradiation).

Amino Acid Sequence↗

Proliferating cell nuclear antigen expression and its relationship to malignancy potential in invasive colorectal carcinomas.

PURPOSE: Cellular proliferative activity is a useful indicator of biologic aggressiveness in colorectal carcinoma. Immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) has important advantages of maintaining tissue architecture and technical simplicity. The aim of this study was to investigate the correlation between proliferative activity and malignancy potential in colorectal carcinomas to determine whether proliferative index of cancer cells has prognostic significance using immunohistochemical technique. METHODS: Proliferation index at the invasive tumor margin of 86 paraffin sections of advanced colorectal carcinomas was assessed by immunohistochemical study using a mouse monoclonal antibody to PCNA (PC-10) and was compared with conventional clinicopathologic factors and other possible prognostic parameters, including p53 overexpression, tissue carcinoembryonic antigen immunoreactivity pattern, and flow cytometric DNA ploidy. In addition, recurrence and survival were analyzed in accordance with degree of PCNA expression. RESULTS: PCNA labeling index (PCNA-LI) increased significantly as the Astler-Coller stage advanced (P = 0.0001). Strong correlations were observed between PCNA-LI and various pathologic parameters, including histologic differentiation (P = 0.0027), lymphatic invasion (P = 0.0001), vascular invasion (P = 0.0001), lymph node metastasis (P = 0.0001), and liver metastasis (P = 0.0036). Mean PCNA-LI was also significantly higher in tumors with DNA aneuploidy (P = 0.0006) and negative and cytoplasmic patterns of carcinoembryonic antigen immunoreactivity (P = 0.01). Linear relationships were demonstrated between PCNA-LI and clinical outcomes; recurrence rate was significantly greater in the group with higher than the mean PCNA-LI, who underwent curative resection (P < 0.01), and four-year survival rates for both overall and curative cases with higher than the mean PCNA-LI were significantly poorer than those with lower than mean PCNA-LI (P < 0.005 and P < 0.01, respectively). CONCLUSION: Evaluation of PCNA-LI at the invasive tumor margin in colorectal carcinomas is suggested to be valuable in predicting those people with a higher potential for metastasis and recurrence after surgery; thus, the evaluation is helpful in planning reasonable adjuvant therapy, even in the earlier stages.

Cell Division↗

Iatrogenic secondary infertility caused by residual intrauterine fetal bone after midtrimester abortion.

Eleven women with secondary infertility had ultrasonographic findings of intrauterine calcification. Infertility developed in all women after operative termination of midtrimester pregnancy. Dilation and curettage or hysteroscopic removal confirmed residual fetal bony fragments. The removal of these bony fragments was associated with therapeutic success for infertility.

Abortion, Induced↗

Genetic variations of the apo E-CI-CII cluster gene in Koreans.

OBJECTIVES: To investigate the allele frequencies of the apolipoprotein (apo) E-CI-CII cluster gene in Koreans, and its relation to plasma lipid and lipoprotein levels. METHODS: The study subjects consisted of healthy Korean individuals (apo E, 145; apo CI and CII, 81) who were randomly selected via health screening. For polymorphism analysis, DNA was amplified by polymerase chain reaction (PCR). The one-way analysis of variance (ANOVA) test was performed to compare the mean of lipid levels among different genotypes. RESULTS: The apo E polymorphism in the Korean population appeared as the E4/2, E3/2, E3/3, E4/3, and E4/4 genotypes. The epsilon 3 allele was the most frequent, as in other populations. The apo E polymorphism showed the lack of association with plasma lipid levels in this population. On the other hand, we demonstrated AvaII polymorphism of the apo CII gene by PCR technique. Cholesterol and triglyceride levels were varied significantly among the AvaII genotypes (p < 0.05). CONCLUSION: No effect of the apo E allele on lipid levels was seen in the Korean population. This result suggests that it might be one of the factors in explaining the low prevalence rate of atherosclerosis in the Korean population. Also, the AvaII polymorphism analysis by PCR is a simple and less time-consuming method.

Apolipoprotein C-I↗

Genetic variation of the angiotensin-converting enzyme gene: increased frequency of the insertion allele in Koreans.

In view of the clinical importance of angiotensin-converting enzyme (ACE) as a major marker for cardiovascular diseases, we investigated insertion/deletion (I/D) polymorphism of the ACE gene in Koreans. Genotype frequencies were examined by polymerase chain reaction in 171 patients with coronary artery disease (CAD) and 120 healthy subjects. Allele frequencies of ACE polymorphism in Koreans were not significantly different between patient and control groups. In addition, association between ACE genotypes and the number of stenosed coronary arteries was not detected. ACE genotypes in the CAD group were not associated with body mass index and plasma lipid levels. Thus, our results suggest that, at least in Koreans, I/D polymorphism of the gene is unlikely to be a useful marker for CAD subjects. However, the I allele frequency of Koreans (0.58) was higher than that of Caucasian populations (0.47) but lower than that of Samoan (0.91) and Yanomami (0.85) populations. Here, we discuss the clinical and ethnic importance of ACE polymorphism.

Aged↗

A conformational switch in nuclear hormone receptors is involved in coupling hormone binding to corepressor release.

Nuclear hormone receptors are ligand-regulated transcription factors that modulate gene expression in response to small, hydrophobic hormones, such as retinoic acid and thyroid hormone. The thyroid hormone and retinoic acid receptors typically repress transcription in the absence of hormone and activate it in the presence of hormone. Transcriptional repression is mediated, in part, through the ability of these receptors to physically associate with ancillary polypeptides called corepressors. We wished to understand the mechanism by which corepressors are recruited to unliganded nuclear hormone receptors and are released on the binding of hormone. We report here that an alpha-helical domain located at the thyroid hormone receptor C terminus appears to undergo a hormone-induced conformational change required for release of corepressor and that amino acid substitutions that abrogate this conformational change can impair or prevent corepressor release. In contrast, retinoid X receptors appear neither to undergo an equivalent conformational alteration in their C termini nor to release corepressor in response to cognate hormone, consistent with the distinct transcriptional regulatory properties displayed by this class of receptors.

Amino Acid Sequence↗

Immunocytochemical analysis of peptide hormone processing: importance of the positively charged N-terminal domain of signal peptide in correct ER targeting in yeast cells.

We used a morphological approach to determine the topogenic role of the signal peptide in mediating the ER translocation of yeast prepro-alpha-factor. In prepro-alpha-factor-somatostatin hybrids, changes in the N-terminal amino acid sequence from wild-type NH2-Met-Arg-Phe (MRF) to NH2-Met-Phe-Lys (MFK) caused a subtle difference in protein trafficking in yeast cells. Immunofluorescence microscopy on semithin cryosections and immunoelectron microscopy on ultrathin sections showed that the transposition of the charged amino acid at N-terminus caused the precursors to be associated with either nucleus or mitochondria. This suggests that the secretory proteins are mistargeted to the irrelevant organelles as the result of inefficient ER translocation. Structural aspects of nuclear or mitochondrial targeting proteins and common principles in membrane translocation systems account for the mistargeting of overexpressed mutant hybrid precursors that are not rapidly translocated into the ER. Based on our immunocytochemical study on individual cells, we propose here that the positively charged N-terminal domain of signal peptide is important not merely in the efficiency of ER translocation, but also in appropriate targeting of peptide hormone precursors in yeast cells where post-translational ER translocation is known to occur frequently.

Biological Transport↗

Association between genetic variations of apo AI-CIII-AIV cluster gene and hypertriglyceridemic subjects.

Several studies have suggested that genetic variations of the apolipoprotein (apo) AI-CIII-AIV cluster gene are associated with hyperlipidemia or atherosclerosis. These investigations were carried out mainly with Caucasian groups; there have been few associated studies involving non-Caucasian groups. This study was conducted to elucidate the association between five restriction fragment length polymorphisms (RFLPs) of the apo AI-CIII-AIV cluster gene and Korean hypertriglyceridemic subjects. The rare allele frequencies of the XmnI and SstI polymorphic sites in the patients were significantly higher than those of the control group (P <0.05). These two polymorphic sites had relation to linkage disequilibrium in the hypertriglyceridemic subjects (delta = -0.2733). In addition, S2 allele frequency of the SstI RFLP in Koreans was more frequent than that of Caucasians reported previously. The rare allele of XmnI and SstI polymorphic sites was associated with increased triglyceride concentrations in the hypertriglyceridemic group (P <0.005). Koreans have a much lower prevalence of hyperlipidemia than Caucasians. Nevertheless, this study showed a similar trend with results from Caucasian groups, thereby confirming that genetic variations of the apo AI-CIII-AIV cluster gene are likely to be significant markers for hypertriglyceridemic subjects. Thus, RFLP loci of the apo AI-CIII-AIV cluster gene may be a useful genetic marker for clinical or population studies.

Adult↗

Complementation of a yeast top2ts mutation by a cDNA encoding rat DNA topoisomerase II alpha.

A series of yeast expression plasmids which comprise segments of the cDNA sequences encoding rat topo II alpha have been constructed. The transcription of these constructs is under the control of the yeast GAL1 promoter. Galactose-dependent expression of the cloned rat topo II alpha cDNA complemented a yeast top2ts mutation, as well as a deletion mutation at the yeast TOP2 locus. Truncation of 12 N-terminal amino acids and/or 158 C-terminal amino acids of rat topo II alpha had no effect on its ability functionally to substitute for top2ts. Moreover, a cDNA construct with mutated putative leucine zipper domain (amino acids 993-1013) retained the complementation activity. These observations suggest that transformants capable of conditional topo II alpha expression can be exploited as a useful model system for studies on the structure-function relationships of wild-type and mutated topo II alpha, as well as the interplay of potential antitumor drugs with the enzyme.

Animals↗

Psychosocial and demographic predictors of pediatric psychotropic medication use.

The effects of age, gender, and family background on children's use of prescription psychoactive medications were studied. Patient and prescribing information was obtained for children enrolled as dependents in any of five prescription drug benefit plans during the period from December 29, 1992, through December 28, 1993. A binary response model was specified under the assumption of logistic distribution of probabilities of psychotropic drug use. The independent variables were family size, parenting type (single- or two-parent family), parental use of psychotropic medications, and child's age, gender, and the interaction between age and gender. Logistic regression analysis was conducted not only for overall psychotropic drug use but also for antidepressants, antianxiety drugs, and CNS stimulants. The sample included 3144 children; 3.9% received psychotropic drugs. Family size and parenting type had no effect on overall use of psychotropic drugs by children, but children were more likely to receive psychotropic drugs if the parents took them. The study showed an interaction between age and gender. At younger ages, boys were more likely than girls to receive psychotropic drugs; the opposite was true at older ages. For particular subcategories of drugs the study showed that (1) boys were more likely than girls, and young children were more likely than older children, to receive CNS stimulants, (2) children from single-parent families were less likely to use antidepressants than children from two-parent households, and (3) the influence of mothers' psychotropic drug use extended to all three drug classes, but the influence of fathers' psychotropic drug use existed for antidepressants only. The effects of demographic and familial factors on children's use of psychotropic drugs varied according to the drug class.

Adolescent↗

Identification of the DNA damage-responsive elements of the rhp51+ gene, a recA and RAD51 homolog from the fission yeast Schizosaccharomyces pombe.

The Schizosaccharomyces pombe rhp51+ gene encodes a recombinational repair protein that shares significant sequence identities with the bacterial RecA and the Saccharomyces cerevisiae RAD51 protein. Levels of rhp51+ mRNA increase following several types of DNA damage or inhibition of DNA synthesis. An rhp51::ura4 fusion gene was used to identify the cis-acting promoter elements involved in regulating rhp51+ expression in response to DNA damage. Two elements, designated DRE1 and DRE2 (for damage-responsive element), match a decamer consensus URS (upstream repressing sequence) found in the promoters of many other DNA repair and metabolism genes from S. cerevisiae. However, our results show that DRE1 and DRE2 each function as a UAS (upstream activating sequence) rather than a URS and are also required for DNA-damage inducibility of the gene. A 20-bp fragment located downstream of both DRE1 and DRE2 is responsible for URS function. The DRE1 and DRE2 elements cross-competed for binding to two proteins of 45 and 59 kDa. DNase I footprint analysis suggests that DRE1 and DRE2 bind to the same DNA-binding proteins. These results suggest that the DRE-binding proteins may play an important role in the DNA-damage inducibility of rhp51+ expression.

Base Sequence↗

Differential expression of the rhp51+ gene, a recA and RAD51 homolog from the fission yeast Schizosaccharomyces pombe.

The rhp51+ gene encodes three transcripts of 1.9, 1.6 and 1.3 kb which have at least six polyadenylation sites. Primer-extension analysis revealed that two transcription start points (tsp) at - 166 and - 136 were responsible for the DNA damage inducibility of this gene. Northern blot analyses showed that the three transcripts were expressed differentially in response to a variety of DNA damage. During the mitotic cell cycle, only the largest transcript exhibited periodic expression, reaching the maximal level in front of the cdc22+ transcript which peaks at the G1/S boundary. Unexpectedly, the steady-state levels of the three transcripts were differentially regulated during the growth cycle. The largest and smallest transcripts accumulated in large quantity at the diauxic shift and during the entry into stationary phase, respectively. To localize the regions responsible for the differential expression of rhp51+, we constructed rhp51::ura4 and ura4::rhp51 hybrid genes, and analyzed their expression patterns in response to methyl methanesulfonate (MMS)-induced DNA damage. The results showed that the promoter region and 5' half of rhp51+ are sufficient to confer damage-responsiveness while the 3' end of the gene alone can direct the formation of multiple, discrete 3' ends of the transcripts. From these results, we conclude that this novel one gene-multiple product system is possible through the cooperation of both the promoter and 3' terminal regions.

Amino Acid Sequence↗