Biomedical subjects

Myung-Sun Kim

Publications and source records attributed to Myung-Sun Kim.

At least 19 recordsLinked to original sources

PubMed2007

Electrophysiological correlates of behavioral response inhibition in patients with obsessive-compulsive disorder.

In this study, we have attempted to determine the electrophysiological correlates of behavioral response inhibition in patients with obsessive-compulsive disorder (OCD). To evaluate response inhibition ability, we have used the Go/NoGo task and measured N2 and P3 event-related potential (ERP) components. Both the OCD and control groups exhibited greater and more frontally distributed N2 and P3 amplitudes in the NoGo condition compared to what we observed in the Go condition. However, the patients with OCD also manifested reduced NoGo-N2 and Go-N2 amplitudes at the frontocentral electrode sites compared to the controls. In addition, the NoGo-N2 amplitudes were more posteriorly distributed in patients with OCD than in controls. The NoGo-N2 amplitudes and latencies measured at the central sites were also negatively correlated with the obsession score on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The OCD and control groups were comparable with regard to Go-P3 and NoGo-P3 amplitude and latencies. Our findings suggest dysfunctions in frontal regions mediating response inhibition in OCD, consistent with the involvement of response inhibition in the pathophysiology of this disorder. In addition, NoGo-N2 seems to result in more accurate response inhibition measurements in patients with OCD than does NoGo-P3.

Adult↗

PubMed2007

Neuropsychological profiles of patients with obsessive-compulsive disorder: early onset versus late onset.

In this study, we assess the neuropsychological profiles of both early and late symptom-onset obsessive-compulsive disorder (OCD) patients. The early and late-onset OCD patients are compared to the control group with a series of neuropsychological measurements. The late-onset OCD patients exhibited impaired performance on the immediate and the delayed recall conditions of the Rey-Osterrieth Complex Figure Test (RCFT) and the letter and category fluency of the Controlled Oral Word Association Test (COWA), compared to the normal controls and the early-onset OCD patients. The controls and early-onset OCD patients did not differ on any of the neuropsychological measurements taken in this study. These results suggest that different neurophysiological mechanisms are in play in early and late-onset OCD patients, and age of onset can serve as a potential marker for the subtyping of OCD.

Adult↗

PubMed2006

Hyaluronan- and RNA-binding deubiquitinating enzymes of USP17 family members associated with cell viability.

BACKGROUND: Protein degradation by the ubiquitin system plays a crucial role in numerous cellular signaling pathways. Deubiquitination, a reversal of ubiquitination, has been recognized as an important regulatory step in the ubiquitin-dependent degradation pathway. RESULTS: While identifying putative ubiquitin specific protease (USP) enzymes that contain a conserved Asp (I) domain in humans, 4 USP17 subfamily members, highly homologous to DUB-3, have been found (USP17K, USP17L, USP17M, and USP17N), from human chorionic villi. Expression analysis showed that USP17 transcripts are highly expressed in the heart, liver, and pancreas and are expressed moderately in various human cancerous cell lines. Amino acid sequence analysis revealed that they contain the highly conserved Cys, His, and Asp domains which are responsible for the deubiquitinating activity. Biochemical enzyme assays indicated that they have deubiquitinating activity. Interestingly, the sequence analysis showed that these proteins, with exception of USP17N, contain the putative hyaluronan/RNA binding motifs, and cetylpyridinium chloride (CPC)-precipitation analysis confirmed the association between these proteins and intracellular hyaluronan and RNA. CONCLUSION: Here, we report that the overexpression of these proteins, with exception of USP17N, leads to apoptosis, suggesting that the hyaluronan and RNA binding motifs in these enzymes play an important role in regulating signal transduction involved in cell death.

Amino Acid Sequence↗

PubMed2006

Equivalent current dipole of word repetition effects in patients with obsessive-compulsive disorder.

We investigated cortical source localization of word repetition effects in patients with obsessive-compulsive disorder (OCD) by employing the equivalent current dipole (ECD) model with high-density 128 channels EEG and individual MRI as a realistic head model. Twelve OCD patients and 13 healthy control subjects performed a word/nonword discrimination task, in which the words and nonwords were visually presented, and some of the words appeared twice with a lag of one or five items. During the 200-500 ms post-stimulus period, the control group showed more positivity in the ERPs elicited by old words than in those elicited by new words, whereas the OCD patients did not. Furthermore, the OCD patients showed prolonged response times to the old words, as compared to the controls. We calculated the location and the power of the ECD sources at approximately 400 ms post-stimulus with the peak mean global field potentials. In both groups, the sources of word repetition effects were determined to be located in the inferior frontal gyrus. The right ECD powers of the ERP generators elicited by the new words were significantly higher in the OCD patients than in the control subjects. The OCD patients also exhibited significant alterations in the hemispheric asymmetry of ECD power during the processing of new words. These results suggest that OCD patients suffer from the encoding deficits in word processing, particularly in the left hemisphere.

Adult↗

PubMed2006

Proteomic analysis of recurrent spontaneous abortion: Identification of an inadequately expressed set of proteins in human follicular fluid.

Recurrent spontaneous abortion (RSA), defined as the loss of three or more consecutive pregnancies prior to the 20th week of gestation, affects up to 5% of the child-bearing population. To investigate the proteins associated with RSA, the protein expression in human follicular fluid was analyzed using 2-DE. Follicular fluid contains a variety of biologically important proteins for oocyte fertilization and follicle maturation in the mammalian reproductive process. Therefore, it can be used as a provisional source for identifying proteins involved in RSA. In this study, we identified five aberrantly expressed proteins (complement component C3c chain E, fibrinogen gamma, antithrombin, angiotensinogen, and hemopexin precursor) in follicular fluid from RSA patients with MALDI-TOF-MS and nano-LC MS/MS. Western blot analysis confirmed that the protein expression level of fibrinogen gamma and antithrombin was less in follicular fluid from RSA patients than those from normal controls. Semiquantitative RT-PCR and real-time PCR analyses revealed that mRNA level of these coagulation factors was also decreased significantly in chorionic villi of RSA patients compared with normal samples. Taken all together, it is likely that coagulation factors (fibrinogen gamma and antithrombin) play an important role in maintaining the normal pregnancy.

Abortion, Habitual↗

PubMed2006

Neuropsychological correlates of error negativity and positivity in schizophrenia patients.

The purpose of the present paper was to determine error-monitoring ability and its relationship with executive function in patients with schizophrenia. In order to evaluate error-monitoring ability, the error negativity (Ne) and error positivity (Pe) were measured using the Stroop task. The correct-related negativity (CRN) and positivity (Pc) were also measured. In addition, neuropsychological tests were administered in order to evaluate executive function. The patients with schizophrenia had significantly reduced Ne and augmented CRN amplitudes, but the Pe and Pc amplitudes of the patients were comparable to those of the controls. In addition, the Ne amplitude, measured at Fcz was positively correlated with the Trail Making Test (TMT), part B response time, and the categories achieved on the Wisconsin Card Sorting Test (WCST) in patients with schizophrenia. No significant correlations were found between Ne amplitude and performance on the neuropsychological tests in the controls. And no associations were detected between CRN, Pe, Pc amplitudes and neuropsychological performance, in either the patients with schizophrenia or the controls. Reduced Ne amplitudes and augmented CRN amplitudes in patients with schizophrenia suggest the dysfunctional behavior-monitoring system in these patients. The functional significances of Ne and Pe are discussed.

Adult↗

PubMed2006

Molecular cloning of rHAUSP encoding a deubiquitinating enzyme in rat testis.

The tumor suppressor protein p53 is stabilized by the herpes-virus-associated ubiquitin-specific protease (HAUSP), a deubiquitinating enzyme. We previously isolated and characterized a mouse orthologue of HAUSP, mHAUSP. In this study, we have identified a rat orthologue of HAUSP, rHAUSP, from the rat testis by RT-PCR using primers used for cloning mHAUSP. rHAUSP cDNA encodes 3,312 bp and 1,103 amino acids with a molecular weight of approximately 135 kDa containing highly conserved Cys, Asp (I), His, and Asn/Asp (II) domains characteristic of the ubiquitin-specific processing proteases. pI value of rHAUSP is 5.31. In vivo and in vitro deubiquitinating enzyme assays demonstrated that rHAUSP has deubiquitinating enzymatic activity. The over-expression of rHAUSP induced cell death of cervical adenocarcinoma cells.

Amino Acid Sequence↗

PubMed2005

The expression patterns of deubiquitinating enzymes, USP22 and Usp22.

Deubiquitinating enzymes regulate a number of cellular mechanisms including pre-implantation, growth and differentiation, oncogenesis, cell cycle progression, transcriptional activation, and signal transduction. In this study, we have identified a novel human deubiquitinating enzyme gene, USP22, and its mouse homologue, Usp22. They encode 525 amino acids (approximate MW: 60kDa) and contains Cys, Asp (I), His and Asp/Asn (II), the highly conserved domains of the UBP family of deubiquitinating enzymes. The biochemical assay revealed that they have deubiquitinating enzyme activity. Northern blot analysis for USP22 showed moderate expression in various organs including human heart and skeletal muscle, and weak expression in lung and liver. However, Usp22 is expressed strongly in brain and weakly in other organs. We investigated the expression level of Usp22 mRNA and the localization during implantation and early pregnancy by in situ hybridization. Interestingly, Northern blot analysis showed the strong expression of Usp22 between embryonic days E10.5 and E12.5. Whole mount in situ hybridization staining revealed that Usp22 was expressed in the midbrain, forebrain, hindbrain and dorsal root ganglia of embryos at E12.5. Embryos at E12.5 showed the pronounced expression of Usp22 during the early embryonic development, although its expression was not detectable in the gut, liver and heart.

Amino Acid Sequence↗

PubMed2005

Activity of left inferior frontal gyrus related to word repetition effects: LORETA imaging with 128-channel EEG and individual MRI.

We investigated the brain substrate of word repetition effects on the implicit memory task using low-resolution electromagnetic tomography (LORETA) with high-density 128-channel EEG and individual MRI as a realistic head model. Thirteen right-handed, healthy subjects performed a word/non-word discrimination task, in which the words and non-words were presented visually, and some of the words appeared twice with a lag of one or five items. All of the subjects exhibited word repetition effects with respect to the behavioral data, in which a faster reaction time was observed to the repeated word (old word) than to the first presentation of the word (new word). The old words elicited more positive-going potentials than the new words, beginning at 200 ms and lasting until 500 ms post-stimulus. We conducted source reconstruction using LORETA at a latency of 400 ms with the peak mean global field potentials and used statistical parametric mapping for the statistical analysis. We found that the source elicited by the old words exhibited a statistically significant current density reduction in the left inferior frontal gyrus. This is the first study to investigate the generators of word repetition effects using voxel-by-voxel statistical mapping of the current density with individual MRI and high-density EEG.

Adult↗

PubMed2005

HAUSP, a deubiquitinating enzyme for p53, is polyubiquitinated, polyneddylated, and dimerized.

The tumor suppressor protein p53 is ubiquitinated and neddylated by MDM2 and then degraded by 26S proteasome. However, p53 is stabilized by the HAUSP (Herpes-virus-associated ubiquitin-specific protease) deubiquitinating enzyme. In this study, we discovered that rat HAUSP (rHAUSP) is polyubiquitinated, polyneddylated, and dimerized using co-immunoprecipitation assays. This suggests that rHAUSP may function as a dimer or multimer and is also degraded through the proteasome-mediated degradation. Transfection of rHAUSP into RGC-Lac-Z cell line with the integrated p53 response element revealed that rHAUSP contributed to p53 stabilization, and a rHAUSP (C224S) mutant contributed to p53 destabilization in a dose-dependent manner.

Animals↗

PubMed2005

Implicit and explicit memory in patients with obsessive-compulsive disorder: an event-related potential study.

The implicit and explicit memory in patients with obsessive-compulsive disorder (OCD) was investigated using the event-related potential (ERP). For the assessment of implicit memory, a lexical decision task was administered. Among a total of 320 words and 140 non-words, 200 words were repeated, while the remaining 120 words and the 140 non-words were not repeated. For explicit memory, a continuous recognition task was administered, in which 280 words were repeated and 100 were not repeated. On the recognition task, both the controls and OCD patients showed more positivity to the old words than to the new words during the 200-600 ms period post-stimulus. Both groups showed faster response time to the old words than to the new words. On the lexical decision task, the controls showed the old/new effect during the 200-500 ms period post-stimulus, while the OCD patients did not. However, OCD patient showed faster response time to the old words than to the new words, although OCD patients showed prolonged response times to the old words compared to the controls. These results indicate that OCD patients have preserved explicit and implicit memory. The absence of old/new effect on ERP in OCD patients was discussed in terms of dysfunction of frontostriatal system, which plays an important role in both OCD and implicit memory.

Adult↗

PubMed2005

Deubiquitinating enzyme USP36 contains the PEST motif and is polyubiquitinated.

The ubiquitin-mediated protein degradation pathway has been emphasized for the regulation of numerous cellular mechanisms and the significance of deubiquitination, mediated by deubiquitinating (DUB) enzymes, has been emerging as an essential regulatory step to control these cellular mechanisms. Previously, we demonstrated a human DUB enzyme, HeLa DUB-1, expressed in human ovarian cancer cells. Here, we report human USP36, which has the extension of the C-terminal region of HeLa DUB-1 and has conserved amino acid domains as previously shown in other DUBs. Human USP36, encoding a DUB enzyme, was isolated from ovarian cancer cells using RT-PCR and characterized. We identified DUB enzyme activity of USP36 by analyzing its capability to cleave the ubiquitin. Interestingly, structural and immunoprecipitation analyses revealed for the first time that USP36 contains the PEST motif and is polyubiquitinated.

Amino Acid Motifs↗

PubMed2005

Persistent cognitive dysfunction in patients with obsessive-compulsive disorder: a naturalistic study.

The purpose of the present study was to investigate the changes in the cognitive dysfunctions of patients with obsessive-compulsive disorder (OCD) over a 1-year period of pharmacological treatment. Twenty-one OCD patients and 20 normal subjects underwent neuropsychological tests and clinical evaluations on three separate occasions (baseline, 4 months, and 1 year after the start of medications). OCD patients continued to show significant impairments in the following cognitive measures compared with the normal controls: accuracy of immediate and delayed recall on the Rey-Osterrieth complex figure tests, the numbers of responses on the category fluency test, the response time on the trail making test--part A, and the number of perseverative response and perseverative errors on the Wisconsin card sorting test. The findings in this study suggested that impaired performance on cognitive domains, such as visuospatial memory and verbal fluency may underline the pathology of OCD.

Adult↗

PubMed2004

Murine Asb-17 expression during mouse testis development and spermatogenesis.

In this study we isolated a murine mAsb-17 from mouse testis by RT-PCR using primers designed based on the sequences from the GenBank database. The sequence analysis showed that mAsb-17 encodes a 295 amino acid polypeptide with a molecular weight of approximately 34 kDa containing two ankyrin repeats and one SOCS box. The amino acid sequence of mASB-17 showed 87.5%, 98.3% and 92.9% identity with that of human, rat and dog, respectively. Interestingly, northern blot analysis showed that mAsb-17 was expressed only in the testis. The expression analysis by RT-PCR for mAsb-17 in mouse indicates that mAsb-17 is expressed from the fourth week after birth to adult, with the highest expression in round spermatids. Both northern blot and RT-PCR analyses suggest that mASB-17 may play essential roles in testis development and spermatogenesis.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Impairment of recognition memory in schizophrenia: event-related potential study using a continuous recognition task.

Recognition memory and the dissociation of immediate and delayed repetition in schizophrenic patients were investigated using event-related potential (ERP) and a continuous word recognition task. In total, 14 schizophrenic patients and 14 age and gender-matched control subjects, were recruited. Among 240 stimulus words used, 40 words were not repeated, 100 were repeated immediately, and 100 were repeated after five intervening words. Both schizophrenic and control groups responded faster to words repeated immediately than to words repeated after a delay and to new words. However, schizophrenic patients responded less accurately to words repeated immediately and to words repeated after a delay than the controls. In terms of ERP, schizophrenic patients showed significantly reduced N200, late positive component (LPC), and N400 amplitudes, and a more frontally-distributed N200 topography than the controls. For controls, immediate repetition was associated with a large LPC amplitude and the absence of N400, while delayed repetition was associated with a small LPC amplitude and the presence of N400. However, this dissociation between immediate and delayed repetition was not observed in schizophrenic patients. All of these results suggest that schizophrenic patients have recognition memory impairment, the cause of which may range from early encoding, and memory search to late retrieval.

Adult↗

PubMed2004

A novel cysteine protease HeLa DUB-1 responsible for cleaving the ubiquitin in human ovarian cancer cells.

The regulation of ubiquitin-mediated protein degradation is becoming important for a number of cellular processes. Human HeLa DUB-1 cDNA, encoding a novel deubiquitinating enzyme, was isolated from ovarian cancer cells. It has 1,647 bp nucleotides and encodes a 548 amino acid polypeptide with the molecular weight of approximately 61 kDa. It contains the highly conserved Cys, Asp (I), His, and Asn/Asp (II) domains characteristic of the ubiquitin-specific processing proteases. Biochemical assay revealed that HeLa DUB-1 has deubiquitinating enzyme activity in vivo and in vitro. Northern blot analysis for HeLa DUB-1 showed the strong expression in human skeletal muscle and pancreas and to some extent in heart, placenta, lung, liver, and kidney. Interestingly, the expression was hardly seen in the brain. Localization study indicates that HeLa DUB-1 proteins are present in both the cytoplasm and nucleus.

Amino Acid Sequence↗

PubMed2003

DUB-1A, a novel deubiquitinating enzyme subfamily member, is polyubiquitinated and cytokine-inducible in B-lymphocytes.

Recently, we isolated the Dub-2A gene, which encodes a novel murine deubiquitinating enzyme subfamily member, from a bacterial artificial chromosome library clone by PCR amplification with degenerate PCR primers for the Dub-2 cDNA (Baek, K.-H., Mondoux, M. A., Jaster, R., Fire-Levin E., and D'Andrea, A. D. (2001) Blood 98, 636-642). In this study, we analyzed two more clones from the library to isolate genes encoding other deubiquitinating enzymes. Dub-1A, which encodes the shortest member of the DUB subfamily of deubiquitinating enzymes so far, has been identified in both clones and characterized. Sequence analysis showed that Dub-1A encodes a 468-amino acid protein that has a molecular mass of approximately 51 kDa and that contains a putative catalytic domain (Cys, His, and Asp) conserved among DUB proteins. The amino acid sequence of DUB-1A is 84.5, 84.7, and 85.3% identical to those of DUB-1, DUB-2, and DUB-2A, respectively. Reverse transcription-PCR revealed that Dub-1A is expressed not only in B-lymphocytes in response to interleukin-3 stimulation, but also in T-lymphocytes, brain, heart, liver, lung, kidney, ovary, and spleen. This suggests that Dub-1A may play essential roles in each of these organs. In vivo and in vitro deubiquitinating enzyme assays showed that DUB-1A has functional deubiquitinating activity and that the 5'-flanking sequence of Dub-1A has a functional enhancer domain as shown in Dub-1 and Dub-2A. Interestingly, immunoblot analysis revealed that DUB-1A is polyubiquitinated, indicating that it is degraded through proteasome-mediated degradation. In the absence of JAK2, Dub-1A was expressed at a lower level. This suggests that DUB-1A functions downstream of JAK2 kinase in the interleukin-3 signaling pathway.

Amino Acid Sequence↗

PubMed2003

Neuropsychological correlates of P300 abnormalities in patients with schizophrenia and obsessive-compulsive disorder.

The cognitive significance of P300 abnormalities in schizophrenia and obsessive-compulsive disorder (OCD) was investigated. P300 was measured by an auditory oddball paradigm, in which a series of standard tones (1000 Hz) and target tones (1500 Hz) were presented. The subject's task was to count the number of the presented target tones. Cognitive functions were evaluated by neuropsychological tests, which were chosen to be sensitive to frontal and temporal dysfunction. Twenty-two schizophrenic patients, 19 OCD patients and 21 healthy controls participated. Event-related potentials measured at 15 electrode sites, which consisted of five levels on the left-right dimension and three levels on the anterior-posterior dimension, were included in the statistical analysis. P300 amplitudes on all 15 electrode sites were significantly smaller in schizophrenic and OCD patients than in the controls. Schizophrenic patients performed poorly on almost all neuropsychological tests, while OCD patients showed impaired performance on the Rey-Osterrieth Complex Figure Test and on a controlled oral word association test. In schizophrenic patients, P300 amplitude was associated with performance on verbal memory and learning by the Luria-Nebraska Neuropsychological Battery, while for OCD patients, P300 amplitude was related to the Trail Making Test, Part B response time. These results indicate that schizophrenic patients have generalized cognitive impairments, which are substrated by a wide range of cortical dysfunctions. The major cognitive deficits observed in OCD patients were impairments of controlled attention and self-guided, flexible behavior, which are mediated by the fronto-striatal system. The neurophysiological mechanisms underlying P300 abnormalities observed in schizophrenic and OCD patients are discussed.

Acoustic Stimulation↗