Biomedical subjects

Pil-Woo Huh

Publications and source records attributed to Pil-Woo Huh.

10 recordsLinked to original sources

PubMed2006

Surgical results in pediatric moyamoya disease: angiographic revascularization and the clinical results.

OBJECTIVE: We retrospectively reviewed the pediatric patients with moyamoya disease (MMD) who underwent bypass surgery at our institution to compare the surgical results according to the surgical procedures. PATIENTS AND METHODS: There were 24 total patients (age range: 2-15 years; mean age: 8.2 years). Twelve patients underwent encephalo-duro-arterio-synangiosis (EDAS) on 16 sides, 5 patients underwent encephalo-duro-arterio-myo-synangiosis (EDAMS) on 8 sides and 7 patients underwent combined superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis with EDAMS (STA-MCA-EDAMS) on 12 sides. The postoperative results were evaluated between 4 months and 5 years following surgery in terms of the angiographic revascularization and the clinical outcome. RESULTS: EDAMS, regardless of the combined STA-MCA anastomosis, was significantly effective for achieving a good extent of the postoperative angiographic revascularization as compared with simple EDAS (P<0.05). STA-MCA-EDAMS tended to be better with respective to the relief of preoperative ischemic symptoms as compared with simple EDAS, although there was no significant statistical difference. CONCLUSION: These results suggest that EDAMS with or without the combination of STA-MCA anastomosis was very useful for the formation of collateral circulation in comparison with simple EDAS for treating the pediatric patients with MMD, although these findings were not well correlated with the clinical outcomes.

Adolescent↗

PubMed2006

Combined direct anastomosis and encephaloduroarteriogaleosynangiosis using inverted superficial temporal artery-galeal flap and superficial temporal artery-galeal pedicle in adult moyamoya disease.

BACKGROUND: We evaluated the efficacy of combined STA-MCA anastomosis and EDAGS using inverted STAGF and STAGP for the treatment of adult MMD. METHODS: This study included 8 patients with nonhemorrhagic MMD. There were 6 women and 2 men who were between 23 and 62 years old (mean = 37.8 years) in the sample. The combined surgery was performed on 12 sides in the 8 patients. The surgical results were assessed for clinical outcome, angiographic revascularization, and hemodynamic change on HMPAO brain SPECT. The follow-up period ranged from 6 to 62 months (mean = 27 months). RESULTS: Clinical symptoms and signs were improved or stabilized, and the extent of revascularization evident on external carotid angiograms was excellent in all 8 patients. The CBF on HMPAO SPECT also improved in all 12 sides that were operated on with the combined surgery, except for the preexisting infarcted area, on the basal as well as Diamox stimulation studies. One patient had a transient speech disturbance after surgery, and another patient had delayed wound healing. CONCLUSIONS: The combined STA-MCA anastomosis and EDAGS using inverted STAGF/P seems to be one of the most effective surgical modalities for the treatment of nonhemorrhagic MMD in adults.

Adult↗

PubMed2006

Diagnostic method for differentiating external hydrocephalus from simple subdural hygroma.

OBJECT: The various terms used to describe subdural fluid collection--"external hydrocephalus", "subdural hygroma", "subdural effusion", "benign subdural collection", and "extraventricular obstructive hydrocephalus"-reflect the confusion surrounding the diagnoses of these diseases. Differentiating external hydrocephalus from simple subdural hygroma may be difficult, but the former appears to be a distinct clinical entity separate from the latter. In this report, the authors present a diagnostic method for differentiating external hydrocephalus from simple subdural hygroma, based on their clinical experience in treating subdural fluid collection after mild head trauma. METHODS: Twenty patients with subdural fluid collection after mild head trauma were included in this study. Ventricle size was measured using a modified frontal horn index (mFHI); that is, the largest width of the frontal horns divided by the bicortical distance in the same plane, instead of the inner table distance. Bur hole trephination was performed on the appearance of a subdural fluid collection thicker than 15 mm on computed tomography (CT), persistent (longer than 4 weeks) or increasing in size, and accompanied by neurological symptoms (confusion or memory impairment). During the procedure, subdural pressure was measured using a manometer before opening the dura mater. Subdural pressure varied among the patients, ranging from 3 to 27.5 cm H2O. Four patients with a subdural pressure greater than 15 cm H2O had hydrocephalus after surgery (p < 0.05). Hydrocephalus developed in a pediatric patient (2 years old) with a subdural pressure of 12 cm H2O. All of the patients in whom hydrocephalus developed after bur hole trephination had had enlarged ventricles (mFHI > 33%) on preoperative CT scans. CONCLUSIONS: Monitoring subdural pressure may be a valuable tool for differentiating subdural hygroma from external hydrocephalus in patients with mild head trauma. Additionally, the mFHI reflects the nature of the subdural collection more accurately than the standard frontal horn index.

Adolescent↗

PubMed2004

MAP, a protein interacting with a tumor suppressor, merlin, through the run domain.

Merlin (or schwannomin) is a tumor suppressor encoded by the neurofibromatosis type 2 gene. Many studies have suggested that merlin is involved in the regulation of cell growth and proliferation through interactions with various cellular proteins. To better understand the function of merlin, we tried to identify the proteins that bind to merlin using the yeast two-hybrid screening. Characterization of the positive clones revealed a protein of 749 amino acids named merlin-associated protein (MAP), which showed wide tissue distribution in Northern blot analysis. Sequence analysis revealed that MAP is a potential homologue of a yeast check-point protein, BUB2, and contains TBC, SH3, and RUN domains, thereby implicating its role in the Ras-like GTPase signal pathways. MAP and merlin were directly associated in vitro and in vivo, and colocalized in NIH3T3 cells. The RUN domain of MAP and the C-terminus of merlin appeared to be responsible for their interaction. MAP decreased the AP-1-dependent promoter activity additively with merlin in NIH3T3 cells. In addition, merlin and MAP synergistically reduced the colony formation of NIH3T3 cells. These results suggest that MAP may play a cooperative role in the merlin-mediated growth suppression of cells.

3T3 Cells↗

PubMed2004

Merlin, a tumor suppressor, interacts with transactivation-responsive RNA-binding protein and inhibits its oncogenic activity.

The neurofibromatosis type 2 gene-encoded protein, merlin, is related to the ERM (ezrin, radixin, and moesin) family of membrane-cytoskeleton-associated proteins. Recent studies suggest that the loss of neurofibromatosis type 2 function contributes to tumor development and metastasis. Although the cellular functions of merlin as a tumor suppressor are relatively well characterized, the cellular mechanism whereby merlin controls cell proliferation from membrane locations is still poorly understood. During our efforts to find potential merlin modulators through protein-protein interactions, we identified transactivation-responsive RNA-binding protein (TRBP) as a merlin-binding protein in a yeast two-hybrid screen. The interaction between TRBP and merlin was confirmed by glutathione S-transferase pull-down assays, co-immunoprecipitation, and co-localization experiments. The carboxyl-terminal regions of each protein were responsible for their interaction. Cells overexpressing TRBP showed enhanced cell growth in cell proliferation assays and also exhibited transformed phenotypes, such as anchorage-independent cell growth and tumor development in mouse xenografts. Merlin efficiently inhibited these oncogenic activities of TRBP in our experiments. These results provide the first clue to the functional interaction between TRBP and merlin and suggest a novel mechanism for the tumor suppressor function of merlin both in vitro and in vivo.

Agar↗

PubMed2003

Merlin neutralizes the inhibitory effect of Mdm2 on p53.

The stability of p53 tumor suppressor is regulated by Mdm2 via the ubiquitination and proteasome-mediated proteolysis pathway. The c-Abl and PTEN tumor suppressors are known to stabilize p53 by blocking the Mdm2-mediated p53 degradation. This study investigated the correlation between p53 and merlin, a neurofibromatosis 2 (NF2)-related tumor suppressor, in association with the Mdm2 function. The results showed that merlin increased the p53 stability by inhibiting the Mdm2-mediated degradation of p53, which accompanied the increase in the p53-dependent transcriptional activity. The stabilization of p53 by merlin appeared to be accomplished through Mdm2 degradation, and the N-terminal region of merlin was responsible for this novel activity. This study also showed that overexpression of merlin-induced apoptosis of cells depending preferentially on p53 in response to the serum starvation or a chemotherapeutic agent. These results suggest that merlin could be a positive regulator of p53 in terms of tumor suppressor activity, and provide the promising therapeutic means for treating tumors with non-functional merlin or Mdm2 overexpression.

Animals↗

PubMed2003

Amyloid beta peptide (Abeta42) activates PLC-delta1 promoter through the NF-kappaB binding site.

The abnormal deposition of amyloid beta peptide (Abeta) is a hallmark of Alzheimer's disease (AD). Phospholipase C-delta1 (PLC-delta1) is also known to abnormally accumulate in the brains of AD patients, but no report has addressed the relationship between these two events. This study investigated the effect of Abeta42 on the PLC-delta1 expression in human neuroblastoma cell lines. The PLC-delta1 mRNA level was increased by treatment with Abeta42 in a RT-PCR analysis. In the reporter assay, Abeta42 was found to activate the PLC-delta1 promoter activity in a dose-dependent manner. A novel NF-kappaB binding site in the PLC-delta1 promoter appeared to be responsible for the Abeta42 activity. First, the dominant negative forms of the NF-kappaB activating molecules, dominant negative TGF-beta activated kinase 1 (dnTAK1) and dnNIK (dominant negative NF-kappaB-inducing kinase), abolished the Abeta42 activity in the reporter assay. Second, the Abeta42 augmented a factor binding on the NF-kappaB site in the electrophoretic mobility shift assay (EMSA), which was abolished by a molar excess of the unlabeled consensus NF-kappaB oligonucleotide. These results suggest that the PLC-delta1 promoter is under the control of NF-kappaB, which mediates the expression of PLC-delta due to the Abeta42 treatment.

Amyloid beta-Peptides↗

PubMed2003

Merlin suppresses the SRE-dependent transcription by inhibiting the activation of Ras-ERK pathway.

The neurofibromatosis type 2 (NF2) gene encodes an intracellular membrane-associated protein called merlin or schwannomin, which is known to be a tumor suppressor. Numerous studies have suggested that merlin is involved in the regulation of cell growth and proliferation. Previously, merlin/schwannomin was reported to block Ras-induced cell proliferation and anchorage-independent cell growth. Also, the N-terminus of merlin was found to suppress cell proliferation, although it appears to be less effective than full-length merlin. However, the inhibitory mechanism of merlin is unknown. In this report, merlin is shown to be effective at suppressing serum/Ras-induced and Elk-mediated SRE dependent transactivation, and serum-induced ERK phosphorylation in NIH3T3 cells. In addition, merlin inhibited serum-induced Elk phosphorylation, a downstream effector of ERKs. Also, the N-terminal deficient merlin mutant could not block serum-induced and Elk-mediated SRE dependent transactivation, although the C-terminal deficient merlin mutant could. These results suggest that merlin inhibits SRE dependent transactivation by repressing serum-induced ERK phosphorylation and its downstream effector, Elk phosphorylation. Also, the N-terminus of merlin may be important for its inhibitory effect. Our results show that merlin acts as a negative regulator of the SRE signaling pathway via the Ras-ERKs pathway.

3T3 Cells↗

PubMed2003

Associations of Moyamoya patients with HLA class I and class II alleles in the Korean population.

Moyamoya disease is characterized by progressive cerebrovascular occlusion at the peripheral internal carotid artery and development of abnormal collateral circulation at the cerebral basal region. Although abnormal thrombogenesis, inflammation and autoimmune process might be involved in the etiology, the genetic pathogenesis of Moyamoya disease is still unknown. To evaluate the association of Moyamoya disease with HLA alleles in the Korean population, we investigated HLA class I and class II alleles in 28 Moyamoya patients and 198 unrelated healthy controls. The frequency of HLA-B35 allele was significantly increased in the patients compared to the controls (32.1% vs. 10.1%, RR=4.2, p<0.008). Further analysis of HLA-B35 on onset age and sex showed that this allele was significantly increased compared to the controls in both late-onset and female group. Especially, HLA-B35 was the most significantly increased in female of late-onset group compared to the controls. These results suggest that HLA-B35 may be an useful genetic marker for Moyamoya disease, and particularly in females of late onset group in the Korean population.

Adolescent↗

PubMed2002

Identification of the elements regulating the expression of the phospholipase C delta1.

Recently we cloned the phospholipase C deltal (PLC-delta1) promoter region and found that PLC-delta1 is selectively expressed in several tissues. In order to establish the common and cell-type specific transcriptional elements, 1.8 kilobase of the 5'-flanking region of PLC-delta1 was characterized in several cell lines. A transient transfection assay of the -1787-Luc construct in several cell lines demonstrated the potential transcriptional enhancement of reporter activities in the neuroblastoma cell [SK-N-BE(2)C] and kidney cell lines (Cos-7), but not in liver cell lines (Chang liver cell). Transient transfection assays of a series of 5' --> 3' deletion constructs of the PLC-delta1 promoter and electronic mobility shift assays suggested that the E-box and HFH3 binding sites are cell-type specific elements, and that Sp-1 is a major transcriptional activator of a majority of cell lines. Our findings, therefore, indicate that the combination of several elements within the 5'-flanking region of the PLC-delta1 gene dictates its restricted expression in several cell lines.

5' Flanking Region↗