Biomedical subjects

Hyung-Seok Kim

Publications and source records attributed to Hyung-Seok Kim.

14 recordsLinked to original sources

PubMed2006

Eye field requires the function of Sfrp1 as a Wnt antagonist.

Wnts have been shown to provide a posteriorizing signal that has to be repressed in the specification of vertebrate forebrain region. Previous studies have shown that Wnt activation by LiCl treatment causes an expansion of optic stalk and mid-hindbrain boundary, whereas eye and ventral diencephalon in the forebrain region were reduced. However, the molecular mechanism, by which inhibits Wnt activity in the forebrain remains poorly defined. To investigate relationship between forebrain specification and Wnt signaling, the zebrafish homologue of secreted frizzled related protein1 (sfrp1) has been characterized. The transcripts of sfrp1 are detected in the presumptive forebrain at gastrula and in the ventral telencephalon, ventral diencephalon, midbrain and optic vesicles at 24h after postfertilization (hpf). Overexpression of sfrp1 causes an anteriorization of embryo, with enlarged head and reduced posterior structure as in the embryo overexpressing dominant-negative form of Frizzled8a or Dkk1. Its overexpression restored the eye defects in the Wnt8b-overexpressing embryos, but not in the LiCl-treated embryos. These results suggest that Sfrp1 expressed in the forebrain and eye field plays a critical role in the extracellular events of antagonizing Wnt activity for the forebrain specification.

Animals↗

PubMed2006

Maspin expression in early oral tongue cancer and its relation to expression of mutant-type p53 and vascular endothelial growth factor (VEGF).

Even though oral tongue cancer is generally diagnosed at an early stage, the prognosis is poor due to frequent recurrence. Therefore, it is important to identify factors predictive of recurrence and to treat aggressively those patients with a high probability of recurrence. The relationship between angiogenesis and recurrence in tongue cancer has been widely investigated but no consensus has been reached. Mutant-type p53 and VEGF are known to be related to angiogenesis, and maspin is a potent angiogenic inhibitor but its role in tongue cancer has scarcely been examined. We observed the expression of maspin, mutant-type p53 and VEGF by immunohistochemistry in 33 patients with stages I and II oral tongue cancer. And the relationships between maspin, mutant-type p53, VEGF expression and recurrence were analyzed. Maspin and VEGF displayed a cytoplasmic staining pattern and mutant-type p53 a nuclear pattern. None of expression of maspin, mutant-type p53, and VEGF was significantly correlated with tumor recurrence (p=0.34, 0.56, and 0.33, respectively) and survival. Maspin expression was negatively correlated with both mutant-type p53 expression (p=0.02), and VEGF expression (p=0.01). There was no correlation between age, sex, clinical staging, and recurrence. In conclusion, the expression of maspin is not related to recurrence of early stage oral tongue cancer. It is inversely correlated with that of mutant-type p53 and of VEGF, suggesting that the maspin gene is a mutant-type p53 target in vivo and may contribute to regulate VEGF expression.

Adult↗

PubMed2006

Fluorescent protein expression driven by her4 regulatory elements reveals the spatiotemporal pattern of Notch signaling in the nervous system of zebrafish embryos.

Notch activation inhibits neuronal differentiation during development of the nervous system; however, the dynamic role of Notch signaling in individual cell lineages remains poorly understood. We have characterized 3.4 kb 5'-regulatory sequence of a Notch target gene, her4, and used it to drive fluorescent gene expression in transgenic lines where the spatiotemporal pattern of Notch activation can be examined in vivo. The 3.4 kb her4 promoter contains five predicted Su(H) binding sites of which two proximal sites were confirmed to be required for Notch-mediated transcriptional activation. Without Notch, Su(H) effectively represses transcription regulated by the promoter. Analyses of transgenic zebrafish showed that while the expression of proneural genes and Notch activation were both critical for endogenous her4 expression, reporter gene expression was primarily regulated by Notch activity. This study also showed that her4 may be differently regulated in sensory cranial ganglia, where Notch activity is not essential for her4 expression and where Su(H) may repress her4 expression. The establishment of a reporter line with Notch-Su(H)-dependent fluorescent gene expression provides a tool to explore the complex role of Notch signaling in the development of vertebrate nervous system.

Animals↗

PubMed2006

Clinical features and epileptogenesis of dysembryoplastic neuroepithelial tumor.

INTRODUCTION: Dysembryoplastic neuroepithelial tumor (DNT) frequently causes medically intractable epilepsy. OBJECTIVE: The aim of this study was to investigate the basic mechanism of epileptogenecity of the tumor. MATERIALS AND METHODS: Clinicopathological data in 13 cases of DNT and immunohistochemical changes of ionotropic glutamate receptor subunits in the tumor and peritumoral epileptogenic cortex were studied. CONCLUSIONS: Magnetic resonance imaging combined with electroencephalography (EEG), electrocorticography, and depth-electrode EEG was valuable to localize complicated epileptogenic zones of the patients with DNT. Neuropathological examinations of the peritumoral cerebral cortex presenting abnormal spikes showed different histopathological grades of neuronal migration disorder (NMD). The tumor cells in DNT disclosed increased immunopositivities of N-methyl-D: -aspartate receptor 1 (NR1) and NR2A/B, and peritumoral epileptogenic NMD revealed increased immunopositivities of GluR2 and GluR3. The amplification of ionotropic glutamate receptor subunits in the tumor and peritumoral NMD may be the underlying cause of epileptic seizures in DNT patients.

Adolescent↗

PubMed2006

CDX-2 homeobox gene expression in human gastric carcinoma and precursor lesions.

BACKGROUND: Recent studies have demonstrated that CDX-2 is expressed in the intestinal metaplasia of the stomach and intestinal-type gastric cancer. To address the role of CDX-2 in carcinogenesis of gastric carcinomas of intestinal type, the expression of CDX-2 in gastric carcinoma and precursor lesions were examined using immunohistochemistry. METHODS: A total of 160 specimens diagnosed as gastric carcinomas or non-invasive neoplasia from 158 patients were analyzed for CDX-2 expression by immunochemical methods. Patients were classified into histopathologic subgroups according to the Padova international classification: 60 cases of low-grade non-invasive neoplasia, 55 cases of high grade, and 45 cases of invasive intestinal-type adenocarcinoma. The CDX-2 expression in non-neoplastic gastric mucosa including intestinal metaplasia was also evaluated in the areas included in the histologic sections. RESULTS: The CDX-2 expression was localized in the epithelial cell nuclei in the area of intestinal metaplasia with or without dysplasia and carcinoma, consistent with its role as a transcriptional regulator. No CDX-2 reactivity was noted in the normal mucosa in all cases. The CDX-2 expression was detected in 73.3% of low-grade cases, 85.5% of high-grade cases and 91.1% of intestinal-type adenocarcinoma cases. In the gastric mucosa with intestinal metaplasia, 89.7% of the samples were positive. The CDX-2-expressing cells in intestinal metaplasia were more prevalent than in dysplasia and carcinoma. Expression of CDX-2 showed a statistically significant positive correlation with increasing grade of dysplasia and carcinoma. CONCLUSIONS: These findings suggest that CDX-2 expression in stomach cancer may be a marker of the progression of gastric carcinogenesis, and that its activation may represent an early event.

Adenocarcinoma↗

PubMed2006

Bilateral perisylvian ulegyria: clinicopathological study of patients presenting with pseudobulbar palsy and epilepsy.

Structural abnormalities related with pseudobulbar palsy have been gaining attention because of their characteristic symptoms and unique pathogenesis. We present five cases of bilateral perisylvian ulegyria (BPU) presenting epilepsy and pseudobulbar palsy with pathogenesis different from previously reported syndromes. All patients showed medically intractable seizures, complex partial seizures with secondary generalization and clinical symptoms of pseudobulbar palsy, including dysarthria, limitation of tongue movement and drooling. MRI revealed BPU in all patients, and BPU associated with hippocampal sclerosis in four patients. Intracranial EEG recording with subdural grip and stripe was helpful for localizing the area of ictal generation. Resective surgeries, including the temporal lobe, central area and parietal lobe, were performed depending on the localizing information. The surgical outcome was favorable after 9.8 years of follow-up. Characteristic features of ulegyria were confirmed on pathological examination. Ulegyria is considered to be another important perinatal or postnatal structural abnormality which can explain the etiological heterogeneity for pseudobulbar palsy, which results from bilateral perisylvian lesions. Awareness of this disorder can provide a useful strategy for evaluation and treatment which differs from that in perisylvian polymicrogyria.

Adult↗

PubMed2005

Epstein-Barr virus infected natural killer cell lymphoma in a patient with hypersensitivity to mosquito bite.

Hypersensitivity to mosquito bite (HMB) can occur in association with chronic Epstein-Barr virus (EBV) infection and natural killer (NK) cell leukaemia/lymphoma, which was named 'Tokura-Ishihara disease'. This disease is very rare and most previous reports have been documented in Japan. We present a patient who suffered from of pustules on skin, high fever, myalgia and multiple lymph node enlargements after mosquito bite from childhood. Recently, multiple lymph nodes were palpable on his both inguinal area. Peripheral blood smear (PBS) revealed many large granular lymphocytes and the skin lesion showed a dense dermal and subcutaneous infiltrate of lymphocytes. The lymph nodes and perinodal adipose tissue were infiltrated by atypical lymphoid cells in which EBER-positive signals were identified by in situ hybridization using EBV encoded RNA-1 probe. He was diagnosed as having Tokura-Ishihara disease and receives chemotherapy now. Here, we report a case of this disease with a precise pathological description on the lymph node biopsy.

Adult↗

PubMed2005

Efficacy assessment of CellSlide in liquid-based gynecologic cytology.

OBJECTIVE: To evaluate the efficacy of CellSlidetrade mark (CS) method in liquid-based gynecologic cytology. METHODS: We compared 1221 specimens prepared by both CS and conventional techniques to evaluate specimen adequacy and cytologic diagnoses. Sensitivity and specificity of these techniques were analyzed in 54 cases using the available histological data. RESULTS: Quality limiting factors, such as obscuring inflammation or blood, were markedly reduced in CS (0.2%) compared to the conventional smear (4.9%). There was a complete agreement in the Bethesda 2001 diagnosis between these methods in 1132 cases (92.7%) out of 1221. 16.7% more ASC cases and 37.5% more low-grade squamous intraepithelial lesions (LSIL) and 21.4% more high-grade SIL (HSIL) were detected on the CS slides than on the conventional smears. Sensitivity rates, relative to histological data, were 91.4% (CS) and 74.3% (conventional) and specificity rates were same (89.5%) for ASC and more severe lesions. Infectious organisms (Trichomonas and Candida, etc.) were readily identifiable in both methods. CONCLUSIONS: CS preparation is more sensitive and equally specific in detecting epithelial abnormalities when compared to the conventional smear. In addition, it has a lower incidence of unsatisfactory results with hypocellularity or >75% obscuration of cells.

Carcinoma, Squamous Cell↗

PubMed2004

A comparison of modified MonoPrep2 of liquid-based cytology with ThinPrep Pap test.

OBJECTIVE: The purpose of this study is to evaluate a modified MonoPrep2 (MP) of liquid-based cytology (LBC) to search for a less expensive alternative technique usable for screening of cervical cancers. STUDY DESIGN: Cervicovaginal direct-to-vial samples from 1218 consecutive patients were processed with the modified MP technique and the results were compared with those of currently popular ThinPrep Pap test (TP) technique. RESULTS: Both MP and TP methods provide uniformly spread thin layers of cells without cellular overlap or significant obscuring elements. The diameter of the circular area was 20 mm in MP and 22 mm in TP. Obscuring factors were slightly more frequent in MP but not enough to affect interpretation. Thirteen specimens were excluded from the study because of poor specimen quality in MP. In 1205 patients, there was an absolute agreement in results (the Bethesda diagnosis system) between the two methods, and discordances were observed in only 18 (1.5%) in 1187 cases (98.5%). Furthermore, there was no significant difference in diagnostic accuracy in histopathologic correlation between the two methods. The sensitivity of MP was slightly lower than that of TP, and the specificity of MP was higher than that of TP. A human papillomavirus (HPV) test with polymerase chain reaction (PCR) using broad-spectrum probes has yielded good results in both MP and TP samples. CONCLUSIONS: The modification of the MP method gave comparable results to those of TP in terms of smear quality, cytologic diagnostic evaluation, and biopsy correlation with much less cost. The modified MP offers a cost-effective alternative to the currently popular expensive techniques of liquid-based cytology practical for cervical cancer screening.

Female↗

PubMed2003

Characterization and expression of a presomitic mesoderm-specific mespo gene in zebrafish.

A complete zebrafish mespo cDNA encoding a protein of 131 amino acids with a bHLH domain in the C-terminal has been isolated. The bHLH domain of zebrafish Mespo is highly similar to those in the mouse, chick and Xenopus, sharing 82.4%, 80.4% and 74.5% amino acid identity, respectively. At 50% epiboly, the zebrafish mespo is first detected in the marginal zone of the blastoderm but excluding the prospective shield. Subsequently, mespo expression is intensified in the involuting mesoderm at 60% epiboly, and then restricted to the presomitic mesoderm (PSM) at 95% epiboly. At the 1-somite stage, mespo expression becomes reduced in the most rostral PSM. During segmentation, mespo expression is gradually downregulated at the most rostral segmental plate where cells are being coalesced to form somites. In spadetail mutant embryos, most of mespo-expressing cells were missing.

Amino Acid Sequence↗

PubMed2003

Correlation between cyclooxygenase-2 and tumor angiogenesis in non-small cell lung cancer.

The role of COX-2 expression and angiogenesis of lung cancer is yet to be delineated. Eighty four non-small cell lung cancer (NSCLC) specimens were evaluated for COX-2 expression, microvessel density (MVD), and vascular endothelial growth factor (VEGF) expression by immunohistochemical methods. The relationships between COX-2 expression and MVD, VEGF expression, and survival time were analyzed. COX-2 expression was observed in the cytoplasm and membrane of the carcinoma cells, and premalignant cells. COX-2 was positive in 67 cases (79.8%). There was a statistically significant correlation between COX-2 expression and tumor size, TNM stage, tumor type, VEGF expression, and vascular pattern with survival in univariate analysis. No significant correlation was seen between COX-2, VEGF expression and MVD. A lack of expression of either COX-2 or VEGF expression or both, however, was associated with lower MVD than the group with both expressed. The difference was statistically significant (P=0.005). Statistically significant differences were also observed according to TNM stage, vascular pattern, COX-2 expression, and VEGF expression. With multivariate analysis, only TNM stage and COX-2 expression retained their significance as independent predictors of survival. COX-2 expression takes part in tumor angiogenesis and is a significant poor prognostic factor in the surgically resected NSCLC. COX-2 inhibitor, either in combination therapy with other agents, or for chemoprevention, may be effective via suppression of angiogenesis in this fatal disease.

Adult↗

PubMed2002

Isolation and expression of a novel neuron-specific onecut homeobox gene in zebrafish.

A complete cDNA of a novel zebrafish gene named onecut has been isolated; this gene encodes a protein of 446 amino acids with a Cut domain (73 amino acid residues) and a homeodomain. The Cut domain of zebrafish Onecut is highly similar to those in mammalian hepatocyte nuclear factor-6 and Drosophila Onecut, sharing 90 and 88% amino acid identity, respectively. The expression of zebrafish onecut is restricted to neuronal cells, being first detected in trigeminal ganglia neurons at the end of gastrulation. By the 1-somite stage, onecut expression has begun in primary neurons of the lateral stripes in the neural plate, and appeared in neuronal cells of the medial stripes at the 2-somite stage. By the 4-somite stage, onecut expression expanded to the intermediate stripes and to subsets of neuronal cells in the midbrain and hindbrain. Subsequently, onecut expression intensified in the lateral region of midbrain and hindbrain, yet no onecut-positive cells were seen in the telencephalon. By 24hpf, onecut transcripts remained abundant in the spinal cord but were no longer detectable in differentiated Rohon-Beard sensory neurons. The expression of onecut was greatly increased in the neural mutant mindbomb, while being decreased in narrowminded.

Animals↗

PubMed2002

Comparative evaluation of angiogenesis in gastric adenocarcinoma by nestin and CD34.

Tumor angiogenesis has been shown to be important for growth and metastasis in human neoplasms. Angiogenesis is usually determined by immunohistochemical staining of tumor tissue using various antibodies specific for endothelial cells. CD34 has been the one most commonly used in studies of tumor angiogenesis. Nestin, a class VI intermediate filament protein, was reported to be a good angiogenic marker in animal models. The aim of the current study was to compare the predictive value of angiogenesis as determined by CD34 and nestin on the same group of patients with advanced gastric carcinomas and to evaluate the possibility of nestin being a newer, better angiogenesis marker. Immunohistochemical staining using antinestin polyclonal antibody and anti-CD34 monoclonal antibody was carried out on surgical specimens from 61 patients with advanced gastric adenocarcinomas. The sensitivity of each of the two antibodies was evaluated by microvessel density (MVD) measurement by counting vessels in three 200x fields of intense neovascularization ("hot spots") of invasive tumors using a digital image analyzer. Immunoreactivity for nestin and CD34 was seen in the endothelial cells, and no stain was noted in the negative controls. MVD determined by nestin [87.74 +/- 29.30 (mean +/- standard deviation)] staining was significantly greater than that obtained by CD34 (82.48 +/- 32.27), and the difference was statistically significant. There was no correlation between MVD and patient clinical outcome with either antibody. Interestingly, in patients with larger carcinomas, MVD determined by nestin correlated better with longer survival than CD34. The difference was statistically significant. These results indicate that nestin is the better marker to evaluate neovascularity in endothelial cells. Evaluation of MVD determined by immunohistochemistry has limited value in patients with gastric carcinomas.

Adenocarcinoma↗

PubMedDate not supplied

Endoneurial microangiopathy of sural nerve in experimental vacor-induced diabetes.

The pathogenic mechanism of diabetic peripheral neuropathy is multifactorial. This study investigated microangiopathic changes of endoneurial vessels of sural nerve in Vacor-induced diabetic rats. Experimental rats were divided into 3 groups: acute (80 mg/kg, once), chronic diabetic (8 mg/kg, 14 times), and control. Ultrastructural morphometric parameters of endoneurial microvessels, blood glucose, and body weight changes were statistically analyzed, and correlations among the variables were evaluated. The body weight and blood glucose levels were significantly different between the control and diabetic rats. The blood glucose was more significantly elevated in the acute diabetic rats than the chronic diabetic rats. Inner and outer vascular circumference, vascular area, luminal area, basement membrane area, and basement membrane thickness were significantly increased in the acute diabetic rats compared to the control group, but not between the chronic diabetic rats and the control group. The thickness of basement membrane was positively correlated with hyperglycemia and body weight loss (P < .01). These results suggest that the microangiopathy of the peripheral nerve could be developed in acute Vacor-induced diabetes. The decreased perfusion through microangiopathic endoneurial vessels appears to have a pathogenic role causing diabetic peripheral neuropathy.

Animals↗