Young-Yim Kim

Plasma Matrix Metalloproteinases, Cytokines, and Angiogenic Factors in Moyamoya Disease

Objective To document the expression patterns of various matrixins, cytokines and angiogenic factors in plasma to assess their involvement in the pathogenesis of moyamoya disease (MMD). Methods This study included plasma samples from 20 MMD patients and nine healthy individuals. The plasma concentration of five matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9, MMP-12), monocyte chemoattractant protein-1 (MCP-1), resistin, three interleukins (IL-1β, IL-6, IL-8), tumour necrosis factor-α, vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB) and basic fibroblast growth factor was determined using multianalyte profiling systems. The concentration of the tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2) was measured using ELISA. Gelatin zymography for MMP-2 and MMP-9 was also performed. Results MMD patients exhibited significantly higher plasma concentrations of MMP-9, MCP-1, IL-1β, VEGF and PDGF-BB, and lower plasma concentrations of MMP-3, TIMP-1 and TIMP-2 compared with healthy controls. Significant correlations were found among MMP-9, MCP-1, VEGF, PDGF-BB and TIMP-2 in MMD patients. Conclusion There were distinctive expression patterns of matrixins, cytokines and angiogenic factors in MMD patients, which seemed to correlate with disease pathogenesis. The balance between MMPs and TIMPs was disrupted in MMD and correlated with disease pathogenesis. Increased plasma levels of MCP-1 and VEGF in MMD patients may play a role in the recruitment of vascular progenitor cells and in the formation of collateral vessels.

Gene expression profile analyses of cortical dysplasia by cDNA arrays

Cortical dysplasia (CD) is a well-recognized cause of intractable epilepsy, especially in children and is characterized histologically by derangements in cortical development and organization. The objective of this study was to expand the current knowledge of altered gene expression in CD as a first step towards in the identification of additional genes operative in the evolution of CD. Surgical specimens were obtained from eight patients (4 males and 4 females; age range 2-38 years; mean 15 years) with a pathologic diagnosis of CD. Nondysplastic temporal neocortex was obtained from a 2-year-old boy with intractable epilepsy and medial temporal lobe ganglioglioma. After total RNA isolation from frozen brain tissues, we carried out gene expression profiling using a cDNA expression array. Differences in gene expressions between CD and the nondysplastic neocortex were confirmed by semi-quantitative conventional reverse transcription-PCR. Three genes (recombination activating gene 1 (RAG1), heat shock 60 kDa protein 1 (HSP-60), and transforming growth factor beta1 (TGF beta1)) were found to be up-regulated more than two-fold in CD, whereas four genes (phosphoinositide-3-kinase regulatory subunit polypeptide 1 [p85 alpha] (PI3K), frizzled homolog 2 [Drosophila], Bcl-2/adenovirus E1B 19 kDa interacting protein (NIP3), and glia maturation factor beta (GMF beta)) were down-regulated to less than 50% of their normal levels. Interestingly, the majority of genes showing altered expression were associated with apoptosis. Our study demonstrates diverse changes in gene expression in CD. However, it remains to be shown which of these are causally related to the evolution of CD.

Tissue Expression of Manganese Superoxide Dismutase Is a Candidate Prognostic Marker for Glioblastoma

Background: Characterization of a rare subgroup of glioblastoma patients who survive for more than 3 years (long-term survival glioblastoma, LTSGBL, patients) may be helpful to identify prognostic factors. Materials and Methods: A molecular-profiling proteomic approach using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify prognostic factors associated with glioblastoma by comparing frozen tumor tissue from LTSGBL patients with matched samples from short-term survival glioblastoma (STSGBL) patients. Western blot (WB) analysis, reverse-transcriptase polymerase chain reaction (RT-PCR) and immmunohistochemical (IHC) staining were used for confirmation. Results: Among most candidate spots identified by 2-DE, lack of overexpression of manganese superoxide dismutase (MnSOD) in LTSGBL samples was consistently observed using WB and RT-PCR. Conclusion: These results suggest that MnSOD expression level in tumor tissue is a candidate marker for the prognosis of glioblastoma patients.

Prenatal growth pattern of the human maxilla.

Regarding maxillofacial morphogenesis there has been a long debate on the growth of the maxillary structure. Using 120 normal fetal maxillae of gestational ages from 16 to 41 weeks, palatal radiograms and frontal histologic sections were made. We have observed two pairs of accentuated growth areas in the fetal maxillae and named them primary growth centers to formulate the maxillary trapezoid (MT) by radiologic image. The MT is formed by four primary growth centers that are best demonstrated by palatal radiograms of the fetal maxilla as well as by frontal histologic sections. The dimensional increase in the MT during the fetal period is documented and statistically analyzed. From this series of results, we have suggested that the growth centers which demarcate the MT are the basic structures of the developing human maxilla. It was also found that the four primary growth centers are the most active sites for maxilla formation until 20 weeks of gestation and thereafter the growth of the maxilla is enhanced by the participation of the intramembranous bone formation along the periphery. This was in contrast to the central primary growth centers that have already finished maturation in the early fetal period and remain only as a peripherally radiating arrangement of thick trabecular bones.

Smooth-muscle progenitor cells isolated from patients with moyamoya disease: novel experimental cell model

OBJECT Moyamoya disease (MMD) is a cerebrovascular occlusive disease affecting bilateral internal carotid termini. Smooth-muscle cells are one of the major cell types involved in this disease process. The characteristics of circulating smooth-muscle progenitor cells (SPCs) in MMD are poorly understood. The authors purified SPCs from the peripheral blood of patients with MMD and sought to identify differentially expressed genes (DEGs) in SPCs from these patients. METHODS The authors cultured and isolated SPCs from the peripheral blood of patients with MMD (n = 25) and healthy control volunteers (n = 22). After confirmation of the cellular phenotype, RNA was extracted from the cells and DEGs were identified using a commercially available gene chip. Real-time quantitative reverse transcription polymerase chain reaction was performed to confirm the putative pathogenetic DEGs. RESULTS The SPC-type outgrowth cells in patients with MMD invariably showed a hill-and-valley appearance under microscopic examination, and demonstrated high α-smooth muscle actin, myosin heavy chain, and calponin expression (96.5% ± 2.1%, 42.8% ± 18.6%, and 87.1% ± 8.2%, respectively), and minimal CD31 expression (less than 1%) on fluorescence-activated cell sorter analysis. The SPCs in the MMD group tended to make more irregularly arranged and thickened tubules on the tube formation assay. In the SPCs from patients with MMD, 286 genes (124 upregulated and 162 downregulated) were differentially expressed; they were related to cell adhesion, cell migration, immune response, and vascular development. CONCLUSIONS With adequate culture conditions, SPCs could be established from the peripheral blood of patients with MMD. These cells showed specific DEGs compared with healthy control volunteers. This study provides a novel experimental cell model for further research of MMD.

Three novel mutations of the PKD1 gene in Korean patients with autosomal dominant polycystic kidney disease.

Mutations at the PKD1 locus account for 85% of cases of the common genetic disorder called autosomal dominant polycystic kidney disease (ADPKD). Screening for mutations of the PKD1 gene is complicated by the genomic structure of the 5′‐duplicated region encoding 75% of the gene. To date, more than 90 mutations of the PKD1 gene have been reported in the European and American populations, and relatively little information is available concerning the pattern of mutations present in the Asian populations. We looked for mutations of the PKD1 gene in 51 unrelated Korean ADPKD patients, using polymerase chain reaction (PCR) with primer pairs located in the 3′ single‐copy region of the PKD1 gene and by single‐strand conformation polymorphism (SSCP) analysis. We found three novel mutations, a G to A substitution at nucleotide 11012 (G3601S), a C to A substitution at nucleotide 11312 (Q3701X), and a C to T substitution at nucleotide 12971 (P4254S), and a single polymorphism involving a G to C substitution at nucleotide 11470 (L3753L). These mutations were not found in control individuals, and no other mutations in the 3′ single‐copy region of the PKD1 gene of patients with these mutations were observed. In particular, P4254S segregated with the disease phenotype. The clinical data of affected individuals from this study, and of previously reported Korean PKD1 mutations, showed that patients with frameshift or nonsense mutations were more prone to develop end‐stage renal failure than those with missense mutations. Our findings indicate that many different PKD1 mutations are likely to be responsible for ADPKD in the Korean population, as in the Western population.

Spatial Learning of an Autonomous Mobile Robot Using Model-Based Approach

Abstract A method of recognizing the characteristics of spatial structure for an autonomous mobile robot (AMR) is proposed in this paper. The recognition scheme is based on Bayesian hypothesis reasoning, and uses ultrasonic sensor data obtained from an robot in an unknown environment. The optimal hypothesis reasoning scheme is difficult to implement due to its exponentially increasing number of hypothesis as a function of observation time. The proposed scheme uses only current spatial representative primitives (SRPs) along with their transition probabilities and approximates the optimal scheme. The SRPs are defined as spatial continuous characteristics. The scheme uses all SRPs and the Bayesian reasoning for generation of exploration direction. This is similar to that of human spatial recognition and it improves the performance of a hypothesis reasoning scheme. The performance of the proposed scheme is evaluated by testing an AMR in a building environment.

Planning Optimal Paths in a Partially Unknown Environment

Abstract Path planning for mobile robots has two planning stages, namely global path planning and local path planning. In this paper, the two path plannings employ a network representing its working area by means of nodes and arcs. Paths between all pairs of nodes are determined in global path planning and a revised path from the current position of the mobile robot to a destination is computed in local path planning. In order to reduce the computational burden, an algorithm based on optimal network decomposition is proposed. Our new methodology has been implemented on a mobile robot. The results show that the robot successfully navigates to its destinations along optimal paths in partially unknown environment.