This study examined ways of promoting research in the medical sciences by evaluating trends in research funding, and the present status of research funding by the Korea Science and Engineering Foundation (KOSEF). This study analyzed statistics from KOSEF from 1978 to 2003 to examine support for research. In medical science field, group-based programs receive more funding than do individual-based programs. The proportion of research funds allocated to the medical sciences has increased markedly each year. Researchers in the medical sciences have submitted more articles to Science Citation Index (SCI) journals than to non-SCI journals, relative to other fields. Researchers supported by the Mission-Oriented Basic Grants program have published the majority of these papers, followed by those supported by the Programs for Leading Scientists, Regional Scientists, Leading Women Scientists, Young Scientists, and Promising Women Scientists, in that order. Funding by KOSEF reflects many decades of government support for research and development, the development and maintenance of necessary infrastructure, and the education and training of medical scientists.
Biomedical Research/*economics ; Foundations/*economics/statistics & numerical data ; Humans ; Korea ; Research Support/*economics/trends ; Research Support, Non-U.S. Gov't ; Science

Missing data such as appropriateness ratings in clinical research are a common problem and this often yields a biased result. This paper aims to introduce the multiple imputation method to handle missing data in clinical research and to suggest that the multiple imputation technique can give more accurate estimates than those of a complete-case analysis. The idea of multiple imputation is that each missing value is replaced with more than one plausible value. The appropriateness method was developed as a pragmatic solution to problem of trying to assess "appropriate" surgical and medical procedures for patients. Cataract surgery was selected as one of four procedures that were evaluated as a part of the Clinical Appropriateness Initiative. We created mild to high missing rates of 10%, 30% and 50% and compared the performance of logistic regression in cataract surgery. We treated the coefficients in the original data as true parameters and compared them with the other results. In the mild missing rate (10%), the deviation from the true coefficients was quite small and ignorable. After removing the missing data, the complete-case analysis did not reveal any serious bias. However, as the missing rate increased, the bias was not ignorable and it distorted the result. This simulation study suggests that a multiple imputation technique can give more accurate estimates than those of a complete-case analysis, especially for moderate to high missing rates (30 - 50%). In addition, the multiple imputation technique yields better accuracy than a single imputation technique. Therefore, multiple imputation is useful and efficient for a situation in clinical research where there is large amounts of missing data.
Cataract Extraction/*methods ; Humans ; Logistic Models ; Research Support, Non-U.S. Gov't

No abstract available.
Animals ; Humans ; *Organ Transplantation ; Research Support, Non-U.S. Gov't ; T-Lymphocytes/*immunology ; *Transplantation Immunology

Loss of heterozygosity (LOH) has been established as an important genetic mechanism giving rise to malignant neoplasia. The mechanism of LOH has been shown to cause basal cell carcinoma and malignant melanoma as well as other types of skin cancer. A few studies on LOH in sporadic keratoacanthomas have been reported. The purpose of this study was to investigate the significance of LOH in the pathogenesis of sporadic keratoacanthomas developed in 10 Korean patients. The presents of LOH at 7 microsatellite markers (D2S286, D3S1317, D5S346, D9S160, D9S171, D10S185, and D17S261) were evaluated in sporadic keratoacanthomas. LOH was found in only 1 of 10 cases at D10S185. The low frequency of LOH detected in this study suggests that LOH may not be significant in the induction of sporadic keratoacanthomas.
Adult ; Aged ; Female ; Humans ; Keratoacanthoma/*genetics ; *Loss of Heterozygosity ; Male ; Middle Aged ; Research Support, Non-U.S. Gov't

It is not yet clear whether Glutathione S-transferase M1 (GSTM1) polymorphisms affect the risk of breast cancer. The aim of this study is to provide a comprehensive meta-analysis of all the available, published case-control studies on the extent of the possible association between GSTM1 polymorphisms and susceptibility to breast cancer. Twenty case-control studies on GSTM1 and breast cancer were identified using both PUBMED and a manual search. Meta-analysis was conducted by the Peto method. Subgroup analyses were undertaken, in order to explore the relationship between effect sizes and the study characteristics. The overall odds ratio (OR) was found to be 1.06 (95% CI, 0.99-1.14). The OR for post-menopausal women with GSTM1 deficiency was determined to be 1.19 (95% CI, 1.05-1.34). In populations with a low frequency of GSTM1 deficiency, a greater increase was observed (OR, 1.20; 95% CI, 1.08-1.34). Furthermore, the highest associations were found in post-menopausal women with a low frequency of GSTM1 deficiency (OR, 1.44; 95% CI, 1.20-1.73). The fact that GSTM1 deficiency is not rare in the general population implies that the attributable risk for breast cancer could be sizable. Further studies focusing on the structure of haplotype blocks of GSTM1 are required in order to find a specific haplotype with a predisposing breast cancer susceptibility allele.
Breast Neoplasms/*epidemiology/*genetics ; Female ; Glutathione Transferase/*genetics ; Humans ; *Polymorphism, Genetic ; Research Support, Non-U.S. Gov't ; Risk Factors

In association with microtubules, a variety of kinesins play important roles in cellular functions such as intracellular transport of organelles or vesicles, signal transduction, and cell division. In a previous study we revealed that human kinesin superfamily protein member 4 (KIF4) is a chromokinesin that binds to chromosomes. Since localization of several kinds of kinesin at midzone called central spindle, or midbody that connects two daughter cells, or both, suggests their implication in cell division, we investigated KIF4 localization of during mitosis and cytokinesis in Hela cells. In addition to association with segregating chromosomes through entire mitosis, it also localized to the midzone and to midbody at ana/telophase through cytokinesis. Especially in cells at cytokinesis, KIF4 appeared as a doublet facing each other at the apical ends of two daughter cells. Three- dimensional analysis of architectural relationship between microtubule bundles and KIF4 indicated that KIF4 forms a ring structure wrapping around the microtubule bundles. These results suggest that KIF4 is involved in cytokinesis, although direct evidence was not provided in this study.
Animals ; Cell Division/*physiology ; Hela Cells ; Humans ; Immunohistochemistry ; Kinesin/*metabolism ; Mitotic Spindle Apparatus/*metabolism ; Research Support, Non-U.S. Gov't

Neutrophils are important effector cells against protozoan extracellular parasite Entamoeba histolytica, which causes amoebic colitis and liver abscess in human beings. Apoptotic cell death of neutrophils is an important event in the resolution of inflammation and parasite's survival in vivo. This study was undertaken to investigate the ultrastructural aspects of apoptotic cells during neutrophil death triggered by Entamoeba histolytica. Isolated human neutrophils from the peripheral blood were incubated with or without live trophozoites of E. histolytica and examined by transmission electron microscopy (TEM). Neutrophils incubated with E. histolytica were observed to show apoptotic characteristics, such as compaction of the nuclear chromatin and swelling of the nuclear envelop. In contrast, neutrophils incubated in the absence of the amoeba had many protrusions of irregular cell surfaces and heterogenous nuclear chromatin. Therefore, it is suggested that Entamoeba-induced neutrophil apoptosis contribute to prevent unwanted tissue inflammation and damage in the amoeba-invaded lesions in vivo.
Animals ; Apoptosis/*physiology ; Entamoeba histolytica/*physiology ; Host-Parasite Relations/physiology ; Humans ; In Vitro ; Neutrophils/physiology/*ultrastructure ; Research Support, Non-U.S. Gov't

Tissue engineering has the potential to provide cartilaginous constructs capable of restoring the normal function of native articular cartilage following joint injury or degradation. One approach to functional tissue engineering of cartilage involves the in vitro cultivation of tissue constructs by using: (i) chondrogenic cells that can be selected, expanded, and transfected to overexpress the genes of interest, (ii) scaffolds that provide a defined three-dimensional structure for tissue development and biodegrade at a controlled rate. Understanding the functional potential of the cells and the signaling mechanisms underlying their differentiation should lead to innovative protocols for clinical orthopaedic interventions. A large number of growth factors and hormones have been implicated in the regulation of chondrocyte biology, relatively little is known about the intracellular signaling pathways involved. We have tried to define the roles of specific TGF-betadependent signaling pathways involved in the regulation of chondrogenesis from human mesenchymal stem cells. Chondrogenesis induced by TGF-beta in alginate bead system was confirmed by examining cartilage specific type II collagen expression and aggrecan, whereas type I collagen expression was not affected by TGF-beta. Type II collagen mRNA expression was expressed strongly during chondrogenesis and MEK inhibition (U0126) resulted in complete down-regulation of type II collagen. In contrast, aggrecan expression was detected in same level by treatment of U0126. These results strongly suggest that the ERK signaling cascade is involved in TGF-beta induced-chondrogenesis signaling pathways and a role of its pathway is necessary over a longer period to promote type II collagen expression. However, their end product properties in vivo have not been well known. In this study, an articular cartilage from chondrogenic MSCs with PLGA scaffolds (75:25 and 65:35) were made and analyzed its biochemical, histological and mechanical properties in vitro and in vivo. And also, we evaluated the cartilage formation in vivo through the injection of cell-thermosensitive gel complex, a newly developed injectable material. At 12 weeks after PLGA scaffolds containing chondrogenic MSCs transplantation, the separated rabbit distal femur showed a good gross articular cartilage appearance in the transplanted site. In indentation test, compare to the native articular cartilage, the engineered cartilage from two types of (75:25 and 65:35) achieved up to 30-60% in mechanical stiffness. And also, a new model for cartilage formation in bladder, at 14 weeks after injection, we could find out mass formation in the submucosal area grossly. H&E staining, alcian blue staining and other special staining confirmed the chondrogenic differentiation in the mass. These cell therapy technologies can provide the possibility of clinical applications for vesicoureteral reflux and reflux esophagitis, and urinary incontinence as well as articular cartilage regeneration.
Animals ; Cell Differentiation ; Chondrocytes/*cytology ; Humans ; Mesenchymal Stem Cells/*cytology ; Research Support, Non-U.S. Gov't ; *Tissue Engineering

Maintenance of healthy endothelium is essential to vascular homeostasis, and preservation of endothelial cell function is critical for transplant allograft function. Damage of microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection and chronic allograft nephropathy, which is an important predictor of graft loss and is often associated with transplant vasculopathy. In this review, we will discuss the role of microvascular endothelium, in renal allograft dysfunction, particularly as it relates to markers of endothelial dysfunction and endothelial repair mechanisms. We also discuss the potential for therapies targeting endothelial dysfunction and transplant graft vasculopathy.
Humans ; Kidney/*blood supply ; *Kidney Transplantation ; Research Support, Non-U.S. Gov't ; Transplantation, Homologous ; Vascular Diseases/*prevention & control/*therapy

Oxidative stress defined as outbalanced generation of reactive oxygen species (ROS) than the existing antioxidative defense mechanisms plays an important role in tissue injury. Ischemia/reperfusion accompanied during organ transplantation is well- established oxidative stress-induced tissue injury. We hypothesized that oxidative stress may also play a role in the development and progression of chronic allograft nephropathy (CAN), since that ROS are major signaling molecules of growth factors and cytokines [platelet-derived growth factors, transforming growth factor-beta1 (TGF-beta1) ] upregulated in the kidney of CAN, that ROS in turn upregulate TGF-beta1, and that mycophenolic acid may inhibit features of CAN [proliferation and extracellular matrix (ECM) accumulation in vascular smooth muscle cells and glomerular mesangial cells] through inhibiting cellular ROS. Cellular ROS activate signal transduction cascade (protein kinase C, mitogen-activated protein kinases, and janus kinases) and transcription factors (nuclear factor-kappa B, activated protein-1, specificity protein 1, and signal transducers and activators of transcription) leading to regulation of genes and proteins involved in cellular proliferation, ECM remodeling, and apoptosis accompanied in CAN. This review is intended to provide an overview of oxidative stress in renal allograft nephropathy.
Chronic Disease ; Humans ; Kidney Diseases/*etiology ; Kidney Transplantation/*adverse effects ; *Oxidative Stress ; Research Support, Non-U.S. Gov't