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Biomedical subjects

Young-Joon Lee

Publications and source records attributed to Young-Joon Lee.

14 recordsLinked to original sources

Genetic manipulation of a primary metabolic pathway for L-ornithine production in Escherichia coli.

Metabolic engineering has been used to improve L-ornithine biosynthesis in Escherichia coli W3110. L-Ornithine production increased from 0.3 to 3.2 mg/g (dry cell weight) when the primary L-ornithine biosynthetic pathway was optimized by disrupting the pathway transcription repressor, thereby increasing the expression of the genes involved in the pathway, and by preventing conversion of L-ornithine into citrulline. When a feedback-resistant N-acetylglutamate synthetase gene (argA214) was placed under the control of the arabinose-inducible promoter, either in the chromosome or on a multicopy plasmid in the cell, the combination of overexpression of argA214 with an argF argI argR triple knockout mutation had an additive effect on L-ornithine production but only when exogenous glutamate was present. When speF (which encodes ornithine decarboxylase) and proB (which encodes gamma-glutamyl kinase) were inactivated to prevent the conversion of L-ornithine to putrescine and to block the biosynthesis of a side branch of L-ornithine, respectively, L-ornithine production was further enhanced approx. 140% from 5.5 to 13.2 mg/g (dry cell weight).

Amino-Acid N-Acetyltransferase↗

Myositis ossificans of the abdominal rectus muscle: report of a case.

We herein report a rare case of myositis ossificans originating from the abdominal rectus muscle, found in a 38-year-old woman who presented with a left upper abdominal mass. The mass was initially suspected to be a malignant neoplasm because no history of either operation or trauma existed for this patient. Moreover, the location of the mass was unusual and the enhancement patterns of the dynamic magnetic resonance images were similar to that of a malignant tumor. Based on the radiologic findings, a surgical exploration was performed. A well-circumscribed mass, which measured 3.2 x 2 cm, was found in the rectus muscle. Microscopic findings showed a typical zonal pattern with a fibroblastic central zone and a zone of ossification at the periphery. Although abdominal myositis ossificans is extremely rare, it is one of the causes of abdominal mass lesions and can be mistaken for a malignant tumor. Therefore, a thorough knowledge of the evolution of myositis ossificans is necessary and in cases with malignant suggestion on magnetic resonance imaging, like that seen in our case, we suggest that a surgical excision may be necessary for both the diagnosis and treatment.

Abdominal Neoplasms↗

Malignant peripheral nerve sheath tumor arising from the colon in a newborn: report of a case and review of the literatures.

A malignant peripheral nerve sheath tumor (MPNST) is a rare neoplasm arising from peripheral nerve sheath. Here, we report the first case of MPNST arising in the colon and also the youngest case of MPNST in the gastrointestinal tract. The patient was a 2-day-old neonate with symptoms and signs of intestinal obstruction. The patient had no family history or stigmata of neurofibromatosis type 1. A computed tomographic scan revealed a 5-cm-sized mass in ascending colon causing intestinal obstruction, and emergent right hemicolectomy was performed. The microscopic examination showed atypical spindle cells with hyperchromatic nuclei and high mitotic activity. The results of immunohistochemical staining, which showed positivity for S-100 and vimentin as well as negativity for smooth muscle actin, CD34, and c-Kit, supported the final diagnosis of MPNST. Genetic analysis of the patient revealed no abnormalities. After surgery, the patient recovered uneventfully and has been free of the disease for 17 months.

Colon↗

Periciliary Y-V epicanthoplasty.

The epicanthal fold is a semilunar flap of eyelid skin on the medial aspect of the eye. Many surgical techniques have been described to eliminate the epicanthal fold, which is a feature uniquely predominant among the Asian population. However, many surgeons avoid epicanthoplasty because of the fear of visible scar formation. From January of 2002 to April of 2004, 118 patients with medial epicanthal folds underwent epicanthoplasty using a periciliary Y-V advancement procedure for the prevention of visible scar formation. The mean age of the patients was 25.2 years (range, 16 years to 56 years). The median follow-up period was 6 months (range, 2 weeks to 2 years). We performed periciliary Y-V epicanthoplasty only when a patient had wide interepicanthal distance (over 32 mm) or a completely eclipsed lacrimal caruncle. Most of the patients attained satisfactory results, and there were few complications in our cases. Scarring of the medial canthal area has not been a problem with this technique because we designed incisions along the eyelashes and skin-mucosal junctions. We have found that our periciliary Y-V epicanthoplasty is a very reliable and effective method for eliminating the epicanthal fold with minimal scar formation.

Adolescent↗

Intra-abdominal angiosarcoma developing in a capsule of a foreign body: report of a case with associated hemorrhagic diathesis.

BACKGROUND: Angiosarcoma occurs very rarely in the gastrointestinal tract and can present great diagnostic difficulty, especially when it is associated with intraabdominal abscess or granulation tissue. CASE PRESENTATION: We report a case where the angiosarcoma was diagnosed after the occurrence of disseminated angiosarcoma and concurrent hemoperitoneum. The tumor developed in the fibrous capsule of a foreign body, which was possibly related to the previous appendectomy twenty years ago, and became a widely disseminated malignant neoplasm in the abdomen. After the operation, the patient's course was dominated by a fatal consumptive coagulapathy. Pathologic examination of the multiple intra-abdominal lesions showed the histological and immunohistological characteristics of the angiosarcoma. CONCLUSION: Even though angiosarcoma in the gastrointestinal tract is extremely rare, when dealing with intraabdominal abscess or the gastrointestinal bleeding in patients who have undergone surgery or radiation therapy in the past, the possibility of angiosarcoma should be considered. To make the definite diagnosis of angiosarcoma and to avoid the misdiagnosis of foreign body granuloma, thorough histological examination and immunohistochemical staining may be prerequisite.

Journal Article↗

The kringle domain of tissue-type plasminogen activator inhibits in vivo tumor growth.

The two-kringle domain of tissue-type plasminogen activator (t-PA) has previously been shown to contain anti-angiogenesis activity. In this study, we explored the potential in vivo anti-tumor effects of the recombinant kringle domain (TK1-2) of human t-PA. Anti-tumor effects of purified Pichia-driven TK1-2 were examined in nude mice models by subcutaneous implantation of human lung (A-549) and colon (DLD-1, HCT-116) cancer cell lines. Mice bearing the tumors were injected with PBS or purified TK1-2 (30 mg/kg) i.p. every day for 22 days. TK1-2 treatment suppressed the A-549, DLD-1, and HCT-116 tumor growth by 85.3%, 52.4%, and 62.5%, respectively. Immunohistological examination of the tumor tissues showed that TK1-2 treatment decreased the vessel density and also the expression of angiogenesis-related factors including angiogenin, VEGF, alpha-SMA, vWF, and TNF-alpha, and increased the apoptotic fraction of cells. TK1-2 neither inhibited in vitro growth of these cancer cells nor affected t-PA-mediated fibrin clot lysis. These results suggest that TK1-2 inhibits the tumor growth by suppression of angiogenesis without interfering with fibrinolysis.

Angiogenic Proteins↗

The value of intraoperative imprint cytology in the assessment of lymph node status in gastric cancer surgery.

BACKGROUND: The intraoperative assessment of lymph node status is important when performing limited surgery in gastric cancer patients. Currently available techniques for this assessment are frozen section, imprint cytology, and other molecular methods; most current studies use the frozen-section method. In the present study, we focused on the accuracy and feasibility of imprint cytology as a tool to assess lymph node status intraoperatively in gastric cancer surgery. METHODS: Between April 2001 and March 2003, we performed imprint cytology of the sentinel nodes in 260 consecutive patients. After review by an experienced cytopathologist, the sensitivity, specificity, and overall accuracy of the method were determined. RESULTS: The time required for the intraoperative imprint cytology was 8 min, and the sensitivity, specificity, and overall accuracy were 52.2%, 88.8%, and 73.8%, respectively. CONCLUSION: Imprint cytology could be a useful technique for the assessment of lymph node status intraoperatively if the sensitivity and specificity can be improved to an acceptable level.

Feasibility Studies↗

Nonincisional blepharoplasty using the debulking method.

As more women work outside home, a growing number of women who want to have a natural-looking double eyelid choose the method with a short healing time and less pain. Thus blepharoplasty by the nonincisional method is performed frequently. This technique uses 7-0 nylon for simple triple ring-shaped or center doubled triple ring-shaped suture, with removal of subcutaneous fat, pretarsal muscle, and orbital septum through small incisions. This prevents the possibility that the folds will be loosened. By creation of a scar adhesion between the wider portion of the dermis and the tarsal plate after debulking of the soft tissue, the nonincisional method can be applied to a very thin eyelid without any difficulty.A retrospective review of the data for 327 patients who underwent nonincisional blepharoplasty using the debulking method from November 24, 2000 through March 9, 2003 is presented. Except for four cases, the procedures were successful. Two complications of conjunctivitis occurred, requiring removal of the buried suture, and two patients reported a mild scar.

Adipose Tissue↗

Comparison of plasma D-dimer and thrombus precursor protein in patients with operable breast cancer as a potential predictor of lymph node metastasis.

Fibrin formation and removal is continuous during the development of malignancy. Plasma D-dimer is indicative of ongoing fibrinolysis, and circulating soluble fibrin polymer [thrombus precursor protein (TpP)] represents thrombogenic activity. We evaluated the relationship between plasma D-dimer and TpP levels with tumor extent and examined the use of these markers as possible predictors of lymph node metastasis in breast cancer. Preoperative plasma levels of D-dimer and TpP were measured in these 120 patients (93 breast cancer, 27 benign breast disease) and 29 healthy controls. Plasma levels of D-dimer in patients with breast cancer were significantly higher than in healthy controls and in those with benign breast disease. Plasma D-dimer levels in patients with breast cancer were found to be significantly increased according to tumor stage. We also observed that plasma levels of D-dimer were higher in patients with lymph node metastasis than in patients without metastasis. In contrast, TpP levels were not significantly different by the tumor stages and lymph node metastasis. In conclusion, increased D-dimer levels in breast cancer may suggest that an ongoing fibrinolysis within breast cancer tissue occurs during tumor progression. Positive D-dimer levels might be useful for identifying metastatic lymph node in patients with operable breast cancer. However, plasma TpP was not found to be a sensitive marker for detecting tumor-associated subclinical coagulopathy.

Adult↗

Integrin alphaIIbbeta3-specific synthetic human monoclonal antibodies and HCDR3 peptides that potently inhibit platelet aggregation.

The interaction of fibrinogen with integrin alphaIIbbeta3 (GPIIb/IIIa), in part mediated by an RGD tripeptide motif, is an essential step in platelet aggregation. Based on their inhibition of platelet aggregation, three integrin alphaIIbbeta3 inhibitors are clinically approved. The clinically most widely used integrin alphaIIbbeta3 inhibitor abciximab is a chimeric mouse/human antibody that induces thrombocytopenia, often severe, in 1-2% of patients due to a human anti-mouse antibody (HAMA) response. In addition, unlike other ligands mimicking small molecular drugs, abciximab cross-reacts with integrin alphavbeta3 and alphaMbeta2. Here we used phage display to select monoclonal antibodies specific to integrin alphaIIbbeta3 from a synthetic human antibody library based on the randomized HCDR3 sequence VGXXXRADXXXYAMDV. The selected antibodies revealed a strong consensus in HCDR3 (V(V/W)CRAD(K/R)RC) and high specificity toward integrin alphaIIbbeta3 but not to other RGD binding integrins such as alphavbeta3, alphavbeta5, and alpha5beta1. The selected antibodies as well as three synthetic peptides (VWCRADRRC, VWCRADKRC, and VVCRADRRC) whose sequences were derived from the HCDR3 sequences of the selected antibodies strongly inhibited the interaction between integrin alphaIIbbeta3 and fibrinogen and platelet aggregation ex vivo. To our knowledge, these are the first fully human monoclonal antibodies that are specific to integrin alphaIIbbeta3 and can potently inhibit platelet aggregation.

Amino Acid Motifs↗

Circulating numbers of endothelial progenitor cells in patients with gastric and breast cancer.

Angiogenic factors like VEGF or G-CSF were reported to mobilize endothelial progenitor cells (EPCs) from the bone marrow. These EPCs were shown to be incorporated in the neovessels of developing tumors. Although the concentrations of angiogenic factors in the peripheral blood were reported to be elevated in cancer patients, the number of circulating EPCs has not been previously investigated. In this study, the number of EPCs circulating in the blood in 16 healthy controls and 71 newly diagnosed cancer patients was examined by a culture assay of peripheral blood mononuclear cells. The number of circulating EPCs was not found to be increased in cancer patients, although the plasma levels of VEGF were elevated. It is suggested that VEGF, at concentrations typical of those observed in the blood of cancer patients, does not mobilize EPCs into the peripheral blood.

Breast Neoplasms↗

Meniscal tear configurations: categorization with MR imaging.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of MR imaging for categorizing the configuration of meniscal tears of the knee. MATERIALS AND METHODS: Fast spin-echo MR images obtained at 1.5 T from 110 patients who had meniscal tears identified at arthroscopy were retrospectively and independently classified by two reviewers into five configurations: horizontal, longitudinal, radial, oblique, and complex. MR imaging categorization was compared with arthroscopic results as the standard of reference. Data were also analyzed with longitudinal and oblique tears combined because these usually are reparable, and with horizontal, radial, and complex tears combined because these usually are not reparable. Interobserver and intraobserver agreements were calculated using kappa coefficients. RESULTS: At arthroscopy, meniscal tears were categorized as horizontal (n = 44), longitudinal (n = 34), complex (n = 22), radial (n = 11), and oblique (n = 5). Sensitivity, specificity, and accuracy of each reviewer for the reparable tears were 82%, 92%, and 89%; and 59%, 97%, and 84%, respectively. Interobserver agreements were fair between reviewer 1 and the first and second interpretations of reviewer 2 (kappa = 0.25, p < 0.005; and kappa = 0.21, p < 0.05, respectively). Intraobserver agreement was substantial (kappa = 0.71, p < 0.001). CONCLUSION: MR imaging was accurate for predicting reparable meniscal tears and was sensitive for the determination of nonreparable tears.

Adolescent↗

Proteome analysis of human liver tumor tissue by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-mass spectrometry for identification of disease-related proteins.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide and is a leading cause of death. To contribute to the development and improvement of molecular markers for diagnostics and prognostics and of therapeutic targets for the disease, we have largely expanded the currently available human liver tissue maps and studied the differential expression of proteins in normal and cancer tissues. Reference two-dimensional electrophoresis (2-DE) maps of human liver tumor tissue include labeled 2-DE images for total homogenate and soluble fraction separated on pH 3-10 gels, and also images for soluble fraction separated on pH 4-7 and pH 6-9 gels for a more detailed map. Proteins were separated in the first dimension by isoelectric focusing on immobilized pH gradient (IPG) strips, and by 7.5-17.5% gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels in the second dimension. Protein identification was done by peptide mass fingerprinting with delayed extraction-matrix assisted laser desorption/ionization-time of flight-mass spectrometry (DE-MALDI-TOF-MS). In total, 212 protein spots (117 spots in pH 4-7 map and 95 spots in pH 6-9) corresponding to 127 different polypeptide chains were identified. In the next step, we analyzed the differential protein expression of liver tumor samples, to find out candidates for liver cancer-associated proteins. Matched pairs of tissues from 11 liver cancer patients were analyzed for their 2-DE profiles. Protein expression was comparatively analyzed by use of image analysis software. Proteins whose expression levels were different by more than three-fold in at least 30% (four) of the patients were further analyzed. Numbers of protein spots overexpressed or underexpressed in tumor tissues as compared with nontumorous regions were 9 and 28, respectively. Among these 37 spots, 1 overexpressed and 15 underexpressed spots, corresponding to 11 proteins, were identified. The physiological significance of the differential expressions is discussed.

Carcinoma, Hepatocellular↗

RFLP haplotypes of beta-globin gene complex of beta-thalassemic chromosomes in Koreans.

Korea is in the low-prevalence area of beta-thalassemia and the Korean population has relatively homogenous racial characteristics. Recently, we identified some causative mutations of the Korean beta-thalassemia patients. In order to elucidate the genetic background of beta-thalassemia alleles in Koreans, we determined the restriction fragment length polymorphism (RFLP)-haplotype and framework (FW) in nine beta-thalassemia chromosomes of five different causative mutations by PCR-based method and family linkage study. The result that the haplotype and the framework linked to the initiation codon ATG-->AGG mutation were -+-++-+ and FW3A, respectively, in all of three families in this study suggests a common origin of this mutation at least in Koreans. A novel beta-thalassemia mutation, codons 89/90 -TG, showed discrepancy between -++--++- and FW1, which could be explained by gene conversion. A case of codons 8/9 +G frameshift mutation had +----++ and FW1. The linkage of the two beta-thalassemia mutations, codon 17 AAG-->TAG and codons 41/42 -TTCT, with specific haplotypes and frameworks common to the Koreans and the neighboring countries suggests that those mutations are influenced by the genetic flow from the south China.

China↗