Moon-Whan Im

Maternal and fetal exposure to bisphenol A in Korea

Bisphenol A (BPA) is a well-known endocrine disrupter used widely. Despite the potential risk of human exposure to BPA, little information exists concerning maternal and fetal exposure to BPA during pregnancy in Korea. This study purposed to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels to BPA in Korean pregnant women and their fetuses. Maternal blood and umbilical cord blood were collected from 300 subjects, and total BPA levels were measured. Blood BPA concentrations ranged from non-detectable to 66.48 microg/L in pregnant women and from non-detectable to 8.86 microg/L in umbilical cords. Serum BPA levels in most pregnant women were higher than in corresponding fetal umbilical cords and a positive correlation was found between in maternal and fetal BPA concentrations (p<0.05).

Multipotency and growth characteristic of periosteum-derived progenitor cells for chondrogenic, osteogenic, and adipogenic differentiation

The mesengenic multipotency of cryopreserved periosteum-derived progenitor cells (PDPCs) for chondrogenesis, osteogenesis and adipogenesis was investigated. Differentiation was verified using RT-PCR and histological analysis. For characterization, FACS analysis was performed with specific surface markers of mesenchymal stem cells (MSCs). Among PDPCs, unsorted periosteum-derived cells (PDCs) and dermal fibroblasts, the most distinct characteristics were found to be CD9, CD105, and CD166. In addition, these markers in PDPCs were continuously maintained until passage 15. We developed a rapid method for the isolation of PDPCs that can differentiate into mesodermal lineages and provide enough cells in a short period of time for allogeneic cell therapy.

Maternal exposure to environmental tobacco smoke, GSTM1/T1 polymorphisms and oxidative stress

Environmental tobacco smoking (ETS) is known to be associated with adverse pregnancy outcomes. The purpose of this study was to investigate the relationship between maternal exposure to ETS and oxidative stress for neonates, as well as the effect of maternal genetic polymorphisms, glutathione-S-transferase M1 (GSTM1) and GSTT1, on this relationship. We used the radioimmunoassay to measure the urinary concentration of cotinine in 266 pregnant women who denied smoking cigarettes during pregnancy and in their singleton babies. In addition, the urinary concentration of malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) were assessed using high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. We also extracted DNA from whole blood obtained from the mothers and then conducted polymerase chain reaction on the samples to determine the GSTM1 and GSTT1 genotypes. The maternal cotinine concentration was found to be significantly associated with the fetal cotinine concentration, particularly for mothers whose urine cotinine concentrations were above 120 microg/gcr (p<0.01). The fetal urine cotinine concentration was also found to be significantly associated with the fetal urine MDA concentration (p<0.01). When the null type maternal GSTM1 or the wild type GSTT1 was present, the maternal oxidative stress level increased significantly as the maternal continine concentration increased (MDA: p<0.01; 8-OH-dG: p<0.01). No significant relationships were found between maternal cotinine and fetal oxidative stress markers, however, the fetal MDA levels increased significantly as fetal cotinine levels increased. These results suggest that the maternal exposure to ETS affects the fetal urine cotinine concentration and induces production of maternal oxidative stress. In addition, maternal genetic polymorphisms of GSTM1 and GSTT1 may modify the oxidative stress by maternal exposure to ETS.

Chondrogenic differentiation of human umbilical cord blood-derived multilineage progenitor cells in atelocollagen

BACKGROUND For successful stem cell-based therapy, not only are alternative good cell sources needed but appropriate scaffolds are key factors. The main purpose of this study was to evaluate the multipotentiality of multilineage progenitor cells (MLPC) and assess the three-dimensional cultivation and chondrogenic differentiation of MLPC in atelocollagen gel for application of tissue-engineered cartilage constructs. METHODS MLPC, human umbilical cord blood-derived clonal cell lines, from BioE Inc. were used. Immunophenotypes of MLPC were characterized using a fluorescence-activated cell sorter (FACS). In vitro differentiation potentials into osteogenic, adipogenic and chondrogenic lineages were examined. Differentiated cells were characterized by reverse transcriptase-polymerase chain reaction (RT-PCR), histologic and immunofluorescence staining. RESULTS Clonogenic MLPC maintained immunophenotypes with specific surface markers of mesenchymal stromal cells (MSC). The osteogenic and adipogenic potentials of MLPC were demonstrated by quantitative real-time PCR, alkaline phosphates activity and Oil Red O staining. Furthermore, MLPC were successfully differentiated into chondrocytes in atelocollagen gel, which was confirmed by RT-PCR and immunofluorescence staining for type II collagen protein. DISCUSSION Whenever MSC are considered for the treatment of cartilage defects, a variety of scaffolds have been utilized as successful carriers for cell delivery. Our results suggest that MLPC can serve as an alternative source for stem cell-based therapy and transplantation. The chondrogenic potential of MLPC in atelocollagen could be suitable for cartilage tissue engineering.

Mucinous adenocarcinoma arising from one retroperitoneal mature cystic teratoma in a postmenopausal woman.

Malignant degeneration of a retroperitoneal mature cystic teratoma to adenocarcinoma at postmenopausal age is extremely rare. A 72‐year‐old woman with mucinous adenocarcinoma arising from a retroperitoneal mature cystic teratoma is presented.

Xenoreactivity of human clonal mesenchymal stem cells in a major histocompatibility complex-matched allogeneic graft-versus-host disease mouse model.

Effects of mesenchymal stem cells (MSCs) on graft-versus-host disease (GVHD) have been actively investigated since the discovery of the immunomodulation property of MSCs about a decade ago. Human clonal MSCs (hcMSCs) were isolated from human bone marrow aspirate according to our newly established isolation protocol called subfractionation culturing method, and were evaluated for their efficacy on GVHD treatment, using a mouse MHC-matched B6-->BALB.B GVHD model system. Although the hcMSCs can suppress the allogeneic proliferation of human peripheral blood mononuclear cells in in vitro, the administration of the hcMSCs failed to reduce the GVHD-related mortality of the murine recipients. One of the reasons might be that murine cytokines such as IFN-gamma and TNF-alpha cannot activate the hcMSCs. Based on these results, we suggest that xenogeneic MSCs may not be used for the treatment of GVHD.

Combined Treatment of an Intratumoral Injection of Dendritic Cells and Systemic Chemotherapy (Paclitaxel) for Murine Fibrosarcoma

A novel combined treatment of conventional chemotherapy with an intratumoral injection of syngeneic dendritic cells (DCs) has emerged as a potent cancer treatment strategy. In this study, we evaluated the synergistic effect of an intraperitoneal (i.p.) injection of a chemotherapeutic drug, paclitaxel, and an intratumoral (i.t.) injection of syngeneic bone marrow-derived DCs for the treatment of pre-existing fibrosarcoma. Subcutaneous tumors were established using MCA102 fibrosarcoma cells in syngeneic C57BL/6 mice. The results demonstrated that the combined treatment of paclitaxel chemotherapy and the injection of DCs led to complete tumor regression, in contrast to only partial eradication of the tumors with chemotherapy or DCs alone. Furthermore, the tumor-free mice were able to resist a repeat challenge with the same type of tumor. These findings suggest that a combination therapy of systemic chemotherapy along with the intratumoral administration of DCs is a potent treatment strategy for fibrosarcoma.

Associations between enhanced fetal hemoglobin levels and ineffective reticulocyte production in diabetics.

Data for immature reticulocyte production in relation to elevated HbF fraction in diabetics are limited. The present study investigated whether enhanced HbF synthesis has any associations with reticulocytopoiesis and reticulocyte maturity in patients with diabetes. A total of 379 adult diabetic patients (192 males, 187 females; age = 37–79 years) were investigated. Patients were evaluated by several measurements: fetal-type erythropoiesis (HbF), reticulocytopoiesis (reticulocytes and their subpopulations), glycemic controls [glycated hemoglobin (HbA1c) and ketone in urine], inflammatory parameters [high-sensitivity C-reactive protein (hsCRP)], and iron parameters [serum iron and transferrin saturation (TS)]. Age-matched nondiabetic healthy subjects (n = 156; age = 37–78 years) were chosen as a control group, who had plasma glucose levels ! 100 mg/dl and HbA1c concentrations ! 6.0%. Because age may have some influence on HbF levels, careful attention was paid to match the controls and patients for age. All subject populations were composed of Koreans. None of the subjects had a history of present pregnancy, acute blood loss, nephropathy, or drug abuse, as these are conditions that might affect the production of HbF. HbF and HbA1c were determined by high-pressure liquid chromatography with EDTA-anticoagulated blood using a G7 Glycohemoglobin Analyzer (Tosoh BiosciFetal hemoglobin (HbF) is mainly produced in fetal life and rapidly declines to extremely low levels by the age of 1 year. In healthy adults, HbF levels are usually below 1.0% of total hemoglobin [1] . However, fetal-type erythropoiesis, that is the reemergence of HbF synthesis, may occur in certain inherited or acquired conditions, such as hemoglobinopathies and myelodysplastic syndrome [2] . Erythropoietic stress, as seen in acute blood loss, acute hemolysis, and malignancies affecting the erythropoietic system, is associated with increased HbF production [3] . A relationship between HbF levels and hypoxia has also been reported: increased HbF levels are observed in intrauterine hypoxia, maternal smoking, postnatal hypoxemia from congenital heart disease, and anemia of prematurity [4] . Previous studies have demonstrated that HbF production is significantly enhanced in patients with diabetes [5, 6] . The reason for the increased HbF fraction in diabetics remains unclear. A wide heterogeneity of the results was reported concerning the reappearance of fetal-type erythropoiesis in diabetics. Several investigators suggested that increased prevalence of elevated HbF may be associated with poor glycemic control [7, 8] . On the other hand, another group of researchers reported that no significant differences were observed in glycemic control and the duration of diabetes between patients with high or low HbF levels [9] . Received: July 6, 2009 Accepted after revision: August 18, 2009 Published online: October 30, 2009

Pelvic inflammatory disease with Tc-99m Ciprofloxacin imaging

The clinical diagnosis of pelvic inflammatory disease (PID) is inexact. There are multiple potential symptoms and signs ascribable to PID as predicted by areas of inflammatory involvement. No symptoms or signs are pathognomonic for PID. The authors describe single photon emission computed tomography (SPECT) images of technetium‐99m (99mTc) ciprofloxacin imaging of patients with PID that showed foci of significantly increased uptake in the regions corresponding to the areas of clinical symptoms. We report two such cases of PID. We undertook physical exams, complete blood count, erythrocyte sedimentation rate, C‐reactive protein, Gram stains, wet smears, cultures, Mycoplasma genetic studies, Chlamydia cultures, and SPECT before treatment. During treatment we took laparoscopies, hysteroscopies, biopsies, and cultures. After the treatment, we repeated the same exams. 99mTc ciprofloxacin imaging is considered valuable in persons with symptoms of PID in whom diagnosis is difficult.