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.

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 ((99m)Tc) 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. (99m)Tc ciprofloxacin imaging is considered valuable in persons with symptoms of PID in whom diagnosis is difficult.

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.

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.

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.

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.

Placental superoxide dismutase, genetic polymorphism, and neonatal birth weight.

BACKGROUND: The roles of antioxidants in the placenta and genetic susceptibility to oxidant chemicals in relation to neonatal birth weight have not been elucidated. We determined whether the level of placental manganese superoxide dismutase (MnSOD) and its genetic polymorphism plays any role in oxidative stress and neonatal birth weight. METHODS: We measured placental MnSOD and determined MnSOD genetic polymorphism among 108 pregnant women who were hospitalized for delivery and their singleton live births in Korea. Main outcome measurements are maternal urinary malondialdehyde (MDA) and birth weight. RESULTS: Maternal urinary concentrations of MDA were significantly associated with neonatal birth weight (P=0.04). The enzyme level of placental MnSOD was also significantly associated with MDA concentration (P=0.04) and neonatal birth weight (P< 0.01). We observed dose-response relationships between placental MnSOD and maternal urinary MDA, and neonatal birth weight after adjusting for maternal weight, height, age, and neonatal sex. After controlling for covariates, MnSOD variant genotype increased maternal urinary MDA concentrations (P< 0.01) and reduced birth weight by 149 gm (P=0.08). CONCLUSIONS: This study demonstrates that the placental level of MnSOD during pregnancy significantly affects fetal growth by reducing oxidative stress, and that genetic polymorphism of MnSOD probably modulate the effects of oxidants on fetal growth.

Nitric oxide production increases during normal pregnancy and decreases in preeclampsia.

To investigate the changes in nitric oxide (NO) production during and after normal pregnancy and in pregnancies complicated by preeclampsia, we measured serum nitrates and nitrites (NOx) concentrations and serum iron markers in 347 subjects. Serum NOx concentrations were determined after reduction of nitrates to nitrites using the Griess reaction. Serum iron and serum ferritin were assayed using an automatic chemical analyzer and a chemiluminescence method. Serum NOx concentrations were significantly higher in the first trimester (117.3 +/- 31.4 microM) than in nonpregnant women (23.8 +/- 7.1 microM). High NOx concentrations persisted throughout normal pregnancy, irrespective of serum ferritin concentrations, and returned to nonpregnant levels by 9-12 wk postpartum. Mean NOx concentrations in preeclamptic women were 43.1 +/- 12.7 microM, which were significantly lower than those in the gestation age-matched normal pregnant women (249.7 +/- 51.3 microM). In summary, NO production increases with advancing gestation during normal pregnancy and decreases in preeclampsia, regardless of serum ferritin concentrations. Elevated NOx concentrations during pregnancy return to normal within 12 wk after delivery.