The effect of apolipoprotein E polymorphism on lipid levels in Korean adults

The aim of this study was to determine the effects of polymorphisms in the apolipoprotein E gene (APOE) on lipid levels in Korean adults and to investigate the interactions between these polymorphisms and environmental factors in determining lipid levels. We performed a cross-sectional study of 1,900 subjects (668 men and 1,232 women; 45-74 yr old) in Namwon, Korea, in 2004. APOE polymorphisms were determined by polymerase chain reaction and restriction enzyme analysis. Carriers of the APOE*E2 (E2) allele had significantly lower total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations than did carriers of the APOE*E3 (E3) or APOE*E4 (E4) alleles, regardless of gender. The APOE allele type had significant effect on high-density lipoprotein cholesterol (HDL-C) and triglyceride levels in women, but not in men. The effect of APOE allele type on HDL-C levels was modified by age in women. In addition, in men, the effect of APOE allele type on triglyceride levels was modified by smoking. These findings highlight the important effect of gene-environment interactions on lipid levels.     

The relationship between maximal urethral closure pressure and functional urethral length in anterior vaginal wall prolapse patients according to stage and age

MUCP (Maximal urethral closure pressure) is known to be increased in patients with vaginal wall prolapse due to the mechanical obstruction of the urethra. However, urethral function following reduction has not yet been completely elucidated. Predicting postoperative urethral function may provide patients with important, additional information prior to surgery. Thus, this study was performed to evaluate the relationship between MUCP and functional urethral length (FUL) according to stage and age in anterior vaginal wall prolapse patients. 139 patients diagnosed with anterior vaginal wall prolapse at Yonsei University Medical College (YUMC) from March 1999 to May 2003 who had underwent urethral pressure profilometry following reduction were included in this study. The stage of pelvic organ prolapse (POP) was determined according to the dependent portion of the anterior vaginal wall (Aa, Ba). (By International Continence Society's POP Quantification system) Patients were divided into one of four age groups: patients in their 40s (n = 13), 50s (n = 53), 60s (n = 54), and 70 and over (n = 16). No difference in MUCP was found between the age groups. The FUL of patients in their 40s was shorter than that of patient's in their 50s and 60s. Patients were also divided into stages: stage II (n = 35), stage III (n = 76), and stage IV (n = 25). No significant difference in MUCP was found according to stage and FUL. However, a significant difference was noted between stage III and IV as stage IV was longer. Anterior vaginal wall prolapse is known to affect urethral function due to prolapse itself, but according to our study, prolapse itself did not alter urethral function. This suggests that, regardless of age and stage, prolapse corrective surgery does not affect the urethral function.     

Methods for derivation of human embryonic stem cells

The expanded blastocysts, developed from 2PN-stage embryos, are generally divided into three categories: a good blastocyst containing a large and distinguishable inner cell mass (ICM), a blastocyst with a small and distinct ICM, and a blastocyst with a poorly defined ICM. In this study, we introduce methods for the derivation of human embryonic stem cells (hESCs) depending on the quality of the blastocysts. An immunosurgical method was used for the good expanded blastocysts. This method, however, raises the probability of ICM loss in cases of hESC derivation from blastocysts with smaller or indistinct ICMs. Furthermore, this method is also associated with a risk of the contamination of the hESCs with animal pathogens. To overcome these shortcomings, the partial- or whole-embryo culture method was used. For blastocysts with no visible ICM, the whole-embryo culture method was used to establish hESCs via the seeding of the entire blastocyst without its zona pellucida directly on a STO feeder layer. However, trophectodermal overgrowth tends to hinder the expansion of the ICM during the initial steps of hESC derivation. Therefore, the partial-embryo culture method was developed to establish hESCs from blastocysts with smaller ICMs. The surgical isolation of the region containing the ICM with an ultra-fine glass pipette alleviates trophectoderm overgrowth. This method is also applicable to blastocysts with large and distinct ICMs, and the efficiency of this method is comparable to that of the immunosurgical method.     

A pilot study of bortezomib in Korean patients with relapsed or refractory myeloma

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.     

Cervical facet joint injections in the neck and shoulder pain

The effects from cervical facet joint injections in those patients who have been complaining cervical zygapophyseal joint pain were compared. The patients were diagnosed originally as myofascial pain syndrome (MPS), cervical herniated nucleus pulposus (HNP), and whiplash-associated disorders (WAD). Patients with the zygapophyseal joints pain of C5-6 and C6-7 were classified by their pain origin as MPS, HNP, and WAD. All patients had been undergone cervical zygapophyseal joints injections with the mixture of lidocaine and triamcinolone unilaterally or bilaterally through the posterior approach under C-arm imaging guide. The therapeutic effects were compared with reduction of numeric rating scale (NRS) of pain before and immediately after blockade and symptom-free periods in each group after 12 months. Symptom durations before injections were 16.1+/-9.6, 4.6+/-1.9 and 4.1+/-1.1 months in each MPS, HNP, and WAD groups. The reductions of NRS immediately after the blockade among the three groups were not different. However, the symptom-free duration after blockade lasted longer in the HNP group than the other two groups. In patients with cervical zygapophyseal pain syndromes, the analgesic effect from cervical facet joint blocks lasted longer in cervical HNP than MPS or WAD.     

The effects of the acupuncture treatment for smoking cessation in high school student smokers

The use of alternative medicine for smoking cessation have been increasing steadily in recent years. A series of clinical group studies was performed to clarify the effect, outcome and success rate of an acupuncture treatment for smoking cessation. This study was conducted for four weeks using 238 smoking students at 2 high schools. The subjects were separated into two groups: 159 students were treated with acupuncture on the anti-smoking acupoints of the ear, which is known to be effective for cessation of smoking (case group), and 79 students were treated at other sites of the ear (control group). The acupuncture treatment was alternately administered at each side of the ears on a weekly basis for 4 weeks. The smoking cessation success was only 1 case (0.6%) in the case group and none in the control group after 4 weeks. The change in the taste of tobacco and the intensity of the desire to smoke were not significantly different between the case and control groups, but the case group showed a tendency of reduction in the taste of tobacco and the intensity of the desire to smoke. In addition, the reduction in cigarette consumption was not significant, but the tendency of reduction in the study group was significant. It is believed that the site of auricular acupuncture for smoking cessation is not important. However, there was a significant tendency in terms of the reduction in cigarette consumption, the taste of tobacco and the intensity of the desire to smoke in the case group, indicating that auricular acupuncture in smoking cessation has some effect.     

Isolation of endothelial progenitor cells from cord blood and induction of differentiation by ex vivo expansion

Endothelial progenitor cells (EPCs) have been reported to possess the capacity to colonize vascular grafts and hold promise for therapeutic neovascularization. However, limited quantities of EPCs have been the major factor impeding effective research on vasculoangiogenesis. In this study, cytokine and culture conditions necessary for the provision of large quantities of endothelial cells (ECs) were investigated. Cord blood was collected from 18 normal full-term deliveries and CD34+ cells were isolated by MACS system (Miltenyi Biotech, Bergish-Gladbach, Germany). To evaluate the effect of cytokines, CD34+ cells were cultured with various cytokine combinations, such as stem cell factor (SCF), flt3-ligand (FL), and thrombopoietin (TPO) with vascular endothelial growth factor (VEGF), interleukin-1 beta , fibroblast growth factor-basic (FGF-b) as basic cytokines. The quantities of non-adherent and adherent cells were the greatest with SCF, FL and TPO. The addition of TPO to all other cytokines significantly increased the number of non-adherent and adherent cells (p< 0.05, Wilcoxon rank sum test). After four weeks of culture, adherent cells expressed endothelial specific markers such as KDR, CD31 and CD62E. Typical morphology of ECs was observed during culture, such as cord-like structure and cobblestone appearance, suggesting that the adherent cells were consistent with ECs. In this study, the experimental conditions that optimize the production of ECs for therapeutic neovascularization were described. And it was possibly suggested that TPO plays a major role in differentiation from EPCs to ECs.     

Hematopoietic differentiation of embryoid bodies derived from the human embryonic stem cell line SNUhES3 in co-culture with human bone marrow stromal cells

Human embryonic stem (ES) cells can be induced to differentiate into hematopoietic precursor cells via two methods: the formation of embryoid bodies (EBs) and co-culture with mouse bone marrow (BM) stromal cells. In this study, the above two methods have been combined by co-culture of human ES-cell-derived EBs with human BM stromal cells. The efficacy of this method was compared with that using EB formation alone. The undifferentiated human ES cell line SNUhES3 was allowed to form EBs for two days, then EBs were induced to differentiate in the presence of a different serum concentration (EB and EB/high FBS group), or co- cultured with human BM stromal cells (EB/BM co-culture group). Flow cytometry and hematopoietic colony-forming assays were used to assess hematopoietic differentiation in the three groups. While no significant increase of CD34+/CD45- or CD34+/CD38- cells was noted in the three groups on days 3 and 5, the percentage of CD34+/CD45- cells and CD34+/ CD38- cells was significantly higher in the EB/BM co-culture group than in the EB and EB/high FBS groups on day 10. The number of colony-forming cells (CFCs) was increased in the EB/BM co-culture group on days 7 and 10, implying a possible role for human BM stromal cells in supporting hematopoietic differentiation from human ES cell-derived EBs. These results demonstrate that co-culture of human ES-cell-derived EBs with human BM stromal cells might lead to more efficient hematopoietic differentiation from human ES cells cultured alone. Further study is warranted to evaluate the underlying mechanism.