Effects of behavior modification on body image, depression and body fat in obese Korean elementary school children

This study was performed to investigate the effects of behavior modification on body image, depression and body fat in obese elementary school children. Sixty-two elementary students of the 4th to 6th grade were selected from two different Seoul schools. Thirty-four children in one school were designated as the experimental group, and 28 children from the other school as the control group. The experimental group received 60 - 70 minutes of behavior modification, once a week, for 8 weeks. The control group received neither management nor treatment. The results indicated a significant improvement of body image and a reduction in the increase rate of body fat for the experimental group. This finding strongly supports the theory that behavior modification can be used as an effective strategy in the treatment of obese children.     

Proper cut-off value of free to total PSA ratio for detection of prostate cancer in Korean men

To assess whether the free-to-total prostate specific antigen (PSA) ratio (F/T PSA ratio) would enhance prostate cancer detection in Korean men with serum total PSA levels between 4 and 20 ng/ml. Methods: A total of 240 consecutive patients whose serum PSA levels were between 4 and 20 ng/ml were enrolled in this two-year study. All patients underwent ultrasound-guided transrectal biopsies of the prostate gland. The F/T PSA ratio was measured using the Roche immunoassay. Results: Of the 240 patients, 202 (84%) had benign histologies, while 38 (16%) had prostate cancer. The two patient groups were well matched for age. The mean F/T PSA ratio showed a statistically significant difference between the two groups: in the benign histology group it was 0.14 (0.04 - 0.37), and 0.10 (0.08 - 0.20) in the prostate cancer group (p < 0.05). Out of the 183 patients with a PSA level between 4-10 ng/ml, the mean F/T PSA ratios were 0.14 and 0.11 in the benign histology (n=158) and prostate cancer groups (n=25), respectively (p < 0.05). From the 57 patients with a PSA level between 10 - 20 ng/ml, the mean F/T PSA ratios were 0.14 and 0.10 in the benign histology (n=44) and prostate cancer groups (n=13), respectively (p < 0.05). Overall, when the cut-off value of the F/T PSA ratio was 0.10, the sensitivity and specificity were 75.0% and 76.5%, while for the cut-off value of 0.15 they were 83.3% and 39.7% respectively. Conclusion: Our data demonstrated the usefulness of the free to total PSA ratio in distinguishing benign prostate disease and cancer disease, hence eliminating unnecessary biopsies. It is recommended that a cut-off value for the F/T PSA ratio of 0.10 be applied to Korean men which this is lower than the value used in Western countries.     

Delivery of a hammerhead ribozyme specifically down-regulates the production of fibrillin-1 by cultured dermal fibroblasts

The hammerhead ribozyme is a small catalytic RNA molecule. Potential hammerhead ribozymes that possess a catalytic domain and flanking sequence complementary to a target mRNA can cleave in trans at a putative cleavage site within the target molecule. We have investigated the potential of hammerhead ribozymes to down-regulate the product of the fibrillin-1 gene (FBN1). Fibrillin is a 347 kDa glycoprotein that is a major constituent of the elastin-associated microfibrils. Mutations in the FBN1 gene are responsible for Marfan syndrome (MFS), a common systemic disorder of the connective tissue. Many FBN1 mutations responsible for MFS appear to act in a dominant-negative fashion, raising the possibility that reduction of the amount of product from the mutant FBN1 allele might be a valid therapeutic approach for MFS. A trans-acting hammerhead ribozyme (FBN1-RZ1) targeted to the 5' end of the human FBN1 mRNA has been designed and synthesized, and shown to cleave its target efficiently in vitro. FBN1-RZ1 cleavage is magnesium dependent and efficient at both 37 and 50 degrees C. Delivery of the FBN1-RZ1 ribozyme into cultured dermal fibroblasts, by receptor- mediated endocytosis of a ribozyme-transferrin-polylysine complex, specifically reduces both cellular FBN1 mRNA and the deposition of fibrillin in the extracellular matrix. These results suggest that the use of hammerhead ribozymes is a valid approach to the study of fibrillin gene expression and possibly to the development of a therapeutic approach to MFS.      

Clinical implications of quantitative electroencephalography and current source density in patients with Alzheimer's disease

This study examined whether quantitative electroencephalography (qEEG) and current source density (CSD) can be used to evaluate symptom severity in Alzheimer's disease (AD) patients. Thirty AD patients (13 mild and 17 moderate severity) and 30 normal control (NC) subjects were recruited. The Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet and the Global Deterioration Scale were measured. qEEG and CSD data were analyzed in five frequency bands: delta (1-3?Hz), theta (4-7?Hz), alpha (8-12?Hz), beta (13-25?Hz), and gamma (30-50?Hz). Compared with the NC subjects, the moderate AD patients had significantly increased theta and decreased beta power. Compared with the mild AD patients, the moderate AD patients had significantly decreased beta power. In the AD patients, the theta power was significantly correlated with a poor performance for global cognition; however, beta power was positively correlated with a good performance for global cognition, attention, memory, visuospatial function, and executive function. The CSD of the theta band in the superior temporal gyrus, transverse temporal gyrus, insula, postcentral gyrus, cuneus, and lingual gyrus was significantly different between NC subjects and moderate AD patients and between mild and moderate AD patients. The theta CSD of these regions was significantly correlated with a poor performance for global cognition, memory, visuospatial function, execution, and language. The results suggest that qEEG and the CSD of the theta and beta bands are useful biological markers in AD patients.     

AMPK activation reduces vascular permeability and airway inflammation by regulating HIF/VEGFA pathway in a murine model of toluene diisocyanate-induced asthma

Background

Occupational asthma is characterized by airway inflammation and hyperresponsiveness associated with increased vascular permeability. AMP-activated protein kinase (AMPK) has been suggested to be a novel signaling molecule modulating inflammatory responses.

Objective

We sought to evaluate the involvement of AMPK in pathogenesis of occupational asthma and more specifically investigate the effect and molecular mechanisms of AMPK activation in regulating vascular permeability.

Methods

The mechanisms of action and therapeutic potential of an AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) were tested in a murine model of toluene diisocyanate (TDI)-induced asthma.

Results

AICAR attenuated airway inflammation and hyperresponsiveness increased by TDI inhalation. Moreover, TDI-induced increases in levels of hypoxia-inducible factor (HIF)-1α, HIF-2α, vascular endothelial growth factor A (VEGFA), and plasma exudation were substantially decreased by treatment with AICAR. Our results also showed that VEGFA expression was remarkably reduced by inhibition of HIF-1α and HIF-2α with 2-methoxyestradiol (2ME2) and that an inhibitor of VEGFA activity, CBO-P11 as well as 2ME2 significantly suppressed vascular permeability, airway infiltration of inflammatory cells, and airway hyperresponsiveness induced by TDI. In addition, AICAR reduced reactive oxygen species (ROS) generation and levels of malondialdehyde and T-helper type 2 cytokines (IL-4, IL-5, and IL-13), while this agent enhanced expression of an anti-inflammatory cytokine, IL-10.

Conclusions

These results suggest that AMPK activation ameliorates airway inflammatory responses by reducing vascular permeability via HIF/VEGFA pathway as well as by inhibiting ROS production and thus may be a possible therapeutic strategy for TDI-induced asthma and other airway inflammatory diseases.     

Multiple recombinant antigens of Clonorchis sinensis for serodiagnosis of human clonorchiasis

Antigenic proteins from Clonorchis sinensis have been previously purified and evaluated for their antigenicity to enable the serodiagnosis of clonorchiasis. Though they were of high specificity, molecularly defined proteins were reported to be less sensitive as single antigens than crude antigen. To resolve this issue, 11 clones were selected by immunoscreening an adult C. sinensis cDNA library using infected human sera. Mixed antigens were prepared using recombinant proteins of positive clones and investigated for antigenicity by immunoblotting against C. sinensis- and helminth-infected patient sera. A mixed antigen of recombinant 28 and 26 kDa glutathion S-transferases (Cs28GST and Cs26GST) produced 76% sensitivity and 95% specificity. Furthermore, a triple mix of recombinant Cs26GST and Cs28GST with vitelline precursor protein pushed up the sensitivity to 87% and maintained specificity at 95%. It is proposed that multiple antigen mixes should be further studied to develop rapid serodiagnostic test kits for the serodiagnosis of human clonorchiasis.     

T-cell immunoglobulin and mucin domain 3 genetic polymorphisms are associated with rheumatoid arthritis independent of a shared epitope status

The aim of this study was to investigate T-cell immunoglobulin and mucin domain 3 (TIM3) genetic polymorphisms and rheumatoid arthritis (RA) according to the shared epitope (SE) status. Six single nucleotide polymorphisms (SNPs: rs11742259 [C/T], rs10515746 [C/A], rs35960726 [A/G], rs1036199 [A/C], rs4704846 [A/G], and rs11134551 [A/G]) in the TIM3 gene from 366 RA patients and 389 healthy controls were investigated using the real-time polymerase chain reaction method. Associations between these SNPs and clinical manifestations (including SE status) were investigated using the SPSS program and Haploview. Polymorphisms of rs35690726 (AG+ GG vs AA: 8.2% vs 1.8%, p(c) < 0.001) were significantly associated with RA with or without SE (p(c) < 0.001 or p(c) = 0.009, respectively). Polymorphisms of rs11742259 (p(c) = 0.003) and rs1036199 (p(c) = 0.012) were significantly different in RA patients with SE, but not in those without SE. In haplotype analysis with a permutation test for the first 4 SNPs (rs11742259, rs10515746, rs35690726, and, rs1036199), CCAA, CCGA, CCGC, and CAAA haplotypes were significantly associated with RA. The clinical characteristics of RA patients were not significantly associated with any TIM3 polymorphism. TIM3 genetic polymorphisms may have a role in the development of RA regardless of a shared epitope status.     

S-Nitrosoglutathione reduces oxidative injury and promotes mechanisms of neurorepair following traumatic brain injury in rats

Background

Burn survivors develop long-term cognitive impairment with increased inflammation and apoptosis in the brain. Gelsolin, an actin-binding protein with capping and severing activities, plays a crucial role in the septic response. We investigated if gelsolin infusion could attenuate neural damage in burned mice.

Methods

Mice with 15% total body surface area burns were injected intravenously with bovine serum albumin as placebo (2 mg/kg), or with low (2 mg/kg) or high doses (20 mg/kg) of gelsolin. Samples were harvested at 8, 24, 48 and 72 hours postburn. The immune function of splenic T cells was analyzed. Cerebral pathology was examined by hematoxylin/eosin staining, while activated glial cells and infiltrating leukocytes were detected by immunohistochemistry. Cerebral cytokine mRNAs were further assessed by quantitative real-time PCR, while apoptosis was evaluated by caspase-3. Neural damage was determined using enzyme-linked immunosorbent assay of neuron-specific enolase (NSE) and soluble protein-100 (S-100). Finally, cerebral phospho-ERK expression was measured by western blot.

Results

Gelsolin significantly improved the outcomes of mice following major burns in a dose-dependent manner. The survival rate was improved by high dose gelsolin treatment compared with the placebo group (56.67% vs. 30%). Although there was no significant improvement in outcome in mice receiving low dose gelsolin (30%), survival time was prolonged against the placebo control (43.1 ± 4.5 h vs. 35.5 ± 5.0 h; P < 0.05). Burn-induced T cell suppression was greatly alleviated by high dose gelsolin treatment. Concurrently, cerebral abnormalities were greatly ameliorated as shown by reduced NSE and S-100 content of brain, decreased cytokine mRNA expressions, suppressed microglial activation, and enhanced infiltration of CD11b+ and CD45+ cells into the brain. Furthermore, the elevated caspase-3 activity seen following burn injury was remarkably reduced by high dose gelsolin treatment along with down-regulation of phospho-ERK expression.

Conclusion

Exogenous gelsolin infusion improves survival of mice following major burn injury by partially attenuating inflammation and apoptosis in brain, and by enhancing peripheral T lymphocyte function as well. These data suggest a novel and effective strategy to combat excessive neuroinflammation and to preserve cognition in the setting of major burns.     

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

Objective

Recent studies have demonstrated that lymphovascular space invasion (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis and poor clinical outcome of women with epithelial ovarian cancer. Given the suspected role of estrogen in promoting ovarian cancer metastasis, we examined potential links between estrogen receptor and LVSI in high-grade serous ovarian carcinoma.

Methods

Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA ploidy, and S-phase fraction was examined for 121 cases of stage I–IV high-grade serous ovarian carcinoma samples obtained at primary cytoreductive surgery. Biomarker expression was correlated to LVSI and survival outcomes.

Results

LVSI was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53 (71.4%), HER2 (68.3%), EGFR (52.1%), MDR-1 (14.3%), and PR (8.9%). ER expression was positively correlated to PR expression (r = 0.31, p = 0.001). LVSI was only correlated with ER (odds ratio 6.27, 95%CI 1.93–20.4, p = 0.002) but not with other biomarkers. In multivariate analysis, ER remained significantly associated with LVSI (p = 0.039). LVSI remained a significant prognostic factor for decreased progression-free survival (HR 3.01, 95%CI 1.54–5.88, p = 0.001) and overall survival (HR 2.69, 95%CI 1.18–6.23, p = 0.021) while ER-expression did not remain as a significant variable in multivariate analysis.

Conclusion

Our data demonstrated that estrogen receptor was positively correlated with LVSI that was an independent prognostic indicator of poor survival outcomes of high-grade serous ovarian carcinoma. This study emphasizes the importance of estrogen pathway in promoting lymphatic or vascular spread of high-grade serous ovarian carcinoma.     

Successful Treatment of Nongestational Choriocarcinoma in a 15-Year-Old Girl: A Case Report

BackgroundNongestational choriocarcinoma is a rare ovarian malignancy with a prognosis worse than that of gestational choriocarcinoma. Debulking surgery is the primary treatment for ovarian carcinoma. However, fertility preservation is important in young women.CaseA 15-year-old girl with no sexual experience was admitted for abnormal uterine bleeding. Ultrasonography showed a solid mass in the right ovary and her serum β-human chorionic gonadotrophin levels were markedly elevated. We performed right oophorectomy, omentectomy, and peritoneal washing cytology. The uterus and left adnexa were preserved. She was diagnosed with nongestational choriocarcinoma, stage IIA. She received adjuvant chemotherapy (etoposide, methotrexate, actinomycin, cyclophosphamide, and oncovin regimen) and has been disease-free for more than 5 years.Summary and ConclusionFertility-sparing surgery combined with chemotherapy is an acceptable treatment option for young patients with locally advanced nongestational choriocarcinoma.