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Biomedical subjects

J R Kim

Publications and source records attributed to J R Kim.

At least 19 recordsLinked to original sources

Parathyroid hormone (1-34) augments angiopoietin-1 expression in human osteoblast-like cells.

Parathyroid hormone (PTH) is a major regulatory factor in skeletal physiology. However, the molecular mechanism underlying the effects of PTH on bones has yet to be elucidated in detail. Recently, some reports have demonstrated the crucial role of bone vasculature with regard to bone density. Angiopoietin-1 (Ang-1), along with VEGF, has been established as a primary angiogenic regulatory agent. In this study, we have attempted to characterize the effects of PTH (1-34) on Ang-1 expression and signaling molecules, employing primary-cultured human osteoblast-like cells. Quiescent osteoblasts were exposed to PTH (1-34), after which Ang-1 expression was determined at the mRNA and protein levels. Reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated that Ang-1 mRNA expression increased as the result of PTH (1-34) treatment. The expression of the Ang-1 protein was also augmented as the result of treatment with PTH (1-34). An adenylyl cyclase activator, forskolin, was shown to induce Ang-1 mRNA expression, whereas the protein kinase A inhibitor, H-89, blocked the PTH (1-34)-mediated expression of Ang-1 mRNA. These findings indicate that PTH (1-34)-mediated Ang-1 expression involves adenylyl cyclase-protein kinase A dependent signaling. Our observations also show that Ang-1 may perform a crucial role in the effects of PTH (1-34) on bones, possibly involving alterations in bone vasculature.

Angiopoietin-1↗

Subcutaneous hyalohyphomycosis due to Cephalotheca foveolata in an immunocompetent host.

We report the first case of subcutaneous hyalohyphomycosis caused by the genus Cephalotheca, which has not been reported to cause human infection. A 67-year-old immunocompetent farmer presented with a 10-year history of verrucous erythematous plaques on the right foot dorsum, great toe, heel and sole. Histopathology of the lesions revealed chronic granulomatous inflammation with numerous nonpigmented fungal spores in the dermis. Cultures of biopsy specimens on Sabouraud's dextrose agar for 2 weeks developed into yellowish brown, velvety colonies that subsequently turned black after 8 weeks because of the production of black cleistothecia indicating the teleomorph. On the basis of mycological features, scanning electron microscopic morphology and molecular analysis data, a new species of Cephalotheca was identified and designated Cephalotheca foveolata. Because there was no response to the antifungal agents administered, the patient was successfully treated by surgical excision with skin graft.

Aged↗

Parameter sensitivity analysis for activated sludge models No. 1 and 3 combined with one-dimensional settling model.

The aim of this study was to suggest a sensitivity analysis technique that can reliably predict effluent quality and minimize calibration efforts without being seriously affected by influent composition and parameter uncertainty in the activated sludge models No. 1 (ASM1) and No. 3 (ASM3) with a settling model. The parameter sensitivities for ASM1 and ASM3 were analyzed by three techniques such as SVM-Slope, RVM-SlopeMA, and RVM-AreaCRF. The settling model parameters were also considered. The selected highly sensitive parameters were estimated with a genetic algorithm, and the simulation results were compared as deltaEQ. For ASM1, the SVM-Slope technique proved to be an acceptable approach because it identified consistent sensitive parameter sets and presented smaller deltaEQ under every tested condition. For ASM3, no technique identified consistently sensitive parameters under different conditions. This phenomenon was regarded as the reflection of the high sensitivity of the ASM3 parameters. But it should be noted that the SVM-Slope technique presented reliable deltaEQ under every influent condition. Moreover, it was the simplest and easiest methodology for coding and quantification among those tested. Therefore, it was concluded that the SVM-Slope technique could be a reasonable approach for both ASM1 and ASM3.

Algorithms↗

Identification of the adverse effect of nitrate on the phosphate release rate and improvement of EBPR process models.

The adverse effect of nitrate on the phosphate release rate in the anaerobic phase was observed and was hardly explainable with conventional EBPR process models. Four possible mechanisms were proposed including substrate competition, reduced fermentation, parallel reaction and sequential reaction. Batch experiments were designed and conducted to identify the dominant mechanism. Results showed that the sequential reaction was the only possible mechanism where only denitrification occurred if any nitrate existed in the anaerobic phase. Then the phosphate release following after the nitrate was completely removed. Nitrate inhibition effect was added into the PHA storage rate to incorporate the sequential reaction in the conventional ASM3 plus EAWAG bio-P module (ASM3 + P). Nitrate inhibition coefficient, K(I,NO,PAO) was found to be as low as 0.05 mg/L. This correlated well with experimental observation where no also meant that the anaerobic compartment of a continuous flow reactor could be seriously affected by the residual nitrate contained in the sludge recycle flow. This phenomenon caused overestimation of the phosphate uptake rate and consequently underestimation of PO4(3-) -P concentration. This problem was resolved by incorporation of a nitrate inhibition term in the ASM3 + P for more accurate simulation of the EBPR process.

Bacteria, Anaerobic↗

Full-cyclic control strategy of SBR for nitrogen removal in strong wastewater using common sensors.

A full-cyclic automatic control strategy for sequencing batch reactors (SBR) was proposed using only common sensors such as ORP, DO and pH. The main objective was to develop a generally applicable and robust control strategy. To accomplish this, various control schemes found in the literature or suggested by authors were examined at diverse ammonia loads and SCOD/NH4(+)-N ratios. Advantages and constraints of each scheme were discussed and compared. Ammonia load was estimated with DO lag time during the aerobic stage, and then the influent pump was manipulated to meet the desired load at the next anoxic stage. A partial denitrification scheme was chosen for the anoxic stage period control, to save anoxic time and external carbon. For external carbon dosage control, intermittent feeding at each anoxic stage was concluded to be a suitable scheme. The anoxic stage period could be successfully controlled by the combination of pH increase and DO increase. Every suggested control scheme was incorporated into a full-cyclic control strategy and tested at 0.02, 0.035, 0.08 kg NH4(+)-N/m3/sub-cycle. From the results, it is expected to perform unmanned automatic SBR operation with this strategy.

Ammonia↗

Forecasting influent flow rate and composition with occasional data for supervisory management system by time series model.

The information on the incoming load to wastewater treatment plants is not often available to apply modelling for evaluating the effect of control actions on a full-scale plant. In this paper, a time series model was developed to forecast flow rate, COD, NH4(+)-N and PO4(3-)-P in influent by using 250 days data of field plant operation data. The data for 150 days and 100 days were used for model development and model validation, respectively. The missing data were interpolated by the spline method and the time series model. Three different methods were proposed for model development: one model and one-step to seven-step ahead forecasting (Method 1); seven models and one-step-ahead forecasting (Method 2); and one model and one-step-ahead forecasting (Method 3). Method 3 featured only one-step-ahead forecasting that could avoid the accumulated error and give simple estimation of coefficients. Therefore, Method 3 was the reliable approach to developing the time series model for the purpose of this research.

Forecasting↗

Monitoring of pH inhibition on microbial activity in a continuous flow reactor by pseudo toxic concentration (C(PT)) concept and time delay model.

The pseudo toxic concentration (C(PT)) concept was introduced as a quantification method to describe pH as an inhibitor concentration. In this research, the applicability of the C(PT) concept model for the detection of pH inhibitions was expanded for a continuous flow activated sludge reactor. A pilot equipped with an inhibition detection system was installed. Inhibitory wastewater was injected for 1 h and the relative activity was calculated by the maximum respiration rate. At the same time, the coefficients for the C(PT) concept model were estimated. At the dynamic conditions, the estimated relative activity by the C(PT) concept model showed time lag compared to the measured one. However, the time lag problem was successfully resolved by introducing a transfer function into the C(PT) concept model. The C(PT) concept model combined with a transfer function (C(PT) + TF model) successfully tracked the variation of the relative activity under dynamic conditions. The C(PT) + TF model could detect 50% inhibition faster than the respirometry based method by approximately 10 min. Moreover, it had additional advantages such as being inexpensive, easy to install and simple to operate. In conclusion, the C(PT) + TF model was an effective and convenient detection method of pH inhibition.

Bioreactors↗

Deletions involving long-range conserved nongenic sequences upstream and downstream of FOXL2 as a novel disease-causing mechanism in blepharophimosis syndrome.

The expression of a gene requires not only a normal coding sequence but also intact regulatory regions, which can be located at large distances from the target genes, as demonstrated for an increasing number of developmental genes. In previous mutation studies of the role of FOXL2 in blepharophimosis syndrome (BPES), we identified intragenic mutations in 70% of our patients. Three translocation breakpoints upstream of FOXL2 in patients with BPES suggested a position effect. Here, we identified novel microdeletions outside of FOXL2 in cases of sporadic and familial BPES. Specifically, four rearrangements, with an overlap of 126 kb, are located 230 kb upstream of FOXL2, telomeric to the reported translocation breakpoints. Moreover, the shortest region of deletion overlap (SRO) contains several conserved nongenic sequences (CNGs) harboring putative transcription-factor binding sites and representing potential long-range cis-regulatory elements. Interestingly, the human region orthologous to the 12-kb sequence deleted in the polled intersex syndrome in goat, which is an animal model for BPES, is contained in this SRO, providing evidence of human-goat conservation of FOXL2 expression and of the mutational mechanism. Surprisingly, in a fifth family with BPES, one rearrangement was found downstream of FOXL2. In addition, we report nine novel rearrangements encompassing FOXL2 that range from partial gene deletions to submicroscopic deletions. Overall, genomic rearrangements encompassing or outside of FOXL2 account for 16% of all molecular defects found in our families with BPES. In summary, this is the first report of extragenic deletions in BPES, providing further evidence of potential long-range cis-regulatory elements regulating FOXL2 expression. It contributes to the enlarging group of developmental diseases caused by defective distant regulation of gene expression. Finally, we demonstrate that CNGs are candidate regions for genomic rearrangements in developmental genes.

Animals↗

The clinicopathological significance of inferior mesenteric lymph node metastasis in colorectal cancer.

AIMS: There are few studies reporting survival or recurrence patterns in colorectal cancer patients with inferior mesenteric lymph node metastasis (IMLN+). The present study evaluated the prognostic significance of patients being IMLN+ or IMLN- in colorectal cancer. METHODS: Survival, recurrence pattern and treatment protocols were compared between 63 IMLN+ patients and 108 IMLN- patients with stage III and IV rectal and sigmoid cancer undergoing curative surgery. Lymph node sampling was routinely performed prior to inferior mesenteric artery ligation and excision flush with aorta. Limited principal node dissection including IMLN was performed in cases of identified node metastasis. RESULTS: The 5-year disease-free survival rates were 50% in IMLN- and 31% in IMLN+ patients (P=0.004). The 5-year disease-free survival rate was greater in the N1 group than the N2 group (P=0.038). Cox regression analysis showed IMLN+, lymphovascular tumour invasion, T4, M1, and pre-operative serum CEA level over 6 ng/ml were independently associated with unfavorable disease-free survival. The prognostic significance of M category was greater when the IMLN+ was included in the M1 as opposed to the N category. In patients undergoing absolute curative surgery, post-operative recurrence rates were 34% for IMLN- and 57% for IMLN+ patients (P=0.009; OR, 2.611; 95% CI, 1.313-5.194). For IMLN+ patients, post-operative adjuvant treatment independently correlated with disease-free survival (P=0.029). CONCLUSIONS: IMLN+ is an independent survival factor enhancing the prognostic significance of the M category in the AJCC staging. Curative radical surgery and post-operative chemoradiotherapy appears to be warranted for IMLN+ colorectal cancer patients as it resulted in 5-year disease-free survival rates of up to 31% compared to 50% in IMLN- patients.

Adult↗

Expression of cyclooxygenase 2, microsomal prostaglandin E synthase 1, and EP receptors is increased in rat oesophageal squamous cell dysplasia and Barrett's metaplasia induced by duodenal contents reflux.

BACKGROUND AND AIM: It is known that bile acids can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. A large body of genetic and biochemical evidence indicate that the biosynthetic pathway of prostaglandin E2 (PGE2) may play an important role in human and rodent tumours. Therefore, we examined the expression pattern of cyclooxygenase 1 (COX-1), COX-2, and microsomal prostaglandin E synthase 1 (mPGES-1), as well as EP receptor subtypes in rat oesophageal lesions induced by duodenal contents reflux. METHODS: Oesophagoduodenal anastomosis was performed in rats to induce duodenal contents reflux. We examined histological changes and expression of COX-1, COX-2, mPGES-1, and EP receptor subtypes in the oesophagus by immunohistochemistry and reverse transcription-polymerase chain reaction. RESULTS: Normal control oesophageal tissues showed COX-1 expression in subepithelial stromal cells, including endothelial cells and muscular cells, and did not reveal expression of COX-2 or mPGES-1. In the case of squamous cell lesions, immunoreactivity of COX-1 was similar to that of normal lesions, and COX-2 was maximally expressed around the vascular papillae of tissues showing dysplasia and surrounding epithelial layer and basal layer. mPGES-1 was highly expressed in stromal cells with COX-2 expression. In the case of Barrett's oesophagus, COX-2 and mPGES-1 were predominantly in subepithelial stromal cells. mRNA levels of COX-2, mPGES-1, EP2, EP3, and EP4 were higher in the experimental groups than in controls. CONCLUSIONS: We suggest that the biosynthetic pathway of PGE2 may play an important role in oesophageal squamous cell dysplasia and glandular metaplasia induced by duodenal contents reflux.

Animals↗

External carbon feeding strategy for enhancing nitrogen removal in SBR.

Effective method for feeding an external carbon source (ECS) in SBR was investigated to enhance denitrification based on modifying the anoxic/aerobic sub-cycle for swine wastewater treatment. The wastewater discharged from the scraper-type barns contains relatively low readily biodegradable organic. Therefore NOx-N was accumulated during repeating sub-cycle in SBR operation. When acetic acid was fed as ECS during the final sub-cycle, the maximum nitrogen removal rate was 0.22 kg N/m3/d. This was due to both less denitrification rate during the sub-cycle period and inhibition of denitrification by pH drop during the final cycle. The pH drop was caused by a large amount of ECS feeding to remove high concentration of NOx-N in the final period. To overcome these limitations and achieve higher nitrogen removal rate, the intermittent ECS feeding method with raw wastewater at every anoxic period was developed. Using the modifying ECS feeding method, the removal rate was increased to 0.45 kg N/m3/d without NOx-N accumulation.

Agriculture↗

Mutational analysis of forkhead transcriptional factor 2 (FOXL2) in Korean patients with blepharophimosis-ptosis-epicanthus inversus syndrome.

We screened for mutations in the forkhead transcription factor gene, FOXL2, in Korean patients with sporadic or familial blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) by polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) and direct sequencing. Five of nine BPES families and three of seven sporadic cases were detected to have FOXL2 mutations. We identified four types of FOXL2 mutations, two of which are novel. A new 14 bp deletion (939-952del14) causing a frameshift from G235W and the extension of the predicted protein to 527 amino acids was detected in a BPES family patient. In addition, a novel 845C > A transversion, resulting in a nonsense mutation (S203X), was found in a sporadic case of BPES. The previously reported in-frame 30 bp duplication (909-938dup30) was the most common mutation and was found in eight patients of four BPES families and one sporadic case. A known 17 bp duplication (1080-1096dup17) was observed in a sporadic BPES case. We were unable to find a causal mutation in four BPES families and four sporadic cases. These results suggest that in a fraction of BPES patients, the genetic defect might be associated with a mutation in the non-coding region of the FOXL2 gene or in other genes.

Adolescent↗

Chemically induced rat mammary tumor treated with tamoxifen showed decreased expression of cyclin D1, cyclin E, and p21(Cip1).

We studied the effects of tamoxifen (TAM) on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumor and the expression of cyclin D1, cyclin E, p21(Cip1), and estrogen receptors (ER) by performing immunohistochemistry and Western blot analysis. When tumor size reached between 10 and 15mm in the largest dimension, the rats were divided into a DMBA-control group and a DMBA-TAM group. The administration of TAM markedly decreased the tumor development and showed decreased expression of bromodeoxyuridine, cyclin D1, cyclin E, and p21(Cip1) when compared with those of the DMBA-control group; however, a few tumors showed progressive growth in spite of TAM treatment. These tumors had decreased expression of ER. This study suggests that TAM suppresses tumor development through the down-expression of cyclin D1 and cyclin E.

9,10-Dimethyl-1,2-benzanthracene↗

Self-assembled monolayer of a redox-active calix[4]arene: voltammetric recognition of the Ba2+ ion in aqueous media.

The Redox-active monolayer of a novel calix[4]arene recognizing redox-inactive ionic species by voltammetry is reported. Calix[4]arene-disulfide-diquinone, which is not only redox-active but is also a highly selective ionophore for the Ba2+ ion, spontaneously forms a stable and dense monolayer film on gold. The redox-active calixarene monolayer selectively recognizes Ba2+ ion in aqueous media, and the voltammetric signals are proportional to the ionic concentration. A new voltammetric peak can be detected by square-wave voltammetry upon adding a dilute solution containing Ba2+ ion having a concentration as low as 1.0 x 10(-6) M. The Langmuir plot (1/ip vs 1/[Ba2+]) shows a linear slope in the range from 1.0 x 10(-6) M to 1.0 x 10(-4) M. This modified electrode does not show any significant interference from alkali and alkaline earth metal ions except for Sr2+ and Ca2+. Only 100- and 500-fold concentrations of Sr2+ and Ca2+ ions, respectively, can lead to voltammetric responses comparable to that of Ba2+.

Journal Article↗

Anti-atherogenic effect of citrus flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP-1 in high cholesterol-fed rabbits.

The anti-atherogenic effects of the citrus flavonoids, naringin and naringenin, were evaluated in high cholesterol-fed rabbits. At 3 months of age, 30 male New Zealand White (NZW) rabbits were divided into three groups (n = 10 per group). The rabbits were fed a 1% cholesterol diet alone (control group) or a diet supplemented with either 0.1% naringin or 0.05% naringenin for 8 weeks. The plasma lipoprotein levels, total cholesterol, triglyceride, and high-density lipoprotein showed no significant differences in the control and experimental groups. Hepatic acyl-CoA:cholesterol acyltransferase (ACAT) activity was slightly low in naringin (5.0%)- and naringenin (15.0%)-fed rabbits, compared to control group. The aortic fatty streak areas were significantly lower in both the naringin (19.2 +/- 5.6%)- and naringenin (18.1 +/- 6.5%)-supplemented groups than in the control group (60.4 +/- 14.0%). The expression levels of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1), by semiquantitative RT-PCR analysis of the thoracic aorta, were significantly lower in the flavonoids supplemented groups than in the control group. These results suggest that the anti-atherogenic effect of the citrus flavonoids, naringin and naringenin, is involved with a decreased hepatic ACAT activity and with the downregulation of VCAM-1 and MCP-1 gene expression.

Actins↗

Effect of exercise intensity and frequency on lipid levels in men with coronary heart disease: Training Level Comparison Trial.

The objective of the Training Level Comparison Trial was to determine whether a more intense exercise program versus a less intensive program has additional favorable effects on blood lipids in men with coronary heart disease (CHD) over a 12-month period. The study-a randomized, controlled trial conducted at 2 clinical centers-enrolled 185 patients with documented CHD. A simple randomization procedure led to unequal numbers of patients in the 2 interventions: 82 in the low-intensity and 103 in the high-intensity group. Target heart rate during exercise corresponded to 50% of maximum oxygen uptake (VO(2 max)) +/- 5 beats/min in the low-intensity group and 85% +/- 5 beats/min in the high-intensity group. The intensity of exercise made little difference on lipid improvements. However, the attendance rates for the 6- and 12-month periods (percentage of total exercise sessions attended) were significantly related to increased high-density lipoprotein (HDL) cholesterol (r(s) [Spearman rank correlation coefficient 0.20 to 0.26, p <0.05]), and decreases in the ratios of low-density lipoprotein (LDL)-to-HDL cholesterol (LDL:HDL, r(s) = -0.24 to -0.28, p < 0.01) and total-to-HDL cholesterol (total:HDL, r(s) = -0.25 to -0.29, p < 0.01) at 6 and 12 months. The relation of the attendance rate to LDL:HDL and total:HDL ratios remained significant in repeated-measures regression analysis. Exercise frequency may be more important than intensity in improving HDL cholesterol and LDL:HDL and total:HDL ratios in men with CHD.

Adult↗

Group IIA secretory phospholipase A(2) stimulates inducible nitric oxide synthase expression via ERK and NF-kappaB in macrophages.

The mammalian group IIA secretory phospholipase A(2) (sPLA(2)) is believed to play an important role in inflammation and cell injury. The present study underlines the importance of group IIA sPLA(2) in the regulation of iNOS. Treatment of cells with sPLA(2) induced protein expression and mRNA accumulation of iNOS in a dose-dependent manner. The pretreatment of cells with rho-BPB or SCA, selective sPLA(2) inhibitors, inhibited sPLA(2)-induced iNOS expression. sPLA(2) stimulated the simultaneous activation of two classes of mitogen-activated protein kinases ERK and JNK, but did not stimulate p38 MAPK. PD98059, a selective MEK inhibitor, inhibited sPLA(2)-induced nitrite production and iNOS expression as well as ERK phosphorylation. In addition, pretreatment of rho-BPB or SCA also resulted in inhibition of sPLA(2)-induced ERK phosphorylation. The sPLA(2) signaling mechanisms involving the activation of transcription factor NF-kappaB were studied in the same cells. That stimulation of cells with sPLA(2) caused NF-kappaB activation in a time-dependent manner was shown by the detection of NF-kappaB-specific DNA-protein binding and by IkappaBalpha degradation. sPLA(2)-induced NF-kappaB activation was prevented in the presence of rho-BPB. Furthermore, the NF-kappaB inhibitor PDTC suppressed sPLA(2)-induced nitrite production and iNOS expression as well as IkappaBalpha degradation. The results strongly suggest that group IIA sPLA(2) induces iNOS in macrophages and that this induction occurs through ERK and NF-kappaB.

Animals↗

Case report: diabetic muscle infarction presenting as knee arthralgia.

Diabetic muscle infarction is a rare complication of diabetes and has characteristic clinical features including acute onset of pain with painful swelling, most commonly in the thigh or calf muscle, which gradually improves to complete resolution. Recently we experienced a case of diabetic muscular infarction presenting as knee joint pain due to involvement of the proximal portion of the leg muscle, which site has not been reported previously. This case shows that diabetic muscle infarction may involve sites other than the thigh and calf areas and should be considered in the differential diagnosis of knee arthralgia.

Aged↗