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Biomedical subjects

J Park

Publications and source records attributed to J Park.

At least 55 records · Page 3Linked to original sources

Application of a prediction model for identification of individuals at diabetic risk.

As a follow-up to our preceding paper, we attempted to extract features of health risk progression for diabetes in Sequential Multi Layered Perceptron (SMLP) via inverse processing of the learned structure. The time-varying risk progress was assessed with risk trajectory and conditional mixture model. Overall risk cut along with the prediction was stable over time and high body mass index (BMI) tops the health behavioral risks predicting the onset of diabetes. For the initial prediction, high BMI (obesity), high blood pressure (BP), high cholesterol, and diet in fatty food were significant. Over time, variations in trajectory were due to changes in BMI, stress, BP, cholesterol, and fatty food intake. We tested the effectiveness of identifying prediabetics by the SMLP by applying the implemented SMLP to a test population of employees from a large manufacturing company, where an early worksite health promotion was initiated (1984). This resulted in a potential sensitivity (71.4%) although there were issues like mapping corresponding risks and large time lags. A secondary test on the similar population as in the previous paper showed a promising sensitivity (86.5%) over 3 years. When combining with targeted screening such as impaired glucose tolerance test only for those predicted to be diabetics, the presented prediction model and extracted features can be used in implementing an effective disease prevention and management program.

Diabetes Mellitus, Type 2↗

Differential SPARC mRNA expression in Barrett's oesophagus.

Barrett's oesophagus (BE) is the precursor lesion to adenocarcinoma of the oesophagus. Understanding of the molecular alterations in this multistage process may contribute to improved diagnosis and treatment. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that modulates cell adhesion and growth. Alterations in SPARC expression have been observed in a variety of solid tumours. The aim of this study was to assess the prevalence and timing of SPARC mRNA expression in Barrett's multistage disease and to investigate the impact of SPARC alterations on the development and progression of this disease. SPARC mRNA expression was measured using a quantitative real-time RT-PCR method in 108 specimens from 19 patients with BE without carcinoma, 20 patients with Barrett's-associated adenocarcinoma (EA), and a control group (CG) of 10 patients without evidence of gastro-oesophageal reflux disease. The median SPARC mRNA expression was significantly upregulated in BE tissues compared to paired normal oesophagus (NE) tissues for the BE group (P=0.004) and for the EA group (P<0.001). The SPARC mRNA expression was significantly higher in adenocarcinoma of the oesophagus compared to matching NE tissue and compared to Barrett's tissues in the EA group (P<0.001). Furthermore, SPARC expression values were significantly different between metaplastic and dysplastic Barrett's tissues (P=0.014). In histologically normal squamous oesophagus tissues obtained from carcinoma patients (EA group), the SPARC mRNA expression was significantly higher compared to NE mucosa from the BE group and the CG group (P=0.03). These findings suggest that the upregulation of SPARC mRNA expression is an early event in the development and progression of BE and EA, and that high SPARC expression may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread 'field effect' is present in the NE of patients with oesophageal adenocarcinoma.

Adenocarcinoma↗

[In vitro effect of taurolidine on squamous cell carcinoma in the oral cavity].

Taurolidine (Taurolin) is a derivative of the amino acid taurine, successfully used in the treatment of peritonitis. In vitro and in vivo studies have shown that taurolidine inhibits cell proliferation and induces apoptosis in a variety of tumor cell lines. At present there are no published studies on the use of taurolidine in the treatment of squamous cell carcinoma. Our aim was to examine the inhibition of cell proliferation and induction of apoptosis in cell lines SCC 4 and SCC 15 treated with taurolidine in concentrations of 0.01%, 0.1%, and 0.5%. Analogue to the present investigations on adenocarcinoma cell lines, we used toxic antiseptic povidone iodine in the same concentration as for the reference group. Untreated cells were used as a control group. The cells were incubated with taurolidine or povidone iodine once for 2 h at 37 degrees C in 5% CO(2). Cell proliferation was assessed using WST-1 labeling kit after 3, 24, 48, 72, and 96 h. The additional measurement of cell apoptosis was examined using ELISA(PLUS) cell death detection kit and performed after 0, 24, and 48 h. The findings showed a significant inhibition of cell proliferation and induction of apoptosis in taurolidine-treated cells SCC 4 and SCC 15 in contrast to the reference group treated with povidone iodine or the untreated control group.

Antineoplastic Agents↗

Autologous peripheral blood stem cell transplantation with induction of autologous graft-versus-host disease in acute myeloid leukemia.

We studied whether the induction of autologous graft-versus-host disease (GVHD) has an antileukemic effect and consequently increases the survival of patients undergoing autologous peripheral blood stem cell transplantation (PBSCT). In all, 22 acute myeloid leukemia patients with favorable and intermediate cytogenetic risk, in their first complete remission, were administered cyclosporine c.i.v. from day 0 to day +28 at a dose of 3.0 mg/kg per day and interferon-gamma (IFN-gamma) at 0.025 mg/m(2) s.c. every other day from day +14 to day +42 following autologous PBSCT. Natural-killer (NK)-cell activity assays and skin biopsies were performed. Successful engraftment was achieved in all patients at a median of 13 days without significant additional toxicity. Histologically confirmed cutaneous GVHD developed in 12 patients, and NK-cell activity was significantly augmented after autologous PBSCT in those patients (P=0.03). After a median follow-up duration of 37.7 months (range, 7.3-72.8), the 3-year disease-free survival (DFS) and overall survival (OS) rates were 64.4 and 73.1%, respectively, without significant correlation with GVHD status or augmentation of NK-cell activity. These data suggest that the administration of cyclosporine and IFN-gamma following autologous PBSCT improves OS and DFS, which may be attributable to the antileukemic effect, although no difference in survival could be demonstrated between cutaneous GVHD-positive and -negative groups.

Acute Disease↗

Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: a comparison of adenoviral vectors and liposomes.

Large bone defects resulting from nonunion fractures or tumour resections are common clinical problems. Recent studies have shown bone morphogenetic protein-2 (BMP-2) gene transfer using adenoviral vectors to be a promising new therapeutic approach. However, comparative studies of different vectors are required to identify the optimal system for possible clinical trials. This study compares the use of liposome-mediated and adenoviral gene transfer for the generation of autologous BMP-2-producing bone marrow stromal cells (BMSC). Primary BMSC isolated from the rat femur were treated ex vivo with either an adenovirus or a liposome carrying human BMP-2 cDNA. The genetically modified cells were evaluated in vitro and transplanted into critical size defects in the rat mandible in vivo. BMSC treated with a reporter gene vector or untreated BMSC served as controls. The newly formed tissue was analysed by in situ hybridization, radiography and immunohistochemistry. Both groups of genetically modified cells produced BMP-2 for at least 2 weeks, and markers of new bone matrix such as osteopontin and osteocalcin were observed within 2 weeks following gene transfer. In the liposome group, the critical size defects were found completely healed at 6 weeks after the gene transfer, whereas the more efficient adenoviral gene transfer allowed for complete bone healing within 4 weeks. None of the three control groups showed bone healing, not even after 8 weeks. Thus, both liposome-mediated and adenoviral BMP-2 gene transfer to primary BMSC are suitable methods to achieve the healing of critical size bone defects in rats. As liposomes have proven sufficient for this purpose and offer several advantages over any other vector, such as ease of preparation, theoretically no limitation of the size of the DNA, and less immunological and safety problems, they may represent the best vector system for future clinical trials of bone regeneration by BMP-2 gene therapy.

Adenoviridae↗

Rhodococcus equi pneumonia in a heart transplant recipient in Korea, with emphasis on microbial diagnosis.

Rhodococcus equi is an opportunistic pathogen that usually causes infection in immunocompromised hosts. A heart transplant recipient who had been treated with amphotericin B for pulmonary aspergillosis showed newly developed multiple nodules with a central necrotic area in the right lower lobes. Cultures of several blood samples and an aspirate of the lung nodule yielded a Gram-positive coccobacillary bacterium, which was initially reported as a Corynebacterium species, but was later identified as R. equi by API CORYNE (bioMerieux SA, Marcy l'Etoile, France) and by demonstrating the production of 'equi factor'. The identification was subsequently confirmed by an R. equi-specific polymerase chain reaction (PCR). The patient was successfully treated with ciprofloxacin and azithromycin for 14 weeks. This is the first documented case of R. equi infection in Korea. There is a possibility of underestimation of R. equi infections due to the misidentification of the organism as a contaminating diphtheroid. Because R. equi will not respond to the conventional empirical therapy, the microbiology laboratory should identify R. equi in a timely manner. R. equi-specific PCR will be a useful confirmatory test in human infection.

Actinomycetales Infections↗

Impact of an interdisciplinary low vision service on the quality of life of low vision patients.

AIM: To investigate the impact of an interdisciplinary low vision service on the vision related quality of life of service users. METHODS: 71 patients were interviewed 2 weeks before their appointment with the service and again 6 months later to assess any changes in their vision related quality of life. The majority of these patients had age related macular degeneration. RESULTS: After contact with the service the majority of patients indicated a reduction in concern about most quality of life issues. They were significantly less anxious about deterioration of their vision, safety within the home, and coping with everyday life. CONCLUSION: Improvements in many areas of their vision related quality of life indicate that this interdisciplinary low vision service has a positive impact on the lives of service users. However many patients were still unable to carry out their preferred everyday activities, and feelings of loneliness and isolation were unchanged. The identification of issues unrelieved by input from the service will be important in planning future service delivery.

Activities of Daily Living↗

Photo-induced oxidation of a dinuclear Mn(2)(II,II) complex to the Mn(2)(III,IV) state by inter- and intramolecular electron transfer to Ru(III)tris-bipyridine.

To model the structural and functional parts of the water oxidizing complex in Photosystem II, a dimeric manganese(II,II) complex (1) was linked to a ruthenium(II)tris-bipyridine (Ru(II)(bpy)(3)) complex via a substituted L-tyrosine, to form the trinuclear complex 2 [J. Inorg. Biochem. 78 (2000) 15]. Flash photolysis of 1 and Ru(II)(bpy)(3) in aqueous solution, in the presence of an electron acceptor, resulted in the stepwise extraction of three electrons by Ru(III)(bpy)(3) from the Mn(2)(II,II) dimer, which then attained the Mn(2)(III,IV) oxidation state. In a similar experiment with compound 2, the dinuclear Mn complex reduced the photo-oxidized Ru moiety via intramolecular electron transfer on each photochemical event. From EPR it was seen that 2 also reached the Mn(2)(III,IV) state. Our data indicate that oxidation from the Mn(2)(II,II) state proceeds stepwise via intermediate formation of Mn(2)(II,III) and Mn(2)(III,III). In the presence of water, cyclic voltammetry showed an additional anodic peak beyond Mn(2)(II,III/III,III) oxidation which was significantly lower than in neat acetonitrile. Assuming that this peak is due to oxidation to Mn(2)(III,IV), this suggests that water is essential for the formation of the Mn(2)(III,IV) oxidation state. Compound 2 is a structural mimic of the water oxidizing complex, in that it links a Mn complex via a tyrosine to a highly oxidizing photosensitizer. Complex 2 also mimics mechanistic aspects of Photosystem II, in that the electron transfer to the photosensitizer is fast and results in several electron extractions from the Mn moiety.

2,2'-Dipyridyl↗

Isolated extramedullary relapse in the pleural fluid of a patient with acute myeloid leukemia following allogeneic BMT.

We report an unusual case of AML, in which the patient showed extramedullary relapse in the pleural fluid and the skin without bone marrow recurrence even 3 years after allogeneic BMT. On examination of the pleural effusion and the skin, which relapsed 31 months and 40 months, respectively, after BMT, we found that most of cells were as the XY-type recipient by quantitative X/Y FISH (fluorescence in situ hybridization). However, 100% of the bone marrow cells remained XX-type donor cells. In the present case, we believe that the graft-versus-leukemia (GVL) response in the extramedullary site was not so effective as that in the bone marrow, where it remains effective.

Acute Disease↗

The nomographic design approach to recycled water reatment by the nitritation process.

The side-stream generated recycled water in the wastewater treatment plants is characterized as high in both nitrogen concentration and fluctuation of load. Thus, the design approach for recycle water management became an important part of the biological nutrient removal system design. The application of nitrogen removal from recycled water using the nitritation process has recently been increased due to economical reasons associated with an effective carbon allocation as well as the minimization of aeration cost. The concept of nitritation reactor design related to an inhibition of nitrite oxidizer has not been fully practiced in reality because of the limited field experiences. In this paper, a new approach has been proposed to determine reactor size and oxygen requirement in nitritation process design. The SRT-based design approach has been examined based on a series of laboratory experiments.

Bioreactors↗

Simultaneous removal of cadmium and turbidity in contaminated soil-washing water by DAF and electroflotation.

The removal of cadmium and turbidity from contaminated soil-washing water was studied by dissolved air flotation (DAF) and electroflotation at laboratory scale by using sodium lauryl sulfate (SLS) as an anionic surfactant, and calcium hydroxide (Ca(OH)2) as a coagulant. Using DAF, and in the presence of SLS or Ca(OH)2, the maximum recovery rate of cadmium obtained at a stoichiometric cadmium to collector and coagulant ratio of 1:4.5 was 51.1% and 80.8%, while the removal rate of turbidity was 18.4% and 19.2%. However, satisfactory cadmium and turbidity removal was not obtained by DAF. Much more significant removal of cadmium (100%, not detected in the residual) and turbidity (95.7%) was obtained by electroflotation using an aluminium metal plate as electrode, which generated hydroxide and aluminum ion. As a consequence, electroflotation is considered an effective method to separate cadmium and turbidity from contaminated soil-washing water. The electroflotation process may have practical applications for the removal of other hazardous metals from contaminated soil-washing water.

Air↗

Synthesis of highly crystalline and monodisperse maghemite nanocrystallites without a size-selection process.

The synthesis of highly crystalline and monodisperse gamma-Fe(2)O(3) nanocrystallites is reported. High-temperature (300 degrees C) aging of iron-oleic acid metal complex, which was prepared by the thermal decomposition of iron pentacarbonyl in the presence of oleic acid at 100 degrees C, was found to generate monodisperse iron nanoparticles. The resulting iron nanoparticles were transformed to monodisperse gamma-Fe(2)O(3) nanocrystallites by controlled oxidation by using trimethylamine oxide as a mild oxidant. Particle size can be varied from 4 to 16 nm by controlling the experimental parameters. Transmission electron microscopic images of the particles showed 2-dimensional and 3-dimensional assembly of particles, demonstrating the uniformity of these nanoparticles. Electron diffraction, X-ray diffraction, and high-resolution transmission electron microscopic (TEM) images of the nanoparticles showed the highly crystalline nature of the gamma-Fe(2)O(3) structures. Monodisperse gamma-Fe(2)O(3) nanocrystallites with a particle size of 13 nm also can be generated from the direct oxidation of iron pentacarbonyl in the presence of oleic acid with trimethylamine oxide as an oxidant.

Journal Article↗

The green tea polyphenol (-)-epigallocatechin gallate attenuates beta-amyloid-induced neurotoxicity in cultured hippocampal neurons.

Previous evidence has indicated that the neuronal toxicity of amyloid beta (betaA) protein is mediated through oxygen free radicals and can be attenuated by antioxidants and free radical scavengers. Recent studies have shown that green tea polyphenols reduced free radical-induced lipid peroxidation. The purpose of this study was to investigate whether (-)-epigallocatechin gallate (EGCG) would prevent or reduce the death of cultured hippocampal neuronal cells exposed to betaA because EGCG has a potent antioxidant property as a green tea polyphenol. Following exposure of the hippocampal neuronal cells to betaA for 48 hours, a marked hippocampal neuronal injuries and increases in malondialdehyde (MDA) level and caspase activity were observed. Co-treatment of cells with EGCG to betaA exposure elevated the cell survival and decreased the levels of MDA and caspase activity. Proapoptotic (p53 and Bax), Bcl-XL and cyclooxygenase (COX) proteins have been implicated in betaA-induced neuronal death. However, in this study the protective effects of EGCG seem to be independent of the regulation of p53, Bax, Bcl-XL and COX proteins. Taken together, the results suggest that EGCG has protective effects against betaA-induced neuronal apoptosis through scavenging reactive oxygen species, which may be beneficial for the prevention of Alzheimer's disease.

Amyloid beta-Peptides↗

Transduction of human catalase mediated by an HIV-1 TAT protein basic domain and arginine-rich peptides into mammalian cells.

Antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) have been considered to have a beneficial effect against various diseases mediated by reactive oxygen species (ROS). Although a variety of modified recombinant antioxidant enzymes have been generated to protect against the oxidative stresses, the lack of their transduction ability into cells resulted in limited ability to detoxify intracellular ROS. To render the catalase enzyme capable of detoxifying intracellular ROS when added extracellularly, cell-permeable recombinant catalase proteins were generated. A human liver catalase gene was cloned and fused with a gene fragment encoding the HIV-1 Tat protein transduction domain (RKKRRQRRR) and arginine-rich peptides (RRRRRRRRR) in a bacterial expression vector to produce genetic in-frame Tat-CAT and 9Arg-CAT fusion proteins, respectively. The expressed and purified fusion proteins can be transduced into mammalian cells (HeLa and PC12 cells) in a time- and dose-dependent manner when added exogenously in culture medium, and transduced fusion proteins were enzymatically active and stable for 60 h. When exposed to H(2)O(2), the viability of HeLa cells transduced with Tat-CAT or 9Arg-CAT fusion proteins was significantly increased. In combination with transduced SOD, transduced catalase also resulted in a cooperative increase in cell viability when the cells were treated with paraquat, an intracellular antioxide anion generator. We then evaluated the ability of the catalase fusion proteins to transduce into animal skin. This analysis showed that Tat-CAT and 9Arg-CAT fusion proteins efficiently penetrated the epidermis as well as the dermis of the subcutaneous layer when sprayed on animal skin, as judged by immunohistochemistry and specific enzyme activities. These results suggest that Tat-CAT and 9Arg-CAT fusion proteins can be used in protein therapy for various disorders related to this antioxidant enzyme.

Amino Acid Sequence↗

Efficient intracellular delivery of an exogenous protein GFP with genetically fused basic oligopeptides.

Several oligopeptides, derived from certain proteins, translocate as a form fused to small molecules or exogenous proteins across the plasma membrane into cells. Some of these oligopeptides, the so-called protein-transduction domains (PTDs), contain a high proportion of basic residues. The translocation of some of these basic PTDs, such as oligoarginines, has been studied as chemically fused forms to other organic compounds. In this study, we also tested to determine whether or not oligoarginines, when fused genetically to an exogenous protein such as GFP, are also able to translocate efficiently across the plasma membrane. The oligoarginine Rn (n = 5,6,7,8,9)-GFP fusion proteins were translocated quite efficiently, and the transduction efficiency increased in proportion to the number of arginine residues. However, the cellular uptake of the oligolysine-GFP fusion proteins was less efficient than that of the corresponding oligoarginine-GFP fusion proteins. When fused to GFP, the translocation efficiency of R5 was similar to that of Tat(49-57)(RKKRRQRRR). This finding suggests that the arginine homo-oligopeptide is more efficient than other PTDs which contain a mixture of basic residues. On the other hand, both the K9- and Tat(49-57)-GFP fusion proteins were transduced with similar efficiencies. It appears that basic oligopeptides may be useful for the efficient translocation of diverse exogenous proteins as genetically fused forms.

Amino Acid Sequence↗

Nucleotide requirements for CDX2 binding to the cis promoter element mediating intestine-specific expression of guanylyl cyclase C.

Guanylyl cyclase C (GC-C), specifically expressed by intestinal epithelial cells, is the receptor for the Escherichia coli heat-stable enterotoxin that causes diarrhea. Tissue-specific expression of GC-C is mediated by the intestinal transcriptional regulator CDX2. This trans-activating protein regulates intestine-specific expression by binding to a critical sequence in the proximal promoter of GC-C. The precise nucleotide elements mediating CDX2 binding to promoter elements remain undefined. Several nuclear proteins form complexes with a DNA probe containing the promoter element of GC-C mediating CDX2 binding. The present study examined the nucleotide requirements in the consensus binding site and flanking regions in the cis element that mediates specific CDX2 binding to the promoter of GC-C. These studies identified seven core base pairs in the critical promoter element mediating tissue-specific expression of GC-C that are required for CDX2 binding. In addition, base pairs flanking this core sequence contribute to and are required for CDX2 recognition. These studies describe the precise nucleotide sequence within the GC-C promoter that comprises the CDX2 binding site required for intestine-specific expression.

3' Flanking Region↗

Ectopic expression of guanylyl cyclase C in CD34+ progenitor cells in peripheral blood.

PURPOSE: To examine the utility of guanylyl cyclase C (GC-C)-specific nested reverse transcriptase polymerase chain reaction (RT-PCR) to detect circulating tumor cells in patients with colorectal cancer. PATIENTS AND METHODS: Peripheral-blood mononuclear cells from 24 patients with Dukes' stage D colorectal cancer were analyzed by GC-C-specific nested RT-PCR using 1 microg of total RNA. Peripheral-blood mononuclear cells from 20 healthy volunteers served as controls. Additionally, peripheral-blood CD34+ progenitor cells were assayed for the expression of both GC-C and other epithelial cell-specific markers. RESULTS: GC-C mRNA was detected in blood mononuclear cells from all 24 patients with colorectal cancer and all healthy volunteers. These unexpected positive results reflected low-level ectopic transcription of GC-C in CD34+ progenitor cells. Moreover, CD34+ progenitor cells expressed other epithelial cell-specific markers, including prostate-specific antigen, prostate-specific membrane antigen, carcinoembryonic antigen, CK-19, CK-20, mucin 1, and GA733.2. Limiting the quantity of mononuclear cell total RNA analyzed to < or = 0.8 microg eliminated detection of GC-C and other tissue-specific transcripts in blood of healthy volunteers. However, under the same conditions, GC-C mRNA was detected in mononuclear cells from all 24 patients with metastatic colorectal cancer. Using 0.5 microg of total RNA and GC-C-specific primers, nested RT-PCR detected a single human colon carcinoma cell (approximately 20 to 200 GC-C transcripts/cell) in 10(6) to 10(7) mononuclear blood cells. CONCLUSION: These data suggest that GC-C may be useful for detecting circulating colorectal cancer cells. They also demonstrate that CD34+ cells are a source of ectopically expressed epithelial cell-specific markers and that CD34+ cells may contribute to the high false-positive rate generally observed when those markers are used to detect rare circulating metastatic cancer cells by RT-PCR.

Adult↗