Search PubMed⌕ Search

Biomedical subjects

J Park

Publications and source records attributed to J Park.

At least 217 records · Page 12Linked to original sources

Expression of peroxisomal proliferator-activated receptors and retinoid X receptors in the kidney.

The discovery that 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) is a ligand for the gamma-isoform of peroxisome proliferator-activated receptor (PPAR) suggests nuclear signaling by prostaglandins. Studies were undertaken to determine the nephron localization of PPAR isoforms and their heterodimer partners, retinoid X receptors (RXR), and to evaluate the function of this system in the kidney. PPARalpha mRNA, determined by RT-PCR, was found predominately in cortex and further localized to proximal convoluted tubule (PCT); PPARgamma was abundant in renal inner medulla, localized to inner medullary collecting duct (IMCD) and renal medullary interstitial cells (RMIC); PPARbeta, the ubiquitous form of PPAR, was abundant in all nephron segments examined. RXRalpha was localized to PCT and IMCD, whereas RXRbeta was expressed in almost all nephron segments examined. mRNA expression of acyl-CoA synthase (ACS), a known PPAR target gene, was stimulated in renal cortex of rats fed with fenofibrate, but the expression was not significantly altered in either cortex or inner medulla of rats fed with troglitazone. In cultured RMIC cells, both troglitazone and 15d-PGJ2 significantly inhibited cell proliferation and dramatically altered cell shape by induction of cell process formation. We conclude that PPAR and RXR isoforms are expressed in a nephron segment-specific manner, suggesting distinct functions, with PPARalpha being involved in energy metabolism through regulating ACS in PCT and with PPARgamma being involved in modulating RMIC growth and differentiation.

Adipose Tissue↗

Clinical economics in clinical trials: the measurement of cost and outcomes in the assessment of clinical services through clinical trials.

As the population ages and more expensive high-technology services become available, health care costs continue to spiral upward. Because the financial resources for health care are limited, economic analysis can help to evaluate expenditures and set priorities. Economic analysis of medical technology or medical care evaluates a medical service by comparing its dollar cost with its dollar benefit (cost-benefit), by measuring its dollar cost in relation to its outcomes (cost-effectiveness) as well as in relation to its utility or quality-adjusted outcomes (cost-utility), or simply by tabulating the costs involved (cost-identification). Direct costs are generated as services are provided. In addition, patients' productivity is affected, and these costs can be considered, especially in determining the benefit of a service that decreases morbidity or mortality. Intangible costs are those of pain, suffering, and grief. The point of view, or perspective, of the study determines the costs and benefits that will be measured in the analysis. Sensitivity analysis, which can evaluate the stability of the conclusions to the data used, is an important assessment within economic analysis. Economic analysis of new pharmaceutical therapies is increasingly being incorporated into clinical trials. Although there are some limitations of pharmacoeconomic information in clinical studies of drug safety and efficacy, these trials are often the only opportunity for economic data collection before adoption and reimbursement decisions are made. Validation after the drug has been introduced should complement economic information developed from clinical trials.

Clinical Trials as Topic↗

Special medical examination program reform proposal in Korea.

We are at a time when reform in the special medical examination program in keeping with the changing times is desperately needed because the common perception of workers, employers, and medical examination facilities is "special medical examination is merely ritualistic and unproductive." Therefore, we have tried to set forth the basic structure for reforming the special medical examination program by taking a close look at the management status of the current program and analyzing its problems. The specifics of the special medical examination program reform proposal consist of three parts such as the types, health evaluation based on occupational medicine, and the interval, subject selection, items and procedure. Pre-placement medical examination and non-periodic medical examinations-as-necessary are introduced newly. Health evaluation based on occupational medicine consists of classification of health status, evaluation of work suitability, and post-examination measure. Details regarding the medical examination interval, subject selection, items and procedure were changed.

Government↗

Omafilcon A (Proclear) soft contact lenses in a dry eye population.

PURPOSE: We conducted a 3-month, randomized, comparative cross-over study to evaluate the clinical performance of lenses manufactured from omafilcon A on subjects with signs and symptoms of dry eye. The subjects' own daily wear soft lenses were used as controls. METHODS: Seventy-six subjects with objective evidence of dry eye, as defined in the NEI/Industry Workshop Report 1995, were fit with either the omafilcon A lenses (Proclear) or new control lenses. Subjects wore the lenses for 6 weeks and then crossed over to bilateral wear of the other lenses for an additional 6 weeks. During each part of the study, we examined subjects at 1 week, 1 month, and 6 weeks. Signs and symptoms of dry eye were evaluated, and on-eye dehydration of the lens was assessed. RESULTS: When the subjects were wearing the omafilcon A lenses, there was a statistically significant improvement in a number of subjective parameters including comfort, dryness, frequency of eye irritation, and frequency of burning. We found significantly less on-eye dehydration of the lens and fluorescein corneal staining with the omafilcon A lenses. CONCLUSIONS: This study indicated that the daily wear of omafilcon A lenses provided better comfort, fewer symptoms, less on-eye dehydration, and less fluorescein corneal staining than other soft daily wear contact lenses in subjects with mild to moderate dry eye.

Adolescent↗

Usefulness of video-assisted thoracic surgery (Two Windows Method) in the treatment of lung cancer for elderly patients.

BACKGROUND: We have been performing it less invasively by making just two, small skin incisions (Two Windows Method) for lung cancer surgery. We assess the usefulness of VATS by the Two Windows Method in elderly patients. METHODS: The subjects were 32 of the 75-year-old or older patients with primary lung cancer in our department. We assessed cases in which thoracotomy was performed and the cases in which VATS by Two Windows Method was performed, and compared postoperative complications, hospital deaths, and postoperative length of stay. RESULTS: Operations by video-assisted thoracic surgery (VATS) by the Two Windows Method were completed in 20 of the 32 patients, and a conversion to thoracotomy was done in two patients (rate 9%). Ultimately, thoracotomy was performed in a total of 12 cases, including these two. In the thoracotomy patients, the most common postoperative complication was pneumonia/atelectasis (4 cases) secondary to poor sputum expectoration. There were 2 hospital deaths due to septicemia, and there was 1 due to pulmonary artery embolism. In the VATS patients, the rate of occurrence of postoperative complications was 30%, and clearly lower than the 67% among the thoracotomy patients (p<0.05). No hospital death occurred among the VATS patients. The postoperative hospital stay of the VATS patients (21 days) was shorter than that of the thoracotomy patients (31 days), (p<0.05). CONCLUSIONS: VATS by the Two Windows Method is safer than thoracotomy, and it should be considered first for lung cancer surgery in the aged.

Adenocarcinoma↗

Increase in signal intensities on T1-weighted magnetic resonance images in asymptomatic manganese-exposed workers.

OBJECTIVES: To clarify the clinical significance of increased signal intensities on T1 weighted magnetic resonance imaging (MRI) we performed a large-scale epidemiological study on asymptomatic manganese (Mn)-exposed workers with its focus on MRI. METHODS: We randomly selected 121 male workers out of a total of 750 workers including Mn-exposed, non-exposed manual, and non-exposed clerical workers in the factories. We studied environmental and biological monitoring, neurological examination, and MRI. RESULTS: The proportion of workers with increased signal intensities among the exposed, the non-exposed manual workers, and the non-exposed clerical workers was 46.1%, 18.8%, and 0%, respectively. Especially, 73.5% of the welders showed increased signal intensities. In no subject, were clinical signs of manganism observed. The pallidal index correlated with blood Mn concentration. CONCLUSION: Increase in signal intensities on the T1-weighted image reflect recent exposure to Mn, but not necessarily manganism. At which increase of signal intensity, the progression of manganism from Mn exposure occurs, remains to be solved.

Adult↗

A novel mutant loxP containing part of long terminal repeat of HIV-1 in spacer region: presentation of possible target site for antiviral strategy using site-specific recombinase.

A site-specific recombinase Cre is responsible for the recombination at a 34 bp loxP site. This system has been investigated for the antiviral strategy to excise proviral DNA from retrovirus-infected cells. It was reported that loxP sites could be inserted into long terminal repeat (LTR) of retrovirus to delete proviral DNA. To apply this system to human immunodeficiency virus type 1 (HIV-1) without inserting any DNA, one 34 bp sequence was selected from LTR of recombinant HIV-1 clone, loxLTR-1, based on sequence similarity between LTR and loxP, and sequence arrangement of 8 bp middle part in 34 bp LTR segment. When the 8 bp spacer region of loxP was changed into the corresponding middle part of loxLTR-1, this variant loxP would allow Cre to specifically recombine between themselves but not with wild-type loxP in vitro. This study suggests that site-specific excision of proviral DNA of HIV-1 could be catalyzed by the least modified Cre recognizing the loxLTR-1 sites.

HIV Infections↗

Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods.

The sequences of related proteins can diverge beyond the point where their relationship can be recognised by pairwise sequence comparisons. In attempts to overcome this limitation, methods have been developed that use as a query, not a single sequence, but sets of related sequences or a representation of the characteristics shared by related sequences. Here we describe an assessment of three of these methods: the SAM-T98 implementation of a hidden Markov model procedure; PSI-BLAST; and the intermediate sequence search (ISS) procedure. We determined the extent to which these procedures can detect evolutionary relationships between the members of the sequence database PDBD40-J. This database, derived from the structural classification of proteins (SCOP), contains the sequences of proteins of known structure whose sequence identities with each other are 40% or less. The evolutionary relationships that exist between those that have low sequence identities were found by the examination of their structural details and, in many cases, their functional features. For nine false positive predictions out of a possible 432,680, i.e. at a false positive rate of about 1/50,000, SAM-T98 found 35% of the true homologous relationships in PDBD40-J, whilst PSI-BLAST found 30% and ISS found 25%. Overall, this is about twice the number of PDBD40-J relations that can be detected by the pairwise comparison procedures FASTA (17%) and GAP-BLAST (15%). For distantly related sequences in PDBD40-J, those pairs whose sequence identity is less than 30%, SAM-T98 and PSI-BLAST detect three times the number of relationships found by the pairwise methods.

Databases, Factual↗

Structural assignments to the Mycoplasma genitalium proteins show extensive gene duplications and domain rearrangements.

The parasitic bacterium Mycoplasma genitalium has a small, reduced genome with close to a basic set of genes. As a first step toward determining the families of protein domains that form the products of these genes, we have used the multiple sequence programs PSI-BLAST and GEANFAMMER to match the sequences of the 467 gene products of M. genitalium to the sequences of the domains that form proteins of known structure [Protein Data Bank (PDB) sequences]. PDB sequences (274) match all of 106 M. genitalium sequences and some parts of another 85; thus, 41% of its total sequences are matched in all or part. The evolutionary relationships of the PDB domains that match M. genitalium are described in the structural classification of proteins (SCOP) database. Using this information, we show that the domains in the matched M. genitalium sequences come from 114 superfamilies and that 58% of them have arisen by gene duplication. This level of duplication is more than twice that found by using pairwise sequence comparisons. The PDB domain matches also describe the domain structure of the matched sequences: just over a quarter contain one domain and the rest have combinations of two or more domains.

Bacterial Proteins↗

Establishing a limit of recognition for a vapor sensor array.

Organic vapor analysis with microsensor arrays relies principally on two output parameters: the response pattern, which provides qualitative information, and the response sensitivity, which determines the limit of detection (LOD). The latter is used to define the operating limit in the low-concentration range, under the implicit assumption that, if a vapor can be detected, it can be identified and differentiated from other vapors on the basis of its response pattern. In this study, the performance of an array of four polymer-coated surface acoustic wave vapor sensors was explored using calibrated response data from 16 solvent vapors in Monte Carlo simulations coupled with pattern recognition analysis. The statistical modeling revealed that the ability to recognize a vapor from its response pattern decreases with decreasing vapor concentration, as expected, but also that the concentration at which errors in vapor recognition become excessive is well above the calculated LOD in most cases, despite the LOD being based on the least sensitive sensor in the array. These results suggest the adoption of a limit of recognition (LOR), defined as the concentration below which a vapor can no longer be reliably recognized from its response pattern, as an additional criterion for evaluating the performance of multisensor arrays. A generalized method for estimating the LOR is presented, as well as a means for improving the LOR via residual error analysis.

Calibration↗

Naphthoquinone analogs as inactivators of cdc25 phosphatase.

cdc25A and cdc25B were significantly overexpressed in certain types of cancers, and they represent potential therapeutic targets for anticancer drug. In this study, naphthoquinone analogs as cdc25A phosphatase inactivators were investigated.

Cell Cycle↗

Establishment and characterization of cell lines constitutively expressing hepatitis B virus X-protein.

We prepared human hepatoma cell lines, which expressed the human hepatitis B virus-X gene product. The plasmid pMAMneo-X, containing an HBV-X gene promoter, an enhancer and a structural gene was constructed. Transfected HBV-X gene integration and expression were detected by Southern and Northern blotting, as well as by chloramphenicol acetylase transferase (CAT) assay using various kinds of promoter-CAT reporter systems. HBV-X protein expression in stable transfectants was confirmed by immunofluorescence microscopy. Transfected cell lines showed permanent expression of HBV-X proteins. The HBV-X transfectant activated its target promoters in promoter-CAT constructs as reporters. The HBV-X transfectant enhanced AP-1 transcription factor binding to its target DNA. Therefore, X-transfectants are not only stable, but also have specific biological functions. Cell cycle analysis by flow cytometry showed that the majority of the transfectant cells are arrested in the G1 or G2 phase of the cell cycle. These cell lines may be useful in analyzing the biological functions of HBV-X and its functional role in the formation of hepatocellular carcinomas.

Carcinoma, Hepatocellular↗

Nuclear factor of activated T cells (NFAT) as a molecular target for 1alpha,25-dihydroxyvitamin D3-mediated effects.

The molecular basis of the immunomodulatory properties of 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) remains elusive. We demonstrate here that 1alpha,25(OH)2D3-mediated suppressive effects on the inducible expression of cytokine genes in human T cells may, in part, be due to diminished activity of the transcription factor NFAT. The vitamin D3 receptor (VDR) and its heterodimeric partner retinoid X receptor alpha (RXR alpha) specifically bound to the distal NFAT site in the human IL-2 promoter, and this binding was abolished by mutating unique regions in the NFAT oligonucleotide. In vitro inhibition of NFAT complex formation was noted when VDR-RXR alpha heterodimers were added to DNA binding reactions containing nuclear extracts from activated B or T cells, whereas in vitro NFkappaB complex formation was not significantly influenced. Furthermore, 1alpha,25(OH)2D3 treatment of activated T cells resulted in decreased formation of NFAT complexes detected upon incubation of nuclear extracts from these cells with 32P-labeled probe. Transient expression of both VDR and RXR alpha, but not of a single component, was capable of inhibiting expression of a NFAT-driven reporter gene in stimulated jurkat cells in a ligand-dependent manner. These results suggest that NFAT plays a crucial role in 1alpha,25(OH)2D3-mediated immunosuppressive activity.

Base Sequence↗

Regional vulnerability to endogenous and exogenous oxidative stress in organotypic hippocampal culture.

Organotypic cultures of the brain provide a unique opportunity to directly examine the regional vulnerability of specific brain regions like the hippocampus. Two well-characterized models of oxidative stress were used to examine the regional vulnerability of the hippocampus. Endogenous oxidative stress was induced by blocking synthesis of the endogenous antioxidant, glutathione with buthionine sulfoximine (BSO). Exogenous oxidative stress was induced with paraquat, an intracellular generator of superoxide. Injury was measured by quantitative fluorescence microscopy using the vital dye propidium iodide. BSO caused dose- and time-dependent injury that took at more than 24 h to develop. Injury began in discrete patches in the culture. In any given culture, each patch increased in size and intensity as incubation continued. The pattern was not clearly correlated with neuronal anatomy and may demonstrate glial vulnerability. Injury caused by BSO could be prevented with the antioxidants trolox or the 21-aminosteroid U-83836E, both of which are vitamin E derivatives. Paraquat also caused dose- and time-dependent injury, but the CA1 region of the hippocampus was most vulnerable. The same pattern of selective CA1 injury was caused by brief exposures to high concentrations and by prolonged exposures to much lower concentrations. Under some conditions, paraquat injury was prevented by iron chelation with deferoxamine or by blockade of either NMDA or AMPA/ kainate glutamate receptors. During paraquat exposure, glutathione concentration in the cultures was reduced prior to onset of propidium staining. The observation that the hippocampus has a similar selective regional pattern of vulnerability to paraquat and ischemia suggests that their mechanisms of injury may be related.

Animals↗