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Biomedical subjects

J Park

Publications and source records attributed to J Park.

At least 37 records · Page 2Linked to original sources
PubMed2005

Sirolimus inhibits platelet-derived growth factor-induced collagen synthesis in rat vascular smooth muscle cells.

Vascular smooth muscle cell (VSMC) proliferation and extracellular matrix (ECM) accumulation play key roles in the development and the progression of vascular remodeling such as transplant arteriosclerosis and restenosis. The present study examined the effects of sirolimus (SRL) on platelet-derived growth factor (PDGF)-induced fibronectin secretion, collagen synthesis, and the related signaling pathways including reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPK) in rat VSMCs. Primary rat VSMCs were isolated from male Sprague-Dawley rats. Growth arrested, synchronized cells were treated with various concentrations of SRL before the addition of PDGF at 10 ng/mL. Proliferating cell nuclear antigen expression, fibronectin secretion, and the activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK were assessed by Western blot analysis, collagen synthesis by [(3)H]-proline incorporation, and cellular ROS by flow cytometry. PDGF (10 ng/mL) increased VSMC proliferation by 1.7-fold, fibronectin secretion by 1.5-fold, collagen synthesis by 2.1-fold, cellular ROS by 1.6-fold, and activation of ERK and p38 MAPK by 3.3- and 3.9-fold compared to controls. SRL above 1 nmol/L inhibited PDGF-induced VSMC proliferation and collagen synthesis but not PDGF-induced fibronectin secretion, cellular ROS, and activation of ERK and p38 MAPK. These data demonstrated that PDGF increased ECM synthesis as well as proliferation through cellular ROS and subsequent MAPK activation and that SRL inhibited PDGF-induced VSMC proliferation and collagen synthesis in a cellular ROS- and MAPK activation-independent way.

Animals↗
PubMed2005

Vibration-assisted electron tunneling in C140 transistors.

We measure electron tunneling in transistors made from C(140), a molecule with a mass-spring-mass geometry chosen as a model system to study electron-vibration coupling. We observe vibration-assisted tunneling at an energy corresponding to the stretching mode of C(140). Molecular modeling provides explanations for why this mode couples more strongly to electron tunneling than to the other internal modes of the molecule. We make comparisons between the observed tunneling rates and those expected from the Franck-Condon model.

Carbon↗
PubMed2005

Screens using RNAi and cDNA expression as surrogates for genetics in mammalian tissue culture cells.

We have developed methods for the automation of transfection-grade DNA preparation, high-throughput retroviral preparation, and highly parallel phenotypic screens to establish approaches that will allow investigators to examine in an unbiased manner the roles of proteins in mammalian cells. These methods have been used to raise or lower the levels of individual kinases in individual micro-well cultures either by cDNA or short hairpin RNA expression and will allow investigators to treat mammalian cells in culture in manners that are analogous to genetic screens in yeast. Our proof-of-principle experiments have been performed in human cells using repositories that represent over 75% of the protein, nucleotide, carbohydrate, lipid, and amino acid kinases in the human genome. These initial experiments have demonstrated the feasibility of two general types of screens. We have performed phenotypic screens to identify proteins with specific roles in a chosen function and genetic interaction screens to establish epistatic relations between different proteins. The results suggest that any phenotype that can be scored by a robust assay in tissue culture is amenable to these types of screens and that interactions between mammalian proteins can be established. These results point to the near-term goal of establishing comprehensive, unbiased screens that will allow queries on the roles of all human proteins.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Growth substrate- and phase-specific expression of biphenyl, benzoate, and C1 metabolic pathways in Burkholderia xenovorans LB400.

Recent microarray experiments suggested that Burkholderia xenovorans LB400, a potent polychlorinated biphenyl (PCB)-degrading bacterium, utilizes up to three apparently redundant benzoate pathways and a C(1) metabolic pathway during biphenyl and benzoate metabolism. To better characterize the roles of these pathways, we performed quantitative proteome profiling of cells grown on succinate, benzoate, or biphenyl and harvested during either mid-logarithmic growth or the transition between the logarithmic and stationary growth phases. The Bph enzymes, catabolizing biphenyl, were approximately 16-fold more abundant in biphenyl- versus succinate-grown cells. Moreover, the upper and lower bph pathways were independently regulated. Expression of each benzoate pathway depended on growth substrate and phase. Proteins specifying catabolism via benzoate dihydroxylation and catechol ortho-cleavage (ben-cat pathway) were approximately an order of magnitude more abundant in benzoate- versus biphenyl-grown cells at the same growth phase. The chromosomal copy of the benzoyl-coenzyme A (CoA) (box(C)) pathway was also expressed during growth on biphenyl: Box(C) proteins were approximately twice as abundant as Ben and Cat proteins under these conditions. By contrast, proteins of the megaplasmid copy of the benzoyl-CoA (box(M)) pathway were only detected in transition-phase benzoate-grown cells. Other proteins detected at increased levels in benzoate- and biphenyl-grown cells included general stress response proteins potentially induced by reactive oxygen species formed during aerobic aromatic catabolism. Finally, C(1) metabolic enzymes were present in biphenyl-grown cells during transition phase. This study provides insights into the physiological roles and integration of apparently redundant catabolic pathways in large-genome bacteria and establishes a basis for investigating the PCB-degrading abilities of this strain.

Aerobiosis↗
PubMed2005

Virus removal in a pilot-scale 'advanced' pond system as indicated by somatic and F-RNA bacteriophages.

Advanced pond systems (APS), incorporating high-rate ponds, algal settling ponds, and maturation ponds, typically achieve better and more consistent disinfection as indicated by Escherichia coli than conventional waste stabilisation ponds. To see whether this superior disinfection extends also to enteric viruses, we studied the removal of somatic phages ('model' viruses) in a pilot-scale APS treating sewage. Measurements through the three aerobic stages of the APS showed fairly good removal of somatic phage in the summer months (2.2 log reduction), but much less effective removal in winter (0.45 log reduction), whereas E. coli was removed efficiently (> 4 logs) in both seasons. A very steep depth-gradient of sunlight inactivation of somatic phage in APS pond waters (confined in silica test tubes) is consistent with inactivation mainly by solar UVB wavelengths. Data for F-RNA phage suggests involvement of longer UV wavelengths. These findings imply that efficiency of virus removal in APS will vary seasonally with variation in solar UV radiation.

Disinfection↗
PubMed2005

Optical characteristics of waste stabilization ponds: recommendations for monitoring.

The optical character of waste stabilization ponds (WSPs) is of concern for several reasons. Algal photosynthesis, which produces oxygen for waste oxidation in WSPs, is influenced by attenuation of sunlight in ponds. Disinfection in WSPs is influenced by optical characteristics because solar UV exposure usually dominates inactivation. The optical nature of WSPs effluent also affects assimilation by receiving waters. Despite the importance of light behaviour in WSPs, few studies have been made of their optical characteristics. We discuss simple optical measures suitable for routine monitoring of WSPs (including at sites remote from laboratories): optical density of filtrates - an index of dissolved coloured organic (humic) matter, visual clarity - to provide an estimate of the beam attenuation coefficient (a fundamental quantity needed for optical modelling) colour (hue) - as an indicator of general WSP 'condition' and irradiance attenuation quantifying depth of light penetration. The value of optical characterisation of WSPs is illustrated with reference to optical data for WSPs in NZ (including high-rate algal ponds) treating dairy cattle wastewater versus domestic sewage. We encourage increased research on optical characteristics of WSPs and the incorporation of optical measures in monitoring and modelling of WSP performance.

Bioreactors↗
PubMed2004

Assessment of possible impact of a health promotion program in Korea from health risk trends in a longitudinally observed cohort.

BACKGROUND: Longitudinally observed cohort data can be utilized to assess the potential for health promotion and healthcare planning by comparing the estimated risk factor trends of non-intervened with that of intervened. The paper seeks (1) to estimate a natural transition (patterns of movement between states) of health risk state from a Korean cohort data using a Markov model, (2) to derive an effective and necessary health promotion strategy for the population, and (3) to project a possible impact of an intervention program on health status. METHODS: The observed transition of health risk states in a Korean employee cohort was utilized to estimate the natural flow of aggregated health risk states from eight health risk measures using Markov chain models. In addition, a reinforced transition was simulated, given that a health promotion program was implemented for the cohort, to project a possible impact on improvement of health status. An intervened risk transition was obtained based on age, gender, and baseline risk state, adjusted to match with the Korean cohort, from a simulated random sample of a US employee population, where a health intervention was in place. RESULTS: The estimated natural flow (non-intervened), following Markov chain order 2, showed a decrease in low risk state by 3.1 percentage points in the Korean population while the simulated reinforced transition (intervened) projected an increase in low risk state by 7.5 percentage points. Estimated transitions of risk states demonstrated the necessity of not only the risk reduction but also low risk maintenance. CONCLUSIONS: The frame work of Markov chain efficiently estimated the trend, and captured the tendency in the natural flow. Given only a minimally intense health promotion program, potential risk reduction and low risk maintenance was projected.

Journal Article↗
PubMed2004

Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis.

PURPOSE: We performed a phase I trial of intrathecal (IT) liposomal cytarabine (DepoCyt; Enzon Pharmaceuticals, Piscataway, NJ and SkyePharma Inc, San Diego, CA) to determine the maximum-tolerated dose, the dose-limiting toxicities, and the plasma and CSF pharmacokinetics of IT lipsomal cytarabine in children >/= 3 years of age with advanced meningeal malignancies. PATIENTS AND METHODS: Eighteen assessable patients received IT liposomal cytarabine through either an indwelling ventricular access device or via lumbar puncture. Liposomal cytarabine was given once every 2 weeks during induction, once every 4 weeks during consolidation, and once every 8 weeks during the maintenance phase of treatment. The initial dose was 25 mg, with subsequent escalations to 35 and 50 mg. CSF pharmacokinetic samples were obtained in a subset of patients. RESULTS: Arachnoiditis, characterized by fever, headache, nausea, vomiting, and back pain was noted in the first two patients at the 25 mg dose level. Therefore, subsequent patients were treated with dexamethasone, beginning the day of liposomal cytarabine administration and continuing for 5 days. Headache (grade 3) was dose limiting in two of eight patients enrolled at the 50 mg dose level. Eight of the 14 patients assessable for response demonstrated evidence of benefit manifest as prolonged disease stabilization or response. CONCLUSION: The maximum-tolerated dose and recommended phase II dose of liposomal cytarabine in patients between the ages of 3 and 21 years is 35 mg, administered with dexamethasone (0.15 mg/kg/dose, twice a day for 5 days). A phase II trial of IT liposomal cytarabine in children with CNS leukemia in second or higher relapse is in development.

Adolescent↗
PubMed2004

Combination chemotherapy with epirubicin, docetaxel and cisplatin (EDP) in metastatic or recurrent, unresectable gastric cancer.

Based on single agent activities and the additive or synergistic effects of three individual drugs in gastric cancer, we performed a phase II study of a new regimen combining epirubicin, docetaxel and cisplatin (EDP) for unresectable gastric cancer. The patients with histologically confirmed metastatic or recurrent, unresectable gastric cancer and no history of palliative chemotherapy were eligible for this trial. In total, 40 mg m(-2) epirubicin (reduced to 30 mg m(-2) due to high incidence of febrile neutropaenia; 75%) intravenously (i.v.) over 30 min, followed by 60 mg m(-2) docetaxel i.v. over 1 h, then 75 mg m(-2) cisplatin i.v. over 1 h was administered every 3 weeks. Between January 2002 and February 2003, 30 patients (epirubicin 40 mg m(-2), eight; 30 mg m(-2), 22) were enrolled. The median age was 52 years (range, 33-68). The patients received a median of four cycles (range, 1-8). One patient (3%) achieved a complete response, 13 (43%) showed partial responses, 13 (43%) had stable diseases and three (10%) progressed. The overall response rate was 47% (95% CI, 28-66%), and the median duration of response was 5.0 months (95% CI, 3.0-7.0). The median time to progression was 4.1 months (95% CI, 2.4-5.9), and the median overall survival was 11.0 months (95% CI, 9.5-12.4). Grade 4 neutropaenia were observed in 41%, and febrile neutropaenia in 32%, out of the patients receiving 30 mg m(-2) of epirubicin. Grade 3 nonhaematological toxicities included nausea, vomiting, anorexia and peripheral neuropathy. In conclusion, EDP is active in gastric cancer, with a manageable and predictable toxicity profile.

Adult↗
PubMed2004

Anterior interhemispheric approach for distal anterior cerebral artery aneurysm surgery: preoperative analysis of the venous anatomy can help to avoid venous infarction.

BACKGROUND: The anterior interhemispheric approach is a well-known operative technique for a distal anterior cerebral artery (ACA) aneurysm. However, a frontal parasagittal bridging vein is occasionally sacrificed in this approach, creating a risk of postoperative venous infarction. METHOD: To evaluate the risk of venous infarction, the current study investigated the venous phase of preoperative angiograms and postoperative CT scans for 20 patients in whom a parasagittal bridging vein had been sacrificed during the anterior interhemispheric approach. The draining territory index of the sacrificed bridging vein (DTISBV), draining territory index of the adjacent collateral ascending draining veins (DTIADV), and drainage impediment index (DII) were all calculated, plus the development of the superficial Sylvian vein (SSV) was evaluated. FINDINGS: Extensive postoperative venous infarction occurred in two of four patients with an aplastic SSV, for whom the DTISBVs were 41% and 43%, and the DIIs 26% and 37%. Among 16 patients with a normal SSV, two patients suffered postoperative venous congestion, and their DTISBVs were 40% and 50%, and their DIIs 21% and 30%. The other 14 patients without any postoperative venous drainage problems had a lower DTISBV and DII, where the DTISBV was 22.3+/-6.8% (mean+/-SD) and the DII 4.3+/-8.1%. CONCLUSIONS: The present results suggest that the venous phase of a preoperative angiogram should be carefully evaluated before distal ACA aneurysm surgery. In particular, a DTISBV and DII over 50% and 30%, respectively, in patients with a normal SSV and over 40% and 25%, respectively, in patients with an aplastic SSV were found to be critical to the production of postoperative venous infarction.

Aged↗
PubMed2004

Kinetics and mechanism of the C6H5 + CH3CHO reaction: experimental measurement and theoretical prediction of the reactivity toward four molecular sites.

The kinetics and mechanism of the reaction of C6H5 with CH3CHO have been investigated experimentally and theoretically. The total rate constant for the reaction has been measured by means of the cavity ring-down spectrometry (CRDS) in the temperature range 299-501 K at pressures covering 20-75 Torr. The overall bimolecular rate constant can be represented by the expression k = (2.8 +/- 0.2) x 10(11) exp[-(700 +/- 30)/T] cm3 mol-1 s-1, which is slightly faster than for the analogous C6H5 + CH2O reaction determined with the same method in the same temperature range. The reaction mechanism for the C6H5 + CH3CHO reaction was also explored with quantum-chemical calculations at various hybrid density functional theories (DFTs) and using ab initio high-level composite methods. The theories predict that the reaction may occur by two hydrogen-abstraction and two addition channels with the aldehydic hydrogen-abstraction reaction being dominant. The rate constant calculated by the transition state theory for the aldehydic hydrogen-abstraction reaction is in good agreement with the experimental result after a very small adjustment of the predicted reaction barrier (+0.3 kcal mol-1). Contributions from other product channels are negligible under our experimental conditions. For combustion applications, we have calculated the rate constants for key product channels in the temperature range of 298-2500 K under atmospheric-pressure conditions; they can be represented by the following expressions in units of cm 3mol-1 s-1: k1,cho = 8.8 x 10(3)T2.6 exp(-90/T), k2,ch3 = 6.0 x 10(1)T3.3 exp(-950/T), k3a(C6H5COCH3 + H) = 4.2 x 10(5)T0.6 exp(-410/T) and k3b(C6H5CHO + CH3) = 6.6 x 10(9)T-0.5 exp(-310/T).

Aldehydes↗
PubMed2004

Thermal decomposition of ethanol. III. A computational study of the kinetics and mechanism for the CH3+C2H5OH reaction.

The mechanism for the CH3+C2H5OH reaction has been investigated by the modified Gaussian-2 method based on the geometric parameters of the stationary points optimized at the B3LYP/6-311+G(d,p) level of theory. Five transition states have been identified for the production of CH4+CH3CHOH (TS1), CH4+CH3CH2O (TS2), CH4+CH2CH2OH (TS3), CH3OH+CH3CH2 (TS4), and CH3CH2OCH3+H (TS5) with the corresponding barriers 12.0, 13.2, 16.0, 44.7, and 49.9 kcal/mol, respectively. The predicted rate constants and branching ratios for the three lower-energy H-abstraction reactions were calculated using the conventional and variational transition state theory with quantum-mechanical tunneling corrections for the temperature range 300-3000 K. The predicted total rate constant, kt=8.36 x 10(-76) T(20.00) exp(5258/T) cm3 mol(-1) s(-1) (300-600 K) and 6.10 x 10(-25) T(4.10)exp(-4058/T) cm3 mol(-1) s(-1) (600-3000 K), agrees closely with existing experimental data in the temperature range 403-523 K. Similarly, the predicted rate constants for CH3+CH3CD2OH and CD3+C2H5OD are also in reasonable agreement with available low temperature kinetic data.

Journal Article↗
PubMed2004

Changes of pyridoxal kinase expression and activity in the gerbil hippocampus following transient forebrain ischemia.

In the previous study, we observed chronological alterations of glutamic acid decarboxylase (GAD), which is the enzyme converting glutamate into GABA. GAD isoforms (GAD65 and GAD67) differ substantially in their interactions with cofactor pyridoxal 5'-phosphate, which is catalyzed by pyridoxal kinase (PLK). In the present study, we examined the chronological changes of PLK expression and activity in the hippocampus after 5 min transient forebrain ischemia in gerbils. PLK immunoreactivity in the sham-operated group was detected weakly in the hippocampus. Ischemia-related change of PLK immunoreactivity in the hippocampus was significant in the hippocampal cornu ammonis (CA1)region, not in the hippocampal CA2/3 region and dentate gyrus. PLK immunoreactivity was observed in non-pyramidal GABAergic neurons at 30 min to 3 h after ischemic insult. At 12 h after ischemic insult, PLK immunoreactivity was shown in many CA1 pyramidal cells as well as some non-pyramidal cells. At this time point, PLK immunoreactivity and protein content was highest after ischemia. Thereafter, PLK immunoreactivity and protein content is decreased time-dependently by 4 days after ischemic insult. Four days after ischemia, some astrocytes expressed PLK in the CA1 region. The specific PLK activity was not altered following ischemic insult up to 2 days after ischemic insult. Thereafter, the specific PLK activity decreased time-dependently. However, total activity of PLK was significantly increased 12-24 h after ischemic insult, and thereafter total activity of PLK decreased. Therefore, we suggest that the over-expression of PLK in the CA1 pyramidal cells at 12 h after ischemia may induce increase of GAD in the CA1 pyramidal cells, which plays an important role in delayed neuronal death via the increase of GABA or enhancement of GABA shunt pathway.

Animals↗
PubMed2004

Stromal-epithelial measurements of prostate cancer in native Japanese and Japanese-American men.

We measured the histologic stromal and epithelial tissue components of the benign (normal) and malignant tissue compartments of Japanese-Americans (J-A) and native Japanese (NJ) men living in Japan. The patient cohort included 25 NJ men undergoing radical prostatectomy (RP) in Nagoya, Japan and 25 J-A (second or third generation US born). We conducted tissue image quantitation (in-house image software) of the stromal and epithelial compartments in malignant and adjacent normal tissue areas from a tissue microarray (TMA) selected from radical prostatectomy (RP) blocks. Stromal-epithelial (S-E) areas were determined using immunohistochemical stains for CAM-5.2 epithelial cytokeratin marker and the Masson trichrome stain to measure the stroma component. We observed differences in the volumes of normal and cancer epithelium and stroma within both the J-A and NJ study populations (P<0.01). Only the individual average cancer epithelium (CE) volume (JA=24.1 vs NJ=29.9) differed significantly between the NJ and J-A study populations (P=0.03). Consequently, the S-E ratio in NJ group was significantly different from that of J-A population (P=0.05). The decrease in S-E ratio noted in the malignant tissues of NJ prostate tissue may provide a biological marker for differentiation of the two groups and suggests a need for further investigations into the molecular basis for these histologic differences.

Aged↗
PubMed2004

Biphenyl and benzoate metabolism in a genomic context: outlining genome-wide metabolic networks in Burkholderia xenovorans LB400.

We designed and successfully implemented the use of in situ-synthesized 45-mer oligonucleotide DNA microarrays (XeoChips) for genome-wide expression profiling of Burkholderia xenovorans LB400, which is among the best aerobic polychlorinated biphenyl degraders known so far. We conducted differential gene expression profiling during exponential growth on succinate, benzoate, and biphenyl as sole carbon sources and investigated the transcriptome of early-stationary-phase cells grown on biphenyl. Based on these experiments, we outlined metabolic pathways and summarized other cellular functions in the organism relevant for biphenyl and benzoate degradation. All genes previously identified as being directly involved in biphenyl degradation were up-regulated when cells were grown on biphenyl compared to expression in succinate-grown cells. For benzoate degradation, however, genes for an aerobic coenzyme A activation pathway were up-regulated in biphenyl-grown cells, while the pathway for benzoate degradation via hydroxylation was up-regulated in benzoate-grown cells. The early-stationary-phase biphenyl-grown cells showed similar expression of biphenyl pathway genes, but a surprising up-regulation of C(1) metabolic pathway genes was observed. The microarray results were validated by quantitative reverse transcription PCR with a subset of genes of interest. The XeoChips showed a chip-to-chip variation of 13.9%, compared to the 21.6% variation for spotted oligonucleotide microarrays, which is less variation than that typically reported for PCR product microarrays.

Bacterial Proteins↗
PubMed2004

Capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer.

The selection of chemotherapeutic regimens is challenging for metastatic breast cancer (MBC) patients whose diseases have failed to respond to anthracyline and taxane. Capecitabine has advantages of oral administration and favorable toxicity profiles. This study was conducted to evaluate the efficacy of capecitabine and to identify the subgroup of patients who would potentially have benefit from capecitabine monotherapy in patients with anthracycline- and taxane-pretreated MBC. Female patients with MBC who had been previously treated with anthracycline and taxane received oral capecitabine 2500 mg/m(2) divided in two doses daily for 2 wk with 1-wk rest period. Between September, 1999, and December, 2002, a total of 38 patients were enrolled. Among the 36 evaluable patients, one patient achieved a complete response (CR), 9 patients had partial responses (PRs), and 13 patients had stable diseases (SDs). Response rate was 26% [95% confidence interval (CI), 12-40%] and the tumor control rate (TCR, CR+PR+SD) was 61% (95% CI, 45-77%). The median follow-up duration was 27.8 mo. The median duration of response was 8.9 mo, the median time to progression was 4.6 mo, and the median overall survival was 18.1 mo. The major toxicities were hand-foot syndrome, diarrhea, and emesis. There was no treatment-related death. The predictors of better overall survival were positivity of hormone receptor, disease-free survival longer than 1 yr, non-refractoriness to anthracycline, and fewer number (<or= 3) of involved organs. Capecitabine monotherapy is effective and well tolerated for MBC patients who had previously been treated with anthracycline and taxane. The TCR could predict overall survival as well as the objective response in this study, suggesting a possible role of TCR as a surrogate marker for survival in MBC patients on salvage chemotherapy. The patients who have relatively slow growing tumor and less tumor burden could have benefit from capecitabine monotherapy following anthracycline- and taxane-based chemotherapy.

Administration, Oral↗