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Biomedical subjects

M Park

Publications and source records attributed to M Park.

At least 19 recordsLinked to original sources

Abdominal obesity, systolic blood pressure, and microalbuminuria in normotensive and euglycemic Korean men.

OBJECTIVES: To evaluate the relationship between abdominal obesity and microalbuminuria (MA) in normotensive, euglycemic Korean men. DESIGN: A cross-sectional study at a health screening center. SUBJECTS: A total of 1321 healthy, normotensive Korean men, aged 20-78 years, with a fasting plasma glucose level <100 mg/dl. MEASUREMENTS: Height, weight, and waist; systolic blood pressure (SBP); diastolic blood pressures (DBP); urinary albumin to creatinine ratio (ACR); fasting glucose, insulin, lipids, C-reactive protein (CRP), and white blood cell count. Waist circumference (WC) was used to indicate abdominal obesity and a single measurement of ACR was used to estimate MA. We also calculated body mass index (BMI) based on weight and height. RESULTS: Mean BMI, WC, and SBP were significantly higher in subjects with MA than in those without (24.8+/-4.1 vs 23.8+/-2.7 kg/m2, 86+/-9 vs 83+/-8 cm, and 115+/-5 vs 112+/-7 mmHg, respectively). Multiple logistic regression analyses showed that only WC and SBP were independent predictors of MA. CONCLUSION: WC and SBP were positively associated with MA in normotensive and euglycemic Korean men.

Abdominal Fat↗

Mefloquine induces dose-related neurological effects in a rat model.

Mefloquine is one of the drugs approved by the FDA for malaria chemoprophylaxis. Mefloquine is also approved for the treatment of malaria and is widely used for this purpose in combination with artesunate. However, the clinical utility of the compound has been compromised by reports of adverse neurological effects in some patients. In the present study, the potential neurological effects of mefloquine were investigated with six 7-week-old female rats given a single oral dose of the compound. Potential mefloquine-induced neurological effects were monitored using a standard functional observational battery, automated open field tests, automated spontaneous activity monitoring, a beam traverse task, and histopathology. Plasma mefloquine concentrations were determined 72 h after dosing by using liquid chromatography-mass spectrometry. Mefloquine induced dose-related changes in endpoints associated with spontaneous activity and impairment of motor function and caused degeneration of specific brain stem nuclei (nucleus gracilis). Increased spontaneous motor activity was observed only during the rats' normal sleeping phase, suggesting a correlate to mefloquine-induced sleep disorders. The threshold dose for many of these effects was 187 mg/kg of body weight. This dose yielded plasma mefloquine concentrations after 72 h that are similar to those observed in humans after the treatment dose. Collectively, these data suggest that there may be a biological basis for some of the clinical neurological effects associated with mefloquine.

Animals↗

Consumption of milk and calcium in midlife and the future risk of Parkinson disease.

OBJECTIVE: To examine the relation between milk and calcium intake in midlife and the risk of Parkinson disease (PD). METHODS: Findings are based on dietary intake observed from 1965 to 1968 in 7,504 men ages 45 to 68 in the Honolulu Heart Program. Men were followed for 30 years for incident PD. RESULTS: In the course of follow-up, 128 developed PD (7.1/10,000 person-years). Age-adjusted incidence of PD increased with milk intake from 6.9/10,000 person-years in men who consumed no milk to 14.9/10,000 person-years in men who consumed >16 oz/day (p = 0.017). After further adjustment for dietary and other factors, there was a 2.3-fold excess of PD (95% CI 1.3 to 4.1) in the highest intake group (>16 oz/day) vs those who consumed no milk. The effect of milk consumption on PD was also independent of the intake of calcium. Calcium from dairy and nondairy sources had no apparent relation with the risk of PD. CONCLUSIONS: Findings suggest that milk intake is associated with an increased risk of Parkinson disease. Whether observed effects are mediated through nutrients other than calcium or through neurotoxic contaminants warrants further study.

Age of Onset↗

The preoperative intraocular pressure level predicts the amount of underestimated intraocular pressure after LASIK for myopia.

AIMS: To evaluate the statistical significance of the parameters that affect underestimation of intraocular pressure (IOP) after laser in situ keratomileusis (LASIK) for myopia. METHODS: In this prospective case series study, patient age, axial length, preoperative corneal curvature, preoperative central corneal thickness (CCT), preoperative IOP, and ablation depth were studied to determine whether they affect the underestimation of IOP in the right eyes of 100 consecutive patients who underwent LASIK. RESULTS: The preoperative IOP was the most important parameter for an amount of underestimated Goldmann applanation tonometric IOP (GAT) and non-contact tonometric IOP (ncIOP) at 1 month (r = 0.654, p<0.0001, R(2) = 0.427, and r = 0.694, p<0.0001, R(2) = 0.481, respectively) and 3 months (r = 0.637, p<0.0001, R(2) = 0.406, and r = 0.726, p<0.0001, R(2) = 0.527, respectively). Patient age was statistically significant for underestimating the GAT at 1 month, and both the ablation depth and CCT were statistically significant parameters for underestimating the ncIOP at 1 month and at 3 months by stepwise multiple regression analysis (F>4.000). However, these parameters had small bivariate correlation coefficients, and were considered as minor parameters. CONCLUSION: Preoperative IOP is the most important parameter that affects an underestimation of IOP after LASIK for myopia. Eyes with a higher true IOP have a larger underestimation of the IOP after LASIK for myopia. From these results, the importance of the modulus of elasticity on IOP measurements was discussed.

Adult↗

Utility of digital photographs of the hand for assessing the presence of hand osteoarthritis.

OBJECTIVES: Nodal osteoarthritis of the hand (hand OA) is a subset of OA with a strong heritable component. Multiple genetic analyses of this condition have been performed and are underway. Highest yield from any genetic study depends upon a clear clinical phenotype for case definition. Radiographs may provide the most detail about the nature of the lesion. Physical examination is an imperfect means of evaluating each patient, particularly when hundreds or thousands of patients are required for study. Our study evaluated the accuracy, relative to a radiograph, of a digital photograph of the hands for the presence of OA in a particular joint, as well as for the diagnosis of nodal hand OA. METHODS: Consecutive patients were evaluated as part of the I-NODAL study (Investigation of Nodal Osteoarthritis to Detect an Association with Loci encoding Interleukin-1 [IL-1]). Evaluation included a physical examination by a trained rheumatologist, a postero-anterior radiograph of the hands, and a digital photograph of each hand. Radiographs were read by one trained observer using the Kellgren-Lawrence scale. Photographs were taken by one individual and were analyzed by an experienced rheumatologist. Kappa statistics were determined for each modality and accuracy was assessed using radiographic readings as a gold standard. RESULTS: Intra-reader reliability for radiograph interpretation was good for the overall diagnosis of hand OA (kappa0.76 [0.45,1.07]), but varied widely for the presence or absence of K-L grades 2-4 in individual joints (median kappa0.70, range 0.49-0.87 for ACR index joints). Distal interphalangeal joint (DIP) nodes on physical examination were sensitive (median 96.27, 93.94-100), but not specific for radiographic hand OA in the corresponding joint (median 33.0, 17.24-42.86). Physical examination evidence of OA in the 1st carpo-metacarpal (CMC) and proximal interphalangeal (PIP) joints provided only moderate sensitivity and specificity. However, the negative predictive value of the examination of individual joints was good (median negative predictive value was 82.58 for IP joints with a range 68.29-100.00), particularly in the DIP joints. Specificity of a node visualized on hand photograph was variable (median for all IP joints and 1st CMC 83.77, range 53.37-96.97), with greatest specificity for radiographic OA in the corresponding joint found in the 1st CMC and the PIP joints. Clinical hand OA was sensitive, but not specific for the radiographic diagnosis of hand OA; while, photographic OA was moderately specific, but insensitive. CONCLUSION: The visualization of a node on a digital photograph of the hand provides fair to moderate specificity for radiographic hand OA in the corresponding joint, with generally poor sensitivity. A photograph has limited value as a screening tool for the diagnosis of radiographic hand OA.

Aged↗

Antagonism of the acute hemodynamic effects of captopril in decompensated congestive heart failure by aspirin administration.

The concomitant use of angiotensin-converting enzyme inhibitors and aspirin may cause pharmacological antagonism. Hence we examined the effect of aspirin on the neurohormonal function and hemodynamic response to captopril in heart failure patients. Between April 1999 and August 2000, 40 patients were randomized into four equal groups: 1) captopril, 2) aspirin, 3) captopril-aspirin: captopril was given alone on the first day, followed by aspirin on the remaining days, and 4) aspirin-captopril: aspirin was given alone on the first day, followed by captopril on the remaining days. Hemodynamic, norepinephrine and prostaglandin measurements were performed pre- and post-medication for 4 days. Captopril (50 mg) was given orally every 8 h and 300 mg aspirin was given on the first day, and 100 mg/day thereafter. In the captopril group and only on the first day of captopril-aspirin, captopril produced increases in cardiac index (2.1 +/- 0.6 to 2.5 +/- 0.5 l min-1 m-2, P<0.0001), and reduced peripheral vascular resistance (1980 +/- 580 to 1545 +/- 506 dyn s-1 cm-5/m , P<0.0001) and pulmonary wedge pressure (20 +/- 4 to 15 +/- 4 mmHg, P<0.0001). In contrast, aspirin alone or associated with captopril showed no significant hemodynamic changes. Norepinephrine decreased (P<0.02) only in the captopril group. Prostaglandin levels did not differ significantly among groups. Thus, aspirin compromises the short-term hemodynamic and neurohormonal effects of captopril in patients with acute decompensated heart failure.

Aged↗

Residues in the C-terminal region of activin A determine specificity for follistatin and type II receptor binding.

Activin is a secreted growth factor that signals by binding two related classes of single transmembrane receptors at the cell surface. The interaction of activin with its receptors is highly regulated by other cell surface receptors, antagonistic ligands, and high affinity extracellular binding proteins such as follistatin. Two activin A mutants, the deletion mutant des[85-109]-activin A and the point mutant K102E-activin A (K102E), were investigated with respect to their ability to bind cell surface receptors and the binding protein follistatin. The deletion mutant exhibits low affinity for both receptors and follistatin whereas the point mutant fails to bind cell surface receptors but binds follistatin-288 with high affinity. K102E is able to compete with wild type activin to bind to follistatin and can thus increase the concentration of activin available for receptor binding and signaling. These findings underline the importance of the C-terminal region of activin for binding interactions and show that different residues in this region are involved in cell surface receptor and follistatin interactions.

Activins↗

Highly sensitive multiplex assay for detection of human immunodeficiency virus type 1 and hepatitis C virus RNA.

Various nucleic acid assays have been developed and implemented for diagnostics and therapeutic monitoring of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections. The high-throughput, semiautomated assays described here were developed to provide a method suitable for screening plasma specimens for the presence of HIV-1 and HCV RNAs. Three assays were developed: a multiplex HIV-1/HCV assay for simultaneous detection of HIV-1 and HCV, and discriminatory assays for specific detection of HIV-1 and HCV. The assay systems utilize three proprietary technologies: (i) target capture-based sample preparation, (ii) transcription-mediated amplification (TMA), and (iii) hybridization protection assay (HPA). An internal control is incorporated into each reaction to control for every step of the assay and identify random false-negative reactions. The assays demonstrated a sensitivity of at least 100 copies/ml for each target, and they detected with similar sensitivity all major variants of HCV and HIV-1, including HIV-1 group O strains. Assay sensitivity for one virus was not affected by the presence of the other. The specificity of these TMA-driven assays was >or=99.5% in both normal donor specimens and plasma containing potentially interfering substances or other blood-borne pathogens. Statistical receiver operating characteristic plots of 1 - specificity versus sensitivity data determined very wide analyte cutoff values for each assay at the point at which the assay specificity and sensitivity were both >or=99.5%. The sensitivity, specificity, and throughput capability predict that these assays will be valuable for large-volume plasma screening, either in a blood bank setting or in other diagnostic applications.

Blood Donors↗

Effects of ATP on TTX-sensitive and TTX-resistant sodium currents in rat sensory neurons.

Differential effects of ATP on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents in rat dorsal root ganglion neurons were studied using the whole-cell variation of path-clamp technique. Currents were evoked by step depolarizations to 0 mV from a holding potential of -80 mV. ATP suppressed TTX-S sodium currents while it increased TTX-R sodium currents. The effects were concentration-dependent and were reversible upon washout with ATP-free external solution. ATP-gamma-S, a hydrolysis-resistant ATP analog, also affected two types of sodium currents similarly to ATP, excluding the possibility that the effects were caused by the products of ATP hydrolysis, namely adenosine. ATP by modulating sodium currents may exert profound effects on the transmission of sensory information such as nociception.

Adenosine Triphosphate↗

Paternity determination when the alleged father's genotypes are unavailable.

In paternity testing using the DNA evidence, analysis of the deficiency case when the DNA profiles of the alleged father are not available is different from that of the case with complete evidence. In this paper, we describe how to evaluate and determine the paternity in the deficiency case, by comparing the paternity indexes of the true father and the falsely non-excluded man.

Chromosome Mapping↗

Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export.

RNA undergoing nuclear export first encounters the basket of the nuclear pore. Two basket proteins, Nup98 and Nup153, are essential for mRNA export, but their molecular partners within the pore are largely unknown. Because the mechanism of RNA export will be in question as long as significant vertebrate pore proteins remain undiscovered, we set out to find their partners. Fragments of Nup98 and Nup153 were used for pulldown experiments from Xenopus egg extracts, which contain abundant disassembled nuclear pores. Strikingly, Nup98 and Nup153 each bound the same four large proteins. Purification and sequence analysis revealed that two are the known vertebrate nucleoporins, Nup96 and Nup107, whereas two mapped to ORFs of unknown function. The genes encoding the novel proteins were cloned, and antibodies were produced. Immunofluorescence reveals them to be new nucleoporins, designated Nup160 and Nup133, which are accessible on the basket side of the pore. Nucleoporins Nup160, Nup133, Nup107, and Nup96 exist as a complex in Xenopus egg extracts and in assembled pores, now termed the Nup160 complex. Sec13 is prominent in Nup98 and Nup153 pulldowns, and we find it to be a member of the Nup160 complex. We have mapped the sites that are required for binding the Nup160 subcomplex, and have found that in Nup98, the binding site is used to tether Nup98 to the nucleus; in Nup153, the binding site targets Nup153 to the nuclear pore. With transfection and in vivo transport assays, we find that specific Nup160 and Nup133 fragments block poly[A]+ RNA export, but not protein import or export. These results demonstrate that two novel vertebrate nucleoporins, Nup160 and Nup133, not only interact with Nup98 and Nup153, but themselves play a role in mRNA export.

Active Transport, Cell Nucleus↗

DNA damage-dependent and -independent phosphorylation of the hRad9 checkpoint protein.

Cell cycle checkpoints are regulatory mechanisms that maintain genomic integrity by preventing cell cycle progression when genetic anomalies are present. The hRad9 protein is the human homologue of Schizosaccharomyces pombe Rad9, a checkpoint protein required for preventing the onset of mitosis if DNA damage is present or if DNA replication is incomplete. Genetic and biochemical analyses indicate that hRad9 is a component of the checkpoint response in humans and has possible roles in regulating the cell cycle, apoptosis, and DNA repair. Previous studies indicate that hRad9 is modified by phosphorylation, both in the absence of exogenous stress and in response to various genotoxins. In this study, we report the mapping of several sites of constitutive phosphorylation of hRad9 to (S/T)PX(R/P) sequences near the C terminus of the protein. We also demonstrate that a serine to alanine mutation at residue 272 abrogates an ionizing radiation (IR)-induced phosphorylation of hRad9 and further show that phosphorylation at (S/T)P sites is not a prerequisite for IR-induced phosphorylation of serine 272. Finally, we report that hRad9 undergoes cell cycle-regulated hyper-phosphorylation in G(2)/M that is enhanced by IR but distinct from that on serine 272. Unlike the IR-induced phosphorylation at serine 272, this event is dependent on serine 277 and threonine 292, two C-terminal (S/T)P sites in hRad9.

Cell Cycle↗

Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes.

Loss-of-function mutations in the cystatin B (Cstb) gene cause a neurological disorder known as Unverricht-Lundborg disease (EPM1) in human patients. Mice that lack Cstb provide a mammalian model for EPM1 by displaying progressive ataxia and myoclonic seizures. We analyzed RNAs from brains of Cstb-deficient mice by using modified differential display, oligonucleotide microarray hybridization and quantitative reverse transcriptase polymerase chain reaction to examine the molecular consequences of the lack of Cstb. We identified seven genes that have consistently increased transcript levels in neurological tissues from the knockout mice. These genes are cathepsin S, C1q B-chain of complement (C1qB), beta2-microglobulin, glial fibrillary acidic protein (Gfap), apolipoprotein D, fibronectin 1 and metallothionein II, which are expected to be involved in increased proteolysis, apoptosis and glial activation. The molecular changes in Cstb-deficient mice are consistent with the pathology found in the mouse model and may provide clues towards the identification of therapeutic points of intervention for EPM1 patients.

Animals↗

Phase transitions and critical phenomena in the liquid bridge under lateral acceleration.

We study the shape of a liquid body under the influence of a lateral body force in a thin liquid bridge. The shape of the liquid body changes continuously or discontinuously depending on the volume of liquid body. We show that the transition from discontinuous to continuous change is described by the volume-induced phase transition driven by the lateral body force. The order parameter of the phase transition is the amount of shift of the center of mass of liquid body. Critical exponents of a mean-field model have been obtained by numerical calculation. We provide the validity of this critical behavior through the m(4) model of Landau theory of phase transition.

Journal Article↗

Salt-thermal zeolitization of fly ash.

The molten-salt method has been recently proposed as a new approach to zeolitization of fly ash. Unlike the hydrothermal method, this method employs salt mixtures as the reaction medium without any addition of water. In this study, systematic investigation has been conducted on zeolitization of fly ash in a NaOH-NaNO3 system in order to elucidate the mechanism of zeolite formation and to achieve its optimization. Zeolitization of fly ash was conducted by thermally treating a powder mixture of fly ash, NaOH, and NaNO3. Zeolitization of fly ash took place above 200 degrees C, a temperature lower than the melting points of salt and base in the NaOH-NaNO3 system. However, it was uncertain whether the reactions took place in a local molten state or in a solid state. Therefore, the proposed method is renamed the "salt-thermal" method rather than the "molten-salt" method. Mainly because of difficulty in mobility of components in salt mixtures, zeolitization seems to occur within a local reaction system. In situ rearrangement of activated components seems to lead to zeolite formation. Particle growth, rather than crystal growth through agglomeration, resulted in no distinct morphologies of zeolite phases. Following are the optimal zeolitization conditions of the salt-thermal method: temperature, 250-350 degrees C; time, 3-12 h; weight ratio of NaOH/NaNO3, 0.3-0.5; weight ratio of NaNO3/fly ash, 0.7-1.4. Therefore, it is clear from this work that the salt-thermal method could be applied to massive zeolitization of fly ash as a new alternative method for recycling this waste.

Carcinogens↗

Absolute configuration, predominant conformations, and vibrational circular dichroism spectra of enantiomers of n-butyl tert-butyl sulfoxide.

Alkylation of the alpha-carbanion of (R)-(-)-tert-butyl methyl sulfoxide (4) with n-propyl bromide afforded (+)-n-butyl tert-butyl sulfoxide (1) to which the absolute configuration (R) was ascribed. This assignment was confirmed by X-ray analysis of the complex 6 obtained from the enantiomerically pure sulfoxide (-)-1 and mercury chloride. Vibrational absorption and circular dichroism spectra of (+)-1 were measured in CDCl3 solution in the 2000-900 cm(-1) region and compared with the ab initio predictions of absorption and VCD spectra obtained with density functional theory using the B3LYP/6-31G basis set for different conformers of (R)-1. This comparison indicated also that (+)-1 is of the (R)-configuration.

Journal Article↗