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Biomedical subjects

S Park

Publications and source records attributed to S Park.

At least 19 recordsLinked to original sources

Cerebellar peduncular myelinolysis in a patient receiving hemodialysis.

Here, we report the observation of extrapontine lesions, in addition to the pontine lesions previously documented in a diagnosed case of hemodialysis-associated osmotic demyelination syndrome due to end-stage renal disease. The patient exhibited lesions on bilateral middle cerebellar peduncles, and had been receiving regular hemodialysis as treatment for end-stage renal disease. He presented with progressive gait disturbance and postural instability. Accompanying symptoms included peduncular hallucinations and mild cognitive dysfunction. Brain MRI revealed high signal intensity in the area of bilateral cerebellar peduncles on the diffusion and T2-weighted images, with a decreased signal intensity noted on the ADC map. The ataxic form of osmotic myelinolysis syndrome is quite rare. The involvement of the cerebellar peduncles in extrapontine myelinolysis in a patient with end stage renal disease has not, to our knowledge, been previously reported. Here, we describe the MRI findings and clinical features associated with this unique case, and include a review of the relevant literature.

Aged↗

Aminoglycoside-induced translational read-through in disease: overcoming nonsense mutations by pharmacogenetic therapy.

A third of inherited diseases result from premature termination codon mutations. Aminoglycosides have emerged as vanguard pharmacogenetic agents in treating human genetic disorders due to their unique ability to suppress gene translation termination induced by nonsense mutations. In preclinical and pilot clinical studies, this therapeutic approach shows promise in phenotype correction by promoting otherwise defective protein synthesis. The challenge ahead is to maximize efficacy while preventing interaction with normal protein production and function.

Aminoglycosides↗

Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer.

Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m-2 was administered on days 1 and 8 and cisplatin 60 mg m-2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0-82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer.

Aged↗

Changes in the levels of interferon-gamma and transforming growth factor-beta influence bronchial stenosis during the treatment of endobronchial tuberculosis.

BACKGROUND: Endobronchial tuberculosis (EBTB) has been shown to frequently complicate bronchial stenosis, a condition which can induce dyspnea as a result of airway obstruction, and is also frequently misdiagnosed as either bronchial asthma or lung cancer. OBJECTIVES: This study attempted to determine whether there was a correlation between interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) levels in the serum and bronchial washing fluid (BWF), and the results of the treatment of EBTB patients. METHODS: Thirty patients, all of whom were diagnosed as EBTB, were enrolled, as were 10 healthy control subjects. IFN-gamma and TGF-beta levels were measured by the ELISA method in the serum and BWF of these 30 EBTB patients before and after treatment. The EBTB patients were divided into two groups: those who exhibited bronchial stenosis after treatment and those who did not. Chest computed tomography (CT) and pulmonary function test (PFT) were performed in 16 and 25 patients, respectively, at initial bronchoscopy. RESULTS: IFN-gamma and TGF-beta levels in the BWF of the EBTB patients were elevated compared to the controls (p < 0.05). After 2 months of treatment, 13 of the 30 EBTB patients exhibited bronchial fibrostenosis and the other 17 cases had recovered without sequelae. In the bronchial stenosis group, the initial serum TGF-beta levels were lower than in the patients without bronchial stenosis (p < 0.05). Moreover, the levels of serum TGF-beta after treatment were shown to have decreased more than in the patients without bronchial stenosis (p < 0.05). On chest CT findings of 16 EBTB patients, bronchial narrowing was suspected except in 2 cases (1 edematous-hyperemic type, 1 actively caseating type of segmental bronchus). The common features of PFT in EBTB at the initial diagnosis were a restrictive pattern and normal ventilatory function. CONCLUSIONS: Elevated IFN-gamma and TGF-beta levels in the BWF of the EBTB patients may be related to EBTB pathogenesis. Lowered initial serum TGF-beta levels as well as the observed changes in the levels of TGF-beta in the serum after treatment have been implicated in bronchial fibrostenosis during the course of the disease.

Adult↗

Specific absorbed fraction for Korean adult voxel phantom from internal photon source.

Absorbed fraction (AF) and specific absorbed fraction (SAF) are crucial values for the calculation of radionuclide S-values and consequently for internal dose estimates. The formalism of the Medical Internal Radiation Dose (MIRD) committee of the Society of Nuclear Medicine (SNM) has been utilised as a standard in the calculation of individual organ doses for biologically distributed radionuclides and for different types of radiation. Although those quantities are highly sensitive to individual anatomical difference, the SAF dataset calculated by Caucasian-based stylised phantoms have been applied to Korean population until now. This study was intended to calculate the SAFs by using realistic Korean voxel phantom and Monte Carlo transport technique for the first time and compare the results with those of the existing Caucasian-based data and the Korean stylised phantom published recently. The up-to-date realistic Korean voxel phantom, KTMAN-2, which was developed from computed tomography (CT) images of an average Korean adult male, was employed for Monte Carlo calculation using EGSnrc user-code, developed for the purpose of this study. The SAFs for 32 target organs and tissues from the photon source, uniformly deposited in a total of 37 source organs and tissues, were calculated from KTMAN-2. The results were compared with those for an adult phantom of Oak Ridge National Laboratory (ORNL) and Korean adult stylised phantom. Two major reasons of discrepancy were analysed: (1) racial difference between the Korean and the Caucasian and (2) anatomical difference between stylised and voxel phantoms. When the source organ was identical to the target organ, difference in SAF caused by the difference in target-organ mass between the Korean and the Caucasian phantoms was mainly observed. When the source and target organs were not identical, significant difference in SAF was observed which was mainly attributed to the difference in inter-organ distance and organ shape between voxel and stylised phantoms.

Body Burden↗

Relationship of bone health to yearlong physical activity in older Japanese adults: cross-sectional data from the Nakanojo Study.

INTRODUCTION: We determined associations between bone health and the quantity and quality of habitual physical activity in a cohort of 172 free-living Japanese aged 65-83 years (76 men, 96 women). METHODS: The number of steps taken and the intensity of physical activity were measured every 4 s throughout each 24-h period for 1 year, using a specially adapted accelerometer that distinguished up to 11 levels of physical activity (expressed in metabolic equivalents, METs). At the end of the year, a quantitative ultrasonic technique assessed each participant's osteosonic index (OSI, reflecting bone stiffness in the calcaneus). RESULTS: The data were significantly described by linear and exponential regression models which showed that in both sexes the OSI score increased with increasing daily physical activity, up to the observed maximum values of approximately 14,000 steps/day and 50 min/day at an intensity >3 METs. However, when data were categorized into quartiles of physical activity, OSI scores were not significantly greater in persons exceeding recommended minimum standards of habitual physical activity (corresponding to counts of around 6,900 and 6,800 steps/day and durations >3 METs of around 18 and 16 min/day in men and women, respectively). All who met such criteria (with the exception of a few women) had OSI scores above the threshold for a clinical diagnosis of osteoporosis. Multivariate-adjusted logistic regression analyses predicted that men and especially women who engaged in <6,800 steps/day and <16 min/day of moderate-intensity physical activity were, respectively, 4.9-8.4 and 2.2-3.5 times more likely to sustain fractures than those participating in >8,200 steps/day and >25 min/day of activity >3 METs. CONCLUSION: Causation cannot be inferred from a cross-sectional study. Nevertheless, we suggest that from the viewpoint of bone health, elderly people should be encouraged to engage in low- and moderate-intensity habitual physical activity, taking >7,000 steps/day with a duration >15 min/day at >3 METs.

Aged↗

Enhanced Cd2+ -selective root-tonoplast-transport in tobaccos expressing Arabidopsis cation exchangers.

Several Arabidopsis CAtion eXchangers (CAXs) encode tonoplast-localized transporters that appear to be major contributors to vacuolar accumulation/sequestration of cadmium (Cd(2+)), an undesirable pollutant ion that occurs in man largely as a result of dietary consumption of aerial tissues of food plants. But, ion-selectivity of individual CAX transporter types remains largely unknown. Here, we transformed Nicotiana tabacum with several CAX genes driven by the Cauliflower Mosaic Virus (CaMV) 35S promoter and monitored divalent cation transport in root-tonoplast vesicles from these plants in order to select particular CAX genes directing high Cd(2+) antiporter activity in root tonoplast. Comparison of seven different CAX genes indicated that all transported Cd(2+), Ca(2+), Zn(2+), and Mn(2+) to varying degrees, but that CAX4 and CAX2 had high Cd(2+) transport and selectivity in tonoplast vesicles. CAX4 driven by the CaMV 35S and FS3 [figwort mosaic virus (FMV)] promoters increased the magnitude and initial rate of Cd(2+)/H(+) exchange in root-tonoplast vesicles. Ion selectivity of transport in root-tonoplast vesicles isolated from FS3::CAX4-expressing plant lines having a range of gene expression was Cd(2+)>Zn(2+)>>Ca(2+)>>Mn(2+) and the ratios of maximal Cd(2+) (and Zn(2+)) versus maximal Ca(2+) and Mn(2+) transport were correlated with the levels of CAX4 expression. Root Cd accumulation in high CAX4 and CAX2 expressing lines was increased in seedlings grown with 0.02 muM Cd. These observations are consistent with a model in which expression of an Arabidopsis-gene-encoded, Cd(2+)-efficient antiporter in host plant roots results in greater root vacuole Cd(2+) transport activity, increased root Cd accumulation, and a shift in overall root tonoplast ion transport selectivity towards higher Cd(2+) selectivity. Results support a model in which certain CAX antiporters are somewhat more selective for particular divalent cations.

Antiporters↗

Therapeutic use of granulocyte-colony stimulating factor could conceal residual malignant cells in patients with AML1/ETO+ acute myelogenous leukemia.

We have experienced a number of cases of AML1/ETO+ acute myelogenous leukemia that showed remission based on bone marrow (BM) morphological criteria, but that revealed clonal abnormalities in most cells by fluorescence in situ hybridization (FISH). Interestingly, most of these cases had AML with AML1/ETO rearrangement. The malignant cells were differentiated and considered mature cells after granulocyte-colony stimulating factor (G-CSF) treatment. To clarify the possible mechanisms underlying this phenomenon, we investigated the expression levels of G-CSFR in AML cells with AML1/ETO rearrangement by flow cytometry and real-time polymerase chain reaction (PCR). The number of AML1/ETO+ cells expressing G-CSFR at baseline was significantly higher than that of AML1/ETO- AML cells (2673 vs 522). In addition, the G-CSFR gene was more highly expressed in AML1/ETO+ cells than in AML1/ETO- cells by real-time PCR. This study reveals that cases showing remission after treatment with G-CSF mostly had leukemia with AML1/ETO rearrangement. This finding might be explained by the higher expression of G-CSF receptor in AML1/ETO+ cells than in AML1/ETO- cells. We recommend that remission should be confirmed by FISH, because malignant clones can be differentiated and masked in morphological examination or chromosome test, especially for AML with AML1/ETO rearrangement.

Adolescent↗

Development of a Korean adult male computational phantom for internal dosimetry calculation.

A Korean adult male computational phantom was constructed based on the current anthropometric and organ volume data of Korean average adult male, and was applied to calculate internal photon dosimetry data. The stylised models of external body, skeleton, and a total of 13 internal organs (brain, gall bladder, heart, kidneys, liver, lungs, pancreas, spleen, stomach, testes, thymus, thyroid and urinary bladder) were redesigned based on the Oak Ridge National Laboratory (ORNL) adult phantom. The height of trunk of the Korean phantom was 8.6% less than that of the ORNL adult phantom, and the volumes of all organs decreased up to 65% (pancreas) except for brain, gall bladder wall and thymus. Specific absorbed fraction (SAF) was calculated using the Korean phantom and Monte Carlo code, and compared with those from the ORNL adult phantom. The SAF of organs in the Korean phantom was overall higher than that from the ORNL adult phantom. This was caused by the smaller organ volume and the shorter inter-organ distance in the Korean phantom. The self SAF was dominantly affected by the difference in organ volume, and the SAF for different source and target organs was more affected by the inter-organ distance than by the organ volume difference. The SAFs of the Korean stylised phantom differ from those of the ORNL phantom by 10-180%. The comparison study of internal dosimetry will be extended to tomographic phantom and electron source in the future.

Adult↗

Genetic variation at the perilipin locus is associated with changes in serum free fatty acids and abdominal fat following mild weight loss.

OBJECTIVE: Perilipin (PLIN) is a class of protein-coating lipid droplets in adipocytes. We aimed to examine the association between common single-nucleotide polymorphisms (SNPs) at PLIN locus with circulating free fatty acid (FFA) and abdominal fat distribution in response to weight loss. METHODS: Non-diabetic/overweight-obese Koreans (n=177) participated in a 12-week calorie restriction (-300kcal/day) program. Seven SNPs (6209T>C, 10076C>G, 10171A>T, 11482G>A, 13042A>G, 13048C>T and 14995A>T), abdominal fat areas (visceral/subcutaneous fat areas at 1st lumbar and 4th lumbar levels), serum lipids, glucose, insulin, FFA, oxidized low-density lipoprotein (LDL) and urinary 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) were examined. RESULTS: Single-nucleotide polymorphisms 10076C>G/10171A>T showed the strongest positive linkage disequilibrium (LD) (D'=0.923, R (2)=0.839, P<0.001) and SNPs11482G>A/14995A>T showed moderate positive LD (D'=0.824, R (2)=0.578, P<0.001). Calorie restriction induced 4.6% weight loss with significant abdominal fat reduction. In response to weight loss, subjects with nCA/nCA haplotypes at SNPs 10076C>G/10171A>T showed greater reduction in FFA levels than those with CA/CA haplotype (CA/CA: C/C at SNP 10076 and A/A at SNP 10171, nCA: non-CA haplotype carrier). On the other hand, subjects with nGA/nGA haplotype at SNPs 11482G>A/14995A>T had increased FFA levels with a rapid loss in abdominal fat, whereas GA/GA haplotype carriers had reduction in FFA levels. These results still remained significant after adjusting for age, gender and BMI. Prostaglandin F(2alpha) and oxidized LDL were also more reduced in GA/GA haplotype carriers than in nGA haplotype carriers. This effect remained significant after adjusting for baseline level, age, gender and BMI. Paradoxically, nGA haplotype carriers had increased levels of urinary PGF(2alpha) after weight reduction. CONCLUSION: Fasting plasma FFA changes following a modest weight loss in overweight-obese subjects are influenced by the genetic variability at the PLIN locus. Furthermore, circulating FFA changes rather than body fat itself may determine changes in lipid peroxides such as urinary PGF(2alpha) and oxidized LDL.

Adult↗

AGS3, an alpha(1-3)glucan synthase gene family member of Aspergillus fumigatus, modulates mycelium growth in the lung of experimentally infected mice.

The cell wall of human fungal pathogen Aspergillus fumigatus protects the fungus against threats from environment and interacts with the host immune system. Alpha(1-3)glucan is the major polysaccharide of Aspergillus fumigatus cell wall, and it has been shown to contribute to the virulence of diverse fungal pathogens. In A. fumigatus, three putative alpha(1-3)glucan synthase genes AGS1, AGS2 and AGS3 have been identified. AGS1 is responsible for cell wall alpha(1-3)glucan biosynthesis, but strains with deletions of either AGS1 or AGS2 are not defective in virulence [Beauvais, A., Maubon, D., Park, S., Morelle, W., Tanguy, M., Huerre, M., Perlin, D.S., Latgé, J. P., 2005. Two alpha(1-3) glucan synthases with different functions in Aspergillus fumigatus. Appl. Environ. Microbiol. 71, 1531-1538]. In contrast, we present evidence that AGS3 is also responsible for cell wall alpha(1-3)glucan biosynthesis and can modulate the virulence of A. fumigatus. An AGS3 deletion strain was found to produce faster and more robust disease than the parental strain in an experimental mouse model of aspergillosis. The apparent hyper-virulence in the AGS3-deleted mutant was correlated with an increased melanin content of the conidial cell wall, a better resistance to reactive oxygen species and a quicker germination rate. These results suggest an indirect role for AGS3 in virulence through an adaptive mechanism.

Animals↗

Ferroelectricity induced by acentric spin-density waves in YMn2O5.

The commensurate and incommensurate magnetic structures of the magnetoelectric system YMn2O5, as determined from neutron diffraction, were found to be spin-density waves lacking a global center of symmetry. We propose a model, based on a simple magnetoelastic coupling to the lattice, which enables us to predict the polarization based entirely on the observed magnetic structure. Our data accurately reproduce the temperature dependence of the spontaneous polarization, particularly its sign reversal at the commensurate-incommensurate transition.

Journal Article↗

Indole-3-acetic acid protein conjugates: novel players in auxin homeostasis.

Indole-3-acetic acid (IAA) is found in plants in both free and conjugated forms. Within the group of conjugated IAA there is a unique class of proteins and peptides where IAA is attached directly to the polypeptide structure as a prosthetic group. The first gene, IAP1, encoding for a protein with IAA as a prosthetic group, was cloned from bean (Phaseolus vulgaris). It was shown that the expression of IAP1 as a major IAA modified protein in bean seed (PvIAP1) was correlated to a developmental period of rapid growth during seed development. Moreover, this protein underwent rapid degradation during germination. Since further molecular analysis was difficult in bean, the IAP1 gene was transformed into Arabidopsis thaliana and Medicago truncatula. Expression of the bean IAP1 gene in both plant species under the control of its native promoter targeted protein expression to the seeds. In Arabidopsis no IAA was found to be attached to PvIAP1. These results show that there is specificity to protein modification by IAA and suggests that protein conjugation may be catalyzed by species specific enzymes. Furthermore, subcellular localization showed that in Arabidopsis PvIAP1 was predominantly associated with the microsomal fraction. In addition, a related protein and several smaller peptides that are conjugated to IAA were identified in Arabidopsis. Further research on this novel class of proteins from Arabidopsis will both advance our knowledge of IAA proteins and explore aspects of auxin homeostasis that were not fully revealed by studies of free IAA and lower molecular weight conjugates.

Arabidopsis↗

High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study.

An open-label, phase II non-randomised trial was conducted with darbepoetin (DAR), an erythropoiesis-stimulating factor with prolonged half-life, at a weekly dose of 300 mug subcutaneously in 62 anaemic patients with myelodysplastic syndrome (MDS) with an endogenous erythropoietin (EPO) level <500 mU/ml. Most of the patients were classified as low or intermediate 1 according to the International Prognostic Scoring System. After 12 weeks, 44 (71%) patients had an erythroid response (34 major and 10 minor), including eight of 13 patients who were previous non-responders to conventional EPO. Two additional responses (one minor and one major) occurred, in 10 non-responders, after the addition of granulocyte colony-stimulating factor (G-CSF). Thirty-six of the 46 total responders (31/35 major and 5/11 minor) continued to respond on maintenance DAR after a median of 40 weeks (range 4-84). Median dose of DAR required to maintain response was 300 microg every 14 d. The only prognostic factors of favourable response were low endogenous EPO level and low or absent red blood cell transfusion requirement. Those results suggest that high-dose DAR alone yields high erythroid response rates in anaemia of lower risk MDS, possibly equivalent to those obtained with conventional EPO + G-CSF, although this will need to be confirmed in larger and randomised trials.

Aged↗

Inhibitory effects of Lactobacillus acidophilus lysates on the cytotoxic activity of shiga-like toxin 2 produced from Escherichia coli O157:H7.

AIMS: The purpose of this study was to characterize the degree to which four cell lysates obtained from Lactobacillus acidophilus strains affected the cytotoxic activity of Escherichia coli O157:H7 in vitro and in vivo. METHODS AND RESULTS: In a cytotoxic inhibition test that used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and toxin-binding ELISA assays, the activity of shiga-like toxin 2 (Stx-2) was inhibited profoundly by the cell lysates (10 mg ml(-1)) from two strains of L. acidophilus A4 and 30SC (>85% of survival rates compared with the control) among the five strains tested. In particular, a significant decline in the virulence level of E. coli O157:H7, under the presence of the cell lysates of L. acidophilus A4, was observed by killing assay of Caenorhabditis elegans in vivo model. CONCLUSIONS: According to our results, L. acidophilus strains might be capable of attenuating the virulence of Stx-2 produced from E. coli O157:H7. SIGNIFICANCE AND IMPACT OF THE STUDY: The cell lysates of L. acidophilus can be applied to a variety of foods, and can be used as adjuncts for the inhibition of Stx-2-mediated cytotoxicity.

Animals↗

A Phe389Leu substitution in ergA confers terbinafine resistance in Aspergillus fumigatus.

Replacement of phenylalanine with leucine at position 391 in squalene epoxidase was identified as being responsible for terbinafine resistance in mutants of Aspergillus nidulans. The equivalent mutation was engineered into the ergA gene of Aspergillus fumigatus, resulting in an F389L substitution that also conferred resistance to this pathogenic mold.

Amino Acid Sequence↗