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Biomedical subjects

T Park

Publications and source records attributed to T Park.

At least 19 recordsLinked to original sources

Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough.

BACKGROUND: Chronic cough is associated with increased sensitivity to inhaled capsaicin, and both tachykinins and their receptors play important roles in the cough reflex. However, associations between polymorphisms of the tachykinin receptor genes and cough sensitivity in patients with non-productive chronic cough have not been reported. METHODS: Direct sequencing was used to identify single nucleotide polymorphisms (SNPs) in the genes for the neurokinin-1 and neurokinin-2 receptors (NK-1R and NK-2R, respectively). Informative non-synonymous SNPs were scored using the single base extension method for 312 patients with chronic cough and for 100 age matched healthy controls. The cough response to capsaicin was recorded for 312 patients with chronic cough, and the potential genetic association between cough sensitivity to capsaicin and the NK-1R and NK-2R genotypes was evaluated. RESULTS: Two informative SNPs were identified in NK-2R (Gly231Glu and Arg375His), whereas no informative SNP was found in NK-1R. After adjusting for atopy, sex, age, and smoking, the prevalence of enhanced cough sensitivity to capsaicin was higher in the chronic cough patients with the 231Glu allele (p = 0.004; OR 1.69 (95% CI 1.18 to 2.42)) and the 231Glu_375Arg haplotype (p = 0.003; OR 1.71 (95% CI 1.20 to 2.24)). Moreover, the lowest capsaicin concentration to cause five consecutive coughs (C5) was significantly lower in patients with 231Glu (mean (SD) 44.1 (53.2) v 60.9 (55.8) microM/l, p = 0.04) and those with 231Glu_375Arg (43.2 (52.7) v 69.6 (52.0) microM/l, p = 0.03). CONCLUSIONS: The results of this study suggest that NK-2R gene polymorphisms are involved in the enhanced cough sensitivity to capsaicin of patients with chronic cough.

Adult↗

Proteomic analysis of the genotoxicant methylazoxymethanol (MAM)-induced changes in the developing cerebellum.

The genotoxicant methylazoxymethanol (MAM) is a widely used developmental neurotoxin, and its glucoside is an etiological factor for western Pacific amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS/PDC). Identification of global protein expression changes that occur in response to MAM in the developing cerebellum could provide valuable insight into the potential mechanisms involved in the neurodegeneration process. We have utilized fluorescence 2-dimensional differential gel electrophoresis (2D-DIGE), to determine the protein expression changes that occur during normal cerebellar development and in response to MAM. Three day-old postnatal C57BL/6 mice (PND3) received a single injection of MAM, and the cerebella of postnatal day 4 (PND4) and day 22 (PND22) were analyzed. Approximately, 1400 unique spots were matched and quantified in all samples. Comparison of PND4 and PND22 developing cerebellum showed that a significant fraction of the proteome (approximately 68%) changes at this stage. The immediate response of the developing cerebellum to MAM was minimal (approximately 10%). However, significant differences (27%) were noted 14 days after MAM exposure. In contrast, the transcriptome changes were more pronounced at 24 h compared to 14 days. MAM targeted several proteins networks including transport (e.g., alpha-synuclein), cytoskeletal (e.g., beta-tubulin, vimentin), and mitochondrial (e.g., Atp5b) proteins. Immunochemistry confirmed several of the changes in protein expression (alpha-synuclein). Comparison with gene expression changes revealed that the temporal changes observed in the transcriptome and proteome are not correlative. These studies demonstrate for the first time the potential networks involved during neuronal development and neurodegenerative processes that are perturbed by MAM.

Animals↗

The metabolic syndrome and schizophrenia: the latest evidence and nursing guidelines for management.

The introduction of second-generation antipsychotic drugs for the treatment of schizophrenia has provided significant benefits for clients experiencing this disorder. While they have been found effective in reducing psychotic symptoms, there is evidence that these drugs are also linked with a group of side effects commonly known as the metabolic syndrome. Mental health nurses are well positioned to prevent, detect and/or manage the development of this problematic constellation of symptoms. Guidelines for practice can be useful in prevention and management of the syndrome and enhance nursing care of clients who are taking second-generation antipsychotics.

Antipsychotic Agents↗

Rubella antibody loss rates in Korean children.

We followed students in eight elementary schools for rubella antibody from 1993 to 1996 (602 pairs) and 1996-9 (588 pairs) in Gyeonggi Province, Korea. We tested rubella IgG and administered rubella vaccine to the children with the titres < 10 IU/ml. The loss rates of rubella IgG during the follow-up periods were 14.3 and 15.8%, respectively. Among vaccinated groups, the loss rate was 18.8%, which was significantly higher than 13.8% of the mixture of natural and vaccine-induced immunity groups. The group that had the lower preceding antibody titre had a higher loss rate of 24.8% compared to 7.2% for the group whose titre was 40 IU/ml or above. In a multivariate analysis, age and gender were not related to antibody loss rate. Under this higher rubella antibody loss rate, in order to prevent congenital rubella syndrome, the immunization for women at childbearing age appears necessary until rubella can be eliminated or controlled.

Adult↗

Effects of covariance model assumptions on hypothesis tests for repeated measurements: analysis of ovarian hormone data and pituitary-pteryomaxillary distance data.

In the analysis of repeated measurements, multivariate methods which account for the correlations among the observations from the same experimental unit are widely used. Two commonly-used multivariate methods are the unstructured multivariate approach and the mixed model approach. The unstructured multivariate approach uses MANOVA types of models and does not require assumptions on the covariance structure. The mixed model approach uses multivariate linear models with random effects and requires covariance structure assumptions. In this paper, we describe the characteristics of tests based on these two methods of analysis and investigate the performance of these tests. We focus particularly on tests for group effects and parallelism of response profiles.

Adolescent↗

Inhibition of nicotinic acetylcholine receptors and calcium channels by clozapine in bovine adrenal chromaffin cells.

The effects of clozapine on the activities of nicotinic acetylcholine receptors (nAChRs) and voltage-sensitive calcium channels (VSCCs) were investigated and compared with those of chlorpromazine (CPZ) in bovine adrenal chromaffin cells. [(3)H]Norepinephrine ([(3)H]NE) secretion induced by activation of nAChRs was inhibited by clozapine and CPZ with half-maximal inhibitory concentrations (IC(50)) of 10.4 +/- 1.1 and 3.9 +/- 0.2 microM, respectively. Both cytosolic calcium increase and inward current in the absence of extracellular calcium induced by nicotinic stimulation were also inhibited by clozapine and CPZ, but the greater inhibition was achieved by CPZ. In addition, [(3)H]nicotine binding to chromaffin cells was inhibited by clozapine and CPZ with IC(50) values of approximately 19 and 2 microM, respectively. On the other hand, [(3)H]NE secretion induced by high K(+) was inhibited by clozapine and CPZ with similar IC(50) values of 15.5 +/- 3.8 and 17.1 +/- 3.9 microM, respectively. Our results suggest that clozapine, as well as CPZ, inhibits nAChRs and VSCCs, thereby causing inhibition of catecholamine secretion, and that clozapine is much less potent than CPZ in inhibiting nAChRs.

Adrenal Glands↗

Application of finite element analysis in neurosurgery.

With the rapid development of computer equipment, approximation by analytical solutions has become popular in mathematical modeling. Finite element (FE) analysis uses numerical methods to solve problems with physical phenomena, and these can be applied to various geometrically complex materials, such as brain. The FE formulation can provide such diverse domains as heat conduction, torsion of elastic material, diffusion and fluid flow, and it can view different objects of study in the neurosurgical field. In this article, the various applications of FE methods are introduced to illustrate the usefulness of the technique and the link between the external biomechanical aspect and internal phenomena in brain research.

Biomechanical Phenomena↗

Supranormal differential renal function is real but may be pathological: assessment by 99m technetium mercaptoacetyltriglycine renal scan of congenital unilateral hydronephrosis.

PURPOSE: It is unclear whether supranormal differential renal function of the hydronephrotic kidney is real or artifactual. We investigated the effect of clinical and renographic parameters on differential renal function. MATERIALS AND METHODS: The study included 34 males and 10 females from 1 to 9 months old (median age 2.6 months) with unilateral congenital hydronephrosis. A 99mtechnetium (Tc) mercaptoacetyltriglycine (MAG3) scan was performed, and regions of interest were drawn on the kidneys, and perirenal and lateral backgrounds. Differential renal function was calculated with and without background subtraction at 30-second intervals from 0.5 to 3 minutes after injection of 99mTc-MAG3. The effects of age, sex, obstruction, site and size of the hydronephrotic kidney were analyzed using the generalized estimating equations method. RESULTS: There were 11 right and 33 left hydronephrotic kidneys. An obstructive renographic pattern was present in 33 cases. The trends of differential renal function according to intervals were different between kidneys with and without background subtraction, and differential renal function increased significantly as size increased (p <0.05). Differential renal function of the hydronephrotic kidney with an obstructive renographic pattern increased with time when perirenal or no background subtraction was applied (p <0.05). The effects of age, sex or laterality on differential renal function were not significant. Supranormal function (differential renal function 55% or greater) was present regardless of background subtraction methods and measurement time. CONCLUSIONS: Differential renal function is higher in larger hydronephrotic kidney but function of the kidney with an obstructive pattern is overestimated on later phases of 99mTc-MAG3 renal scan. Supranormal differential renal function is real and may be pathologic since it is prone to occur in larger obstructive hydronephrotic kidneys.

Diuretics↗

An observation on the mercury contents of scalp hair in the urban residents of South Korea.

The average value of total mercury (THg) in scalp hair of male residents in Seoul city was 1.7+/-0.18 ppm (mean+/-S.E.) and that of methylmercury (MeHg), 1.0+/-0.12 ppm (58.8% THg). In female, level of THg was 1.1+/-0.15 ppm and MeHg was 0.5+/-0.14 ppm (45.5%). Mercury was found more in the scalp hair of male than female (P<0.01). THg/MeHg increased with age of subjects in male (P<0.01), but not female. Coefficients of correlation (r) between THg and MeHg contents in scalp hair of male was +0.877 (P<0.01) and that of female was +0.508 (P<0.01), respectively.

Journal Article↗

Simple pattern-mixture models for longitudinal data with missing observations: analysis of urinary incontinence data.

In longitudinal studies each subject is observed at several different times. Longitudinal studies are rarely balanced and complete due to occurrence of missing data. Little proposed pattern-mixture models for the analysis of incomplete multivariate normal data. Later, Little proposed an approach to modelling the drop-out mechanism based on the pattern-mixture models. We advocate the pattern-mixture models for analysing the longitudinal data with binary or Poisson responses in which the generalized estimating equations formulation of Liang and Zeger is sensible. The proposed method is illustrated with a real data set.

Aged↗

Nucleotide sequence of the gene for alkaline phosphatase of Thermus caldophilus GK24 and characteristics of the deduced primary structure of the enzyme.

The gene encoding Thermus caldophilus GK24 (Tca) alkaline phosphatase was cloned into Escherichia coli. The primary structure of Tca alkaline phosphatase was deduced from its nucleotide sequence. The Tca alkaline phosphatase precursor, including the signal peptide sequence, was comprised of 501 amino acid residues. Its molecular mass was determined to be 54¿ omitted¿760 Da. On the alignment of the amino acid sequence, Tca alkaline phosphatase showed sequence homology with the microbial alkaline phosphatases, 20% identity with E. coli alkaline phosphatase and 22% Bacillus subtilis (Bsu) alkaline phosphatases. High sequence identity was observed in the regions containing the Ser-102 residue of the active site, the zinc and magnesium binding sites of E. coli alkaline phosphatase. Comparison of Tca alkaline phosphatase and E. coli alkaline phosphatase structures suggests that the reduced activity of the Tca alkaline phosphatase, in the presence of zinc, is directly involved in some of the different metal binding sites. Heat-stable Tca alkaline phosphatase activity was detected in E. coli YK537, harboring pJRAP.

Alkaline Phosphatase↗

The homeodomain transcription factor NK-4 acts as either a transcriptional activator or repressor and interacts with the p300 coactivator and the Groucho corepressor.

NK-4 (tinman) encodes an NK-2 class homeodomain transcription factor that is required for development of the Drosophila dorsal mesoderm, including heart. Genetic evidence suggests its important role in mesoderm subdivision, yet the properties of NK-4 as a transcriptional regulator and the mechanism of gene transcription by NK-4 are not completely understood. Here, we describe its properties as a transcription factor and its interaction with the p300 coactivator and the Groucho corepressor. We demonstrate that NK-4 can activate or repress target genes in cultured cells, depending on functional domains that are conserved between Drosophila melanogaster and Drosophila virilis NK-4 genes. Using GAL4-NK-4 fusion constructs, we have mapped a transcriptional activation domain (amino acids 1-110) and repression domains (amino acids 111-188 and the homeodomain) and found an inhibitory function for the homeodomain in transactivation by NK-4. Furthermore, we demonstrate that NK-4-dependent transactivation is augmented by the p300 coactivator and show that NK-4 physically interacts with p300 via the activation domain. In addition, cotransfection experiments indicate that the repressor activity of NK-4 is strongly enhanced by the Groucho corepressor. Using immunoprecipitation and in vitro pull-down assays, we show that NK-4 directly interacts with the Groucho corepressor, for which the homeodomain is required. Together, our results indicate that NK-4 can act as either a transcriptional activator or repressor and provide the first evidence of NK-4 interactions with the p300 coactivator and the Groucho corepressor.

Amino Acid Sequence↗

Identification of a novel cis-acting positive element responsible for the cell-specific expression of the NK-1 homeobox gene.

The Drosophila NK-1 homeobox gene belongs to the NK-1 class that includes a large number of vertebrate homeobox genes and is shown to be expressed in specific muscle founder cells and a subset of neuronal cells in the ventral nerve cord during embryogenesis. To determine the cis-acting regulatory elements controlling the cell-specific expression of NK-1, we measured transiently expressed chloramphencol acetyl transferase (CAT) reporter gene activities from transfected C2C12 myoblasts and NG108-15 neuroblastoma cells using various CAT constructs containing different 5' upstream regions of NK-1. From the initial analysis of 3.9 kb of the 5' upstream region, we have found that the regions from -1865 to -476 and from -476 to +100 contained strong negative and positive regulatory elements, respectively. Within the positive cis-acting region an 86-bp DNA fragment (from -435 to -350) was sufficient to activate the reporter gene in C2C12 cells, whereas additional regions (from -157 to -28 and from -510 to -425) were required for optimal activity in NG108-15 cells. Gel shift and DNaseI footprinting assays have defined a plausible binding site for C/EBP, 5'-TTTCGCAAG-3' (-424 to -416), and a novel binding site for unknown factors, 5'-AATTACTCACATCC-3' (-370 to -357). Further mutation analysis has revealed that the novel binding sequence for unknown factors is necessary and sufficient for transcriptional activity for reporter gene expression in C2C12 myoblast cells in an orientation-independent manner.

Animals↗

High dietary protein and taurine increase cysteine desulfhydration in kittens.

The objective of this study was to determine the effect of dietary protein and taurine on cysteine desulfhydration in various kitten tissues. Cysteine desulfhydration was assessed in liver, kidney, skeletal muscle, heart, spleen, brain and jejunum of kittens fed one of the following diets for 5 wk: 20% protein, 0% taurine diet (LP0T); 20% protein, 0.15% taurine diet (LPNT); 60% protein, 0% taurine diet (HP0T); and 60% protein, 0.15% taurine diet (HPNT). Cats fed LP0T and HP0T had been fed a taurine-free diet for 10 wk before the 5-wk experiment. The activity of cysteine desulfhydration was determined by measuring the production of H(2)(35)S from (35)S-cysteine in the presence and absence of alpha-ketoglutarate (alphaKG) in the incubation medium. Liver and kidney had the highest total activities among the tissues tested (P < 0.01). Total hepatic desulfhydration activities [micromol H(2)S/(min. kg body wt)] in cats fed LP0T, LPNT, HP0T and HPNT were (mean +/- SEM) 117 +/- 6, 135 +/- 10, 137 +/- 10 and 190 +/- 9, respectively. Dietary taurine had a significant effect on activity when expressed per gram liver (P < 0.01), per gram protein (P < 0.05) and per kilogram body weight (P < 0.001). Dietary protein had a significant effect (P < 0.001) only when activity was expressed relative to body weight because of the significant effect of protein on relative liver weight. The direct pathway via cysteine desulfhydrase appears to be the major route of cysteine desulfhydration in kitten liver because the values obtained in the absence of alphaKG were 81-88% of those obtained in the presence of alphaKG.

Animals↗

Dietary taurine supplementation reduces plasma and liver cholesterol and triglyceride levels in rats fed a high-cholesterol or a cholesterol-free diet.

The effects of dietary taurine supplementation on plasma and hepatic lipid levels and phospholipid profiles were evaluated in rats fed a high-cholesterol or a cholesterol-free diet. Four groups of male rats were fed one of the following diets for 5 weeks: cholesterol-free diet (CFD); high cholesterol diet (HCD); high cholesterol, high taurine diet (HCHTD); or high taurine diet (HTD). Rats fed a HCHTD had significantly lower plasma levels of total cholesterol (32% reduction), LDL-cholesterol (37% reduction) and triglyceride (43% reduction) than rats fed a HCD alone. Plasma concentrations of total cholesterol, LDL-cholesterol and triglyceride were also significantly reduced in rats fed a HTD compared to rats fed a CFD. Taurine supplementation to the HCD significantly reduced hepatic cholesterol (50% decrease) and triglyceride (30% decrease) levels in rats. Taurine supplementation to the CFD also significantly reduced the hepatic triglyceride concentration (43% decrease) and elevated hepatic free fatty acid levels (77% increase) compared to rats fed only a CFD. These results suggest that dietary taurine supplementation is both hypocholesterolemic and hypotriglyceridemic in rats whose body cholesterol status is high or normal.

Animals↗

Structure-activity relationship of fluoroquinolone in Escherichia coli.

Structure-activity relationship of 20 fluoroquinolones was studied using the susceptible and 4 resistant Escherichia coli which were developed against 4 fluoroquinolones [ciprofloxacin (1), KR-10755 (6), norfloxacin (2), and ofloxacin (3)] in our laboratory. The C-7 and C-8 substituents of fluoroquinolone were important in various functions such as the inhibitory activity on DNA gyrase, permeability, and efflux. Among 20 fluoroquinolones, compounds with a 3-methyl-3,7-diazabicyclo[3.3.0]octan-1(5)-ene-7-yl substituent at the C-7 position or a chlorine substituent at the C-8 position showed a good inhibitory activity on DNA gyrase (especially a mutated DNA gyrase). Compounds with a 3,7-diazabicyclo [3.3.0]octan-1(5)-ene-7-yl substituent at the C-7 position showed good permeability in the susceptible and resistant strains, while compounds with a fluorine substituent at the C-8 position were less effluxed from cells.

Anti-Infective Agents↗

Two-year experience with ureteral stones: extracorporeal shockwave lithotripsy v ureteroscopic manipulation.

Extracorporeal shockwave lithotripsy (SWL) and ureteroscopic manipulation became the standard treatments for ureteral stones in recent years. There still exists significant debate as to the most appropriate treatment modality for ureteral stones. During a period of 2 years, from January 1994 to December 1995, 651 patients with ureteral stones were treated, and 589 patients were retrospectively reviewed, excluding 62 patients with incomplete follow-up. Four hundred forty-two patients were treated with SWL using the MPL 9000 with ultrasonic guidance and 115 patients with ureteroscopic manipulations using 7.9F to 11.5F rigid and semirigid ureteroscopes. In SWL treatments, the overall stone-free rate was 74.7% with one session. The stone-free rate was significantly affected by the size of stones, being 83.6% when the stone was <1.0 cm and 42.1% when the stone was >1.0 cm. The stone-free rate after a second SWL session was 84.4% and was 90.3% after a third session. The stone-free rates according to the site of the stone were 72.4 (proximal), 70.0 (mid), and 80.2% (distal) after a single session. In ureteroscopic manipulation, an overall stone-free rate of 87.8% was obtained regardless of the size of the stones. The success rates according to the location of stones were 75.0 (proximal), 94.6 (mid), and 86.4% (distal). Open ureterolithotomy was performed in 32 patients, with a 100% success rate. In our study, the size of the stones was the most important factor influencing the success rate of SWL treatment. We consider ureteroscopic manipulation as the first-line treatment modality when the stone is >1.0 cm, especially if it is in the distal ureter. Proper selection of patients for in situ SWL or ureteroscopy would improve the results of initial treatment.

Adult↗

Treatment of metastatic bone pain with tin-117m Stannic diethylenetriaminepentaacetic acid: a phase I/II clinical study.

The physical characteristics of Sn-117m combined with the biodistribution of the compound tin-117m (Stannic, 4+) diethylenetriaminepentaacetic acid (Sn-117m DTPA) suggest that it should be an excellent agent for the palliation of pain from bony metastases. Prior work has established the dosimetry and the safety for the material in human beings. The presence of low-energy conversion electrons should result in the relative sparing of the bone marrow while delivering a high radiation dose to sites of bony metastatic disease. Forty-seven patients with painful bone metastases from various malignancies were treated with Sn-117m DTPA. The patients were assigned to five different dose levels ranging from 2.64 to 10.58 MBq (71-286 microCi) per kg of body weight. Follow-up included review of pain diaries, performance scores, analgesic requirements, blood chemistries, and hematological assessment. Three patients received a second treatment. There was an overall response rate for relief of pain of 75% (range, 60-83%) in the 40 treatments that could be evaluated. No correlation was apparent in this limited series between response rate and the five dose levels used. The relief was complete in 12 patients (30%). The time to onset of pain relief was 19 +/- 15 days with doses < or = 5.29 MBq/kg and 5 +/- 3 days with doses > or = 6.61 MBq/kg. Myelotoxicity was minimal, with only one patient having a marginal grade 3 WBC toxicity. On the basis of our data, Sn-117m DTPA should be an effective and safe radiopharmaceutical for palliation of painful bony metastases. A large-scale trial is warranted to evaluate it in comparison to other similar agents.

Bone Marrow↗