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J K Park

Publications and source records attributed to J K Park.

At least 19 recordsLinked to original sources
PubMed2002

The identification of eight novel glucocerebrosidase (GBA) mutations in patients with Gaucher disease.

Mutations in the gene encoding for the lysosomal enzyme glucocerebrosidase (GBA) result in Gaucher disease. In this study, seven novel missense mutations in the glucocerebrosidase gene (A136E, H162P, K198E, Y205C, F251L, Q350X and I402F) and a splice site mutation (IVS10+2T-->A) were identified by direct sequencing of three amplified segments of the glucocerebrosidase gene. Five of the novel mutations were found in patients with neuronopathic forms of Gaucher disease, two of which, K198E and F251L, appear to be associated with type 2 Gaucher disease.

Alleles↗
PubMed2002

The E326K mutation and Gaucher disease: mutation or polymorphism?

Gaucher disease is caused by mutations in the gene for human glucocerebrosidase, a lysosomal enzyme involved in the intracellular hydrolysis of glucosylceramide. While over 150 different glucocerebrosidase mutations have been identified in patients with Gaucher disease, not all reported mutations have been fully characterized as being causative. One such mutation is the E326K mutation, which results from a G to A nucleotide substitution at genomic position 6195 and has been identified in patients with type 1, type 2 and type 3 Gaucher disease. However, in each instance, the E326K mutation was found on the same allele with another glucocerebrosidase mutation. Utilizing polymerase chain reaction (PCR) screening and restriction digestions of both patients with Gaucher disease and normal controls, we identified the E326K allele in both groups. Of the 310 alleles screened from patients with Gaucher disease, the E326K mutation was detected in four alleles (1.3%). In addition, screening for the E326K mutation among normal controls from a random population revealed that three alleles among 316 screened (0.9%) also carried the E326K mutation. In the normal controls with the E326K allele, the glucocerebrosidase gene was completely sequenced, but no additional mutations were found. Because the E326K mutation may be a polymorphism, we caution that a careful examination of any allele with this mutation should be performed to check for the presence of other glucocerebrosidase mutations.

Alleles↗
PubMed2002

Comparison of effects of angiotensin peptides in the regulation of clitoral cavernosum smooth muscle tone.

The isometric tension measurement and in vitro autoradiography were used in clitoral cavernosum smooth muscle (CSM). Angiotensin ANG III, ANG IV, ANG II and ANG I induced contractions in clitoral CSM strips. ANG III and ANG I- induced contraction was five times less active than ANG II, whereas ANG IV-induced contraction was 1181-fold less potent than ANG II. Contractile responses to ANG III, ANG IV, ANG II and ANG I were significantly inhibited by type 1 ANG II (AT 1) receptor antagonist Dup 753 but not by type 2 ANG II (AT2) receptor antagonist PD 123,319. Pre-treatment with Nomega-nitro-L-arginine methyl ester, nitric oxide (NO) synthase inhibitor accentuated force of contraction induced by ANG III, ANG IV and ANG II. Amastatin, an aminopeptidase inhibitor enhanced ANG III- and ANG IV-induced contractions. Specific binding sites for 125I-ANG II were found in the clitoral CSM. Specific binding of 125I-ANG II was displaced by unlabeled ANG peptides. This study suggests that the contractile responses to all four peptides of the ANG family are mediated via AT1 receptors but not AT2 receptors. Further, the rank order of potency of contraction was as follows, ANG II> ANG I>ANG III>ANG IV. It is also suggested that peptides of the ANG family have a cross-talk with the NO system and aminopeptidase is involved in the modulation of the tone of clitoral CSM by ANG III and ANG IV.

Acetylcholine↗
PubMed2002

Tissue-engineered heart valve leaflets: an effective method of obtaining acellularized valve xenografts.

UNLABELLED: To determine the most effective method of producing the acellularized xenograft heart valve leaflets, we compared pathological findings of the xenograft heart valve leaflets produced by three methods; freeze-thawing, Triton and NaCl-SDS treatment and further analyzed the pattern of endothelial cells seeded onto them. MATERIALS AND METHODS: Two pigs were sacrificed and three pulmonary valve leaflets were harvested from each animal. They were immediately stored in a tissue preservation solution and assigned in one of the three preparation methods for acellularization. Endothelial cells from the jugular vein of a goat were isolated and seeded onto the acellularized xenograft heart valve leaflets. Light and Electron microscopic analyses were performed. RESULT AND CONCLUSION: H & E stain showed that cells were almost absent in the leaflet treated with NaCl-SDS, while cells were partly present in the leaflets treated, one with Triton and the other Freeze-thawing. Transmission microscopic analyses showed cell-free matrix with well preserved collagen architecture under the seeded endothelial cells in the leaflets treated with NaCl-SDS. In conclusion, the valve leaflets treated with NaCl-SDS among three representative methods of acellularization of tissues (freeze-thawing, Triton X-100, and NaCl-SDS) showed the better results than the others in terms of the efficacy of decellularization and response to endothelial cell seeding.

Animals↗
PubMed2002

Competition between polyphosphate- and glycogen-accumulating organisms in biological phosphorus removal systems--effect of temperature.

This study demonstrated that temperature is an important factor in determining the outcome of competition between polyphosphate-accumulating organisms (PAOs) and glycogen-accumulating non-poly-P organisms (GAOs) and the resultant stability of enhanced biological phosphorus removal (EBPR) systems. At 20 degrees C and a 10-day sludge age, PAOs were dominant in the anaerobic/aerobic (A/O) SBR, however, at 30 degrees C and a 10-day sludge age, GAOs were dominant in the A/O SBR. For kinetic batch studies, the anaerobic specific acetate uptake rate of GAO-dominated sludge (1.34 x 10(-3) mg C/mg VSS x minute) was higher than the rate of PAO-dominated sludge (0.89 x 10(-3) mg C/mg VSS x minute) at 30 degrees C, leading to the eventual failure of EBPR processes at high temperatures.

Bioreactors↗
PubMed2001

Protein release microparticles based on the blend of poly(D,L-lactic-co-glycolic acid) and oligo-ethylene glycol grafted poly(L-lactide).

Bovine serum albumin (BSA), a model protein drug, was encapsulated with a microparticle based on the blend of poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactide)-g-oligo(ethylene glycol) (PLLA-g-oligoEG). Effects of PLLA-g-oligoEG in the blend on degradation, characteristic properties, and release behavior of the microparticle were studied. Drug loading efficiency increased with increase in the graft frequency of oligoEG in the graft copolymer in the blend. The release of BSA was found to be more efficient for microparticles based on the blend than on the PLGA, which is due to the faster protein diffusion through the swollen phase of the hydrogel-like structure. The microparticles based on the blend showed a slower degradation and a lower pH shift compared to that of PLGA.

Calorimetry, Differential Scanning↗
PubMed2001

Ca2+-dependent membrane currents in vascular smooth muscle cells of the rabbit.

The membrane potential in vascular smooth muscle cells contributes to the regulation of cytosolic [Ca2+], which in turn regulates membrane potential by means of Ca2+i-dependent ionic currents. We investigated the characteristics of Ca2+i-dependent currents in rabbit coronary and pulmonary arterial smooth muscle cells. Ca2+i-dependent currents were recorded using the whole-cell patch-clamp technique while cytosolic [Ca2+] was increased by caffeine. The reversal potentials of caffeine-induced currents were between -80 and -10 mV under normal ionic conditions, whereas they were about 0 mV when K+-free NaCl solutions were used both in pipette and bath. The total substitution of extracellular Na+ with membrane-impermeable cation N-Methyl-D-glucamine did not affect caffeine-induced currents, implying no significant contribution of Na+ as a permeant ion to the currents. The substitution of extracellular NaCl with sucrose reduced outward component of the currents and shifted the reversal potentials according to the change in Cl- equilibrium potential. Upon application of the niflumic acid under K+-free conditions, most of the current induced by caffeine was inhibited. Taken together, the results of the present study indicate that K+ and Cl- currents are major components of Ca2+i-dependent currents in vascular smooth muscles isolated from coronary and pulmonary arteries of the rabbit, and the relative contribution of each type of current to total currents are not different between the two arteries.

Animals↗
PubMed2001

Characterization of mutations, including a novel regulatory defect in the first intron, in Bruton's tyrosine kinase gene from seven Korean X-linked agammaglobulinemia families.

In this report, we describe seven mutations, including a novel single base pair substitution in intron 1, of the Bruton's tyrosine kinase (Btk) gene found in 12 Korean patients with X-linked agammaglobulinemia. Various mutations, including three novel genetic alterations, were discovered using single-strand conformation polymorphism analysis and direct DNA sequencing. The effect of the intron 1 point mutation (intron 1 +5G-->A) was further evaluated using reporter constructs. Using luciferase assay experiments, we showed that the transcriptional activity of the mutant was significantly lower than in normal counterparts, indicating that the intronic mutation was functional. In addition, DNase I footprinting analysis showed that a single protected region spanning the position +3 to +15 bp hybridized with a mutant-specific probe, but not with a wild-type probe. EMSA indicated that a distinct nuclear protein has the ability to bind the mutant oligonucleotides to produce a new DNA-protein complex. We also observed decreased expression of Btk proteins in monocytes of patients having the point mutation in intron 1. Taken together with the functional analysis, our results strongly suggest the existence of a novel cis-acting element, which might be involved in the down-regulation of Btk gene transcription. Precise definition of the regulatory defect in the Btk intron 1 may provide valuable clues toward elucidating the pathogenesis of X-linked agammaglobulinemia.

Adolescent↗
PubMed2001

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↗
PubMed2001

Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors.

The most common primary tumors of the human brain are thought to be of glial cell origin. However, glial cell neoplasms cannot be fully classified by cellular morphology or with conventional markers for astrocytes, oligodendrocytes, or their progenitors. Recent insights into central nervous system tumorigenesis suggest that novel molecular markers might be found among factors that have roles in glial development. Oligodendrocyte lineage genes (Olig1/2) encode basic helix-loop-helix transcription factors. In the rodent central nervous system, they are expressed exclusively in oligodendrocytes and oligodendrocyte progenitors, and Olig1 can promote formation of an chondroitin sulfate proteoglycon-positive glial progenitor. Here we show that human OLIG genes are expressed strongly in oligodendroglioma, contrasting absent or low expression in astrocytoma. Our data provide evidence that neoplastic cells of oligodendroglioma resemble oligodendrocytes or their progenitor cells and may derive from cells of this lineage. They further suggest the diagnostic potential of OLIG markers to augment identification of oligodendroglial tumors.

Astrocytoma↗
PubMed2001

Amelioration of angiotensin II-induced cardiac injury by a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have effects that extend beyond cholesterol reduction. We used an angiotensin (Ang) II-dependent model to test the hypothesis that cerivastatin ameliorates cardiac injury. METHODS AND RESULTS: We treated rats transgenic for human renin and angiotensinogen (dTGR) chronically from weeks 4 to 7 with cerivastatin (0.5 mg/kg by gavage). We used immunohistochemistry, electrophoretic mobility shift assays, and reverse transcription-polymerase chain reaction techniques. Compared with control dTGR, dTGR treated with cerivastatin had reduced mortality, blood pressure, cardiac hypertrophy, macrophage infiltration, and collagen I, laminin, and fibronectin deposition. Basic fibroblast growth factor mRNA and protein expression were markedly reduced, as was interleukin-6 expression. The transcription factors NF-kappaB and AP-1 were substantially less activated, although plasma cholesterol was not decreased. CONCLUSIONS: These results suggest that statins ameliorate Ang II-induced hypertension, cardiac hypertrophy, fibrosis, and remodeling independently of cholesterol reduction. Although the clinical significance remains uncertain, the results suggest that statins interfere with Ang II-induced signaling and transcription factor activation, thereby ameliorating end-organ damage.

Angiotensin II↗
PubMed2001

Presumptive mechanisms of peptic ulceration by Helicobacter pylori VacA involving mucoprotease and CagA.

Helicobacter pylori vacuolating toxin (VacA) appears to be unusually stable, not only against extreme pH conditions or high temperatures, but also against common organic solvents or detergents. Under acidic conditions, its activity was markedly increased in the manner of temperature-independent, suggesting a spontaneous activation. A similar finding was also observed under alkaline conditions, however, it should have an appropriate temperature. From these observations, the mechanisms of VacA activation were suggested to be so redundant that either the case of acidic or basic amino acid residues could be involved in the VacA activation. Separately, we also found that the VacA production by H. pylori was pH-dependent: Its production was increased at a low pH region with a broad range (1.0-5.0), and at a high pH region with a narrow range (8.0-9.0). Astonishingly, a highly immunogenic CagA did not appear to be expressed under the acidic conditions. Its expression, however, was shown to be enhanced when the surrounding pH of this bacterium was raised. In contrast, mucoproteolytic activity in the H. pylori membrane was found to be increased at acidic conditions. Considering these observations, together with the stomach and duodenal pH of humans, two presumptive mechanisms of H. pylori VacA-associated ulceration may be deduced; namely, an acid- and an alkali-dependent type, involving mucoprotease and CagA, respectively.

Antigens, Bacterial↗
PubMed2001

An outbreak of typhoid fever, Xing-An County, People's Republic of China, 1999: estimation of the field effectiveness of Vi polysaccharide typhoid vaccine.

To evaluate the effectiveness of Vi polysaccharide vaccine (Vi vaccine) in preventing typhoid fever, an analysis was done of an outbreak of typhoid fever among students attending a middle school in the People's Republic of China, where Vi vaccine is licensed for use. Vi vaccine effectiveness was analyzed by using Cox proportional hazards modeling to account for the time-dependent nature of vaccination and illness status during the outbreak. Among 1260 students who had been immunized before the outbreak, receipt of Vi vaccine was associated with 73% (95% confidence interval [CI], 32%-89%) protection. Among the additional 441 students immunized during the outbreak, receipt of Vi vaccine was associated with 71% (95% CI, -9% to 92%) protection. These results provide the first evidence about the effectiveness of Vi vaccine when deployed routinely in a typhoid-endemic area and support the use of Vi vaccine as a public health tool to control typhoid fever.

Adolescent↗
PubMed2001

Gain- and loss-of-function of Rhp51, a Rad51 homolog in fission yeast, reveals dissimilarities in chromosome integrity.

Rad51 is crucial not only in homologous recombination and recombinational repair but also in normal cellular growth. To address the role of Rad51 in normal cell growth we investigated morphological changes of cells after overexpression of wild-type and a dominant negative form of Rad51 in fission yeast. Rhp51, a Rad51 homolog in Schizosaccharomyces pombe, has a highly conserved ATP-binding motif. Rhp51 K155A, which has a single substitution in this motif, failed to rescue hypersensitivity of a rhp51 mutant to methyl methanesulfonate (MMS) and UV, whereas it binds normally to Rhp51 and Rad22, a Rad52 homolog. Two distinct cellular phenotypes were observed when Rhp51 or Rhp51 K155A was overexpressed in normal cells. Overexpression of Rhp51 caused lethality in the absence of DNA-damaging agents, with acquisition of a cell cycle mutant phenotype and accumulation of a 1C DNA population. On the other hand, overexpression of Rhp51 K155A led to a delay in G(2) with decondensed nuclei, which resembled the phenotype of rhp51. The latter also exhibited MMS and UV sensitivity, indicating that Rhp51 K155A has a dominant negative effect. These results suggest an association between DNA replication and Rad51 function.

Adenosine Triphosphate↗
PubMed2001

Glucocerebrosidase mutations among African-American patients with type 1 Gaucher disease.

While the inherited deficiency of the enzyme glucocerebrosidase (Gaucher disease) is panethnic in its distribution, there have not been studies of the mutations encountered in specific ethnic groups in the United States, other than those on Ashkenazi Jews. We present the clinical descriptions and genotypes of seven patients of African-American ancestry with type 1 Gaucher disease, and summarize the published literature regarding the genotypes encountered in this population. All seven of the patients had moderate-to-severe manifestations of the disease, and all developed symptoms by adolescence. Genotypic analyses revealed that no two probands shared the same genotype. The common mutations N370S, c.84-85insG, IVS2+1 G-->A, and R463C were not seen. Mutation L444P was present on one allele in each of the patients; but the same mutation was encountered as a single point mutation in three of the patients, and as part of a recombinant allele in four of the patients. Southern blot analyses revealed a glucocerebrosidase fusion allele in one patient, and a duplication resulting from recombination in the region downstream from the glucocerebrosidase gene in three of the patients. Five different point mutations (A90T, R48W, N117D, R170C, and V352L), one deletion mutation (c.222-224 delTAC), and one insertion mutation (c.153-154 insTACAGC) were encountered. Our results demonstrate that there is significant genotypic heterogeneity among African-American patients with type 1 Gaucher disease, and that recombinations in the glucocerebrosidase gene locus are particularly common in this patient group. Published 2001 Wiley-Liss, Inc.

Adolescent↗
PubMed2001

p53, BCL-2, and Ki-67 expression according to tumor response after concurrent chemoradiotherapy for advanced rectal cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer is an important modality for curative resection, but tumors show wide spectrum response. The purpose of this study was to investigate any correlation among related genetic mutations, proliferative index, and tumor response after CCRT. METHODS: This study included 23 patients with rectal cancer, who were preoperatively staged as at least T3 N1 or T4 (determined by transrectal ultrasonography and MRI). Enrolled patients were given 5-FU 450 mg/m2/day and leucovorin 20 mg/m2/day intravenously for 5 days during weeks 1 and 5 of radiotherapy (45-54 Gy). Surgical resection was performed 4 weeks after completion of the scheduled treatment. Tumor response was classified as CR (complete response), PR (partial response: 50% diminution of tumor volume and downstaging), and NR (no response). Paraffin-embedded tissue obtained before chemoradiotherapy was studied by immunohistochemical staining for p53, BCL-2, and Ki-67. The extent of tumor response was correlated with proliferative activity and was measured by immunostaining Ki-67 proliferative antigen and the expression of p53 and BCL-2 oncoproteins. RESULTS: All patients were resectable. CR was obtained in 4 patients, PR in 10 patients, and NR in 9 patients. The p53 mutation was noted in 16 patients: NR in 5 patients, PR in 9 patients, and CR in 2 patients (P = .638). BCL-2 expression was noted in 11 patients: NR in 4 patients, PR in 3 patients, and CR in 4 patients (P = .799). The Ki-67 labeling index was NR: 615.4+/-47.2; PR: 663.2+/-20.4; and CR: 765.5+/-58.3 (CR + PR vs. NR, P = .029). CONCLUSIONS: Immunohistochemical expression of p53 and BCL-2 does not correlate with tumor response after CCRT, but Ki-67 labeling may be a useful parameter for radiosensitive tumors selected for CCRT.

Adenocarcinoma↗
PubMed2001

Pharyngo-enteral anastomosis for esophageal reconstruction in diffuse corrosive esophageal stricture.

BACKGROUND: Diseases involving the entire esophagus usually require extensive surgical procedures to accomplish functional reconstruction. These procedures are extremely stressful for undernourished patients. We have utilized a simpler procedure for total esophageal reconstruction. METHODS: This retrospective report reviews the experience in 8 patients who underwent esophageal reconstruction by pharyngo-colo-gastrostomy or jejunostomy without any resection of bony structures. RESULTS: There was no operative or hospital death. Complications included anastomotic stenosis, transient leak from the ileal stump, and late enterocutaneous fistula, each in 1 patient. Laryngeal function was maintained without special treatments. After swallowing training for approximately 1 week, oral feeding was resumed. All patients have gained 7 to 21 kg at 35 to 67 months after surgery. CONCLUSIONS: Our surgical procedure is shown to be safe and effective in undernourished patients with diffuse esophageal stricture.

Adult↗