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Biomedical subjects

J H Cho

Publications and source records attributed to J H Cho.

At least 37 records · Page 2Linked to original sources

Cascade control strategy for external carbon dosage in predenitrifying process.

We propose a cascade control strategy composed of two Proportional-Integral (PI) controllers to regulate the nitrate concentration in the predenitrifying process by manipulating the external carbon dosage. It controls the nitrate concentrations in the effluent as well as in the final anoxic reactor simultaneously to strictly satisfy the quality of the effluent as well as to remove the effects of disturbances more quickly. The design of two PI controllers in the cascade control loop can be completed with the Ziegler-Nichols (Z-N) tuning rule together with a simple relay feedback identification method. Results from the Benchmark simulation confirm that both good set point tracking and satisfactory disturbance rejection can be guaranteed due to the structural advantages of the proposed cascade control strategy. Also, compared with a previous work, the fluctuation of the nitrate concentration in the effluent has been decreased significantly.

Algorithms↗

The modulation of the biological activities of mitochondrial histone Abf2p by yeast PKA and its possible role in the regulation of mitochondrial DNA content during glucose repression.

The mitochondrial histone, Abf2p, of Saccharomyces cerevisiae is essential for the maintenance of mitochondrial DNA (mtDNA) and appears to play an important role in the recombination and copy number determination of mtDNA. Abf2p, encoded by a nuclear gene, is a member of HMG1 DNA-binding protein family and has two HMG1-Box domains, HMG1-Box A and B. To investigate the role of Abf2p in the control of mtDNA copy number, we asked if the in vivo functions of Abf2p are regulated by the possible modification such as phosphorylation. We found that the N-terminal extended segment (KRPT(21)S(22)) of HMG1-Box A is rapidly and specifically phosphorylated by cAMP-dependent protein kinase (PKA) in vitro. The phosphorylation in this region inhibits the binding of Abf2p to all kinds of DNA including four-way junction DNA and the supercoiling activity of Abf2p itself. The abf2 mutant cells with an abf2(T21A/S22A) allele defective in the phosphorylation site have a severe defect in the regulation of mtDNA content during glucose repression in vivo. These observations suggest that the phosphorylation via PKA, that is activated during glucose repression, may regulate the in vivo functions of Abf2p for the control of mtDNA content during shift from gluconeogenic to fermentative growth.

Alleles↗

Semiquantitative, bar code version of immunochromatographic assay system for human serum albumin as model analyte.

An immunochromatographic assay system was devised that can express the concentration ranges of analyte (e.g., urinary human serum albumin) as distinct numbers of the ladder bar (bar coding) for semiquantitation. We constructed a model system consisting of five membrane pad strips partially superimposed in a length. Upon wicking of sample from the bottom, the medium dissolved two different biotinylated species, antibody to the analyte and conjugates of the antibody with colloidal gold, and antigen-antibody reactions took place in the hollow space of the glass fiber membrane. After eliminating unreacted biotinylated molecules at the next strip with an immobilized albumin, the immune complexes were transferred to the pad with streptavidin immobilized in a ladder bar pattern. Analytical conditions here were set for competition between the two biotinylated species for the streptavidin binding sites. The degree of such competition was proportional to the analyte concentration and, consequently, the bar signal number was elevated as the concentration increased. Under optimal conditions for sensitivity, the analytical system responded to the analyte doses at between 30 and 120 mg/dL by producing different bar codes within 5 min.

Chromatography↗

Cross-priming as a predominant mechanism for inducing CD8(+) T cell responses in gene gun DNA immunization.

DNA immunization induces CD8(+) CTL responses by bone marrow-derived APCs, which are directly transfected with a plasmid DNA and/or acquire Ags from DNA-transfected non-APCs. To investigate the relative contribution of DNA-transfected APCs vs non-APCs to the initiation of CD8(+) T cell responses, we used tissue-specific promoter-directed gene expression and adoptive transfer systems in gene gun DNA immunization. In this study, we demonstrated that non-APC-specific gene expressions induced significant CD8(+) CTL and IFN-gamma-producing cells and Ab responses, whereas APC-specific gene expressions led to moderate CTL and IFN-gamma-producers, but no Ab responses. Interestingly, mice immunized with a non-APC-specific plasmid induced more rapid, vigorous, and prolonged proliferation of adoptively transferred Ag-specific CD8(+) T cells than APC-specific plasmid-immunized mice. In addition, the in vivo proliferative responses elicited by a non-APC-specific plasmid administration were dependent on TAP, but were independent of CD4(+) T cell help. Collectively, our results suggest that cross-priming, in which Ags expressed in non-APCs are taken up, processed, and presented by APCs, plays an important role in the initiation, magnitude, and maintenance of CD8(+) T cell responses in gene gun DNA immunization.

Adoptive Transfer↗

The role of Tyr248 probed by mutant bovine carboxypeptidase A: insight into the catalytic mechanism of carboxypeptidase A.

We have investigated the function of Tyr248 using bovine wild-type CPA and its Y248F and Y248A mutants to find that the K(M) values were increased by 4.5-11-fold and the k(cat) values were reduced by 4.5-10.7-fold by the replacement of Tyr248 with Phe for the hydrolysis of hippuryl-L-Phe (HPA) and N-[3-(2-furyl)acryloyl]-Phe-Phe (FAPP), respectively. In the case of O-(trans-p-chlorocinnamoyl)-L-beta-phenyllactate (ClCPL), an ester substrate, the K(M) value was increased by 2.5-fold, and the k(cat) was reduced by 20-fold. The replacement of Tyr248 with Ala decreased the k(cat) values by about 18- and 237-fold for HPA and ClCPL, respectively, demonstrating that the aromatic ring of Tyr248 plays a critical role in the enzymic reaction. The increases of the K(M) values were only 6- and 5-fold for HPA and ClCPL, respectively. Thus, the present study indicates clearly that Tyr248 plays an important role not only in the binding of substrate but also in the enzymic hydrolysis. The kinetic results may be rationalized by the proposition that the phenolic hydroxyl of Tyr248 forms a hydrogen bond with the zinc-bound water molecule, causing further activation of the water molecule by reducing its pK(a) value. The pH dependency study of k(cat) values and the solvent isotope effects also support the proposition. A unified catalytic mechanism is proposed that can account for the different kinetic behavior observed in the CPA-catalyzed hydrolysis of peptide and ester substrates.

Amino Acid Sequence↗

Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer.

PURPOSE: The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. METHODS AND MATERIALS: There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. RESULTS: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients). CONCLUSION: This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer.

Adenocarcinoma↗

A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease.

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, which is thought to result from the effect of environmental factors in a genetically predisposed host. A gene location in the pericentromeric region of chromosome 16, IBD1, that contributes to susceptibility to Crohn's disease has been established through multiple linkage studies, but the specific gene(s) has not been identified. NOD2, a gene that encodes a protein with homology to plant disease resistance gene products is located in the peak region of linkage on chromosome 16 (ref. 7). Here we show, by using the transmission disequilibium test and case-control analysis, that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease. Wild-type NOD2 activates nuclear factor NF-kappaB, making it responsive to bacterial lipopolysaccharides; however, this induction was deficient in mutant NOD2. These results implicate NOD2 in susceptibility to Crohn's disease, and suggest a link between an innate immune response to bacterial components and development of disease.

Adult↗

Critical adsorption in the weak surface field limit.

We study critical adsorption in the small surface field (h(1)) limit using a homologous series of critical liquid mixtures. The experiment data, in the one-phase regime, is accurately described by a universal surface scaling function G+(z/xi(+),z/l(h)) at distance z from the interface with correlation length xi(+) and surface field length l(h) approximately absolute value of (h(1))(-nu/Delta(1)), where h(1) approximately Deltasigma, the surface energy difference between the two components.

Journal Article↗

Synthesis and biological properties of C-2, C-8, N-9 substituted 6-(3-chloroanilino)purine derivatives as cyclin-dependent kinase inhibitors. Part II.

In this study, C-2, C-8, N-9 substituted 6-(3-chloroanilino)purine derivatives were synthesized and their inhibitory effects on cyclin-dependent kinases (CDK2, 4) as well as their cytotoxicities were evaluated. The effects of substituents at the C-2, C-8, and N-9 positions of the substituted purine were investigated. Among the compounds tested, [6-(3-chloroanilino)-2-(2-hydroxymethyl-4-hydroxypyrrolidyl)-9- isopropylpurine] (4h) was the most active inhibitor of CDK2 with IC50 of 0.3 microM, i.e. a two-fold increased inhibitory activity as compared to roscovitine. Results from structure-activity relationship studies should allow the design of more potent and selective CDK2 inhibitors, which may provide an effective therapy for cancer or other CDK-dependant diseases.

Antineoplastic Agents↗

Quantification of F-18 FDG PET images in temporal lobe epilepsy patients using probabilistic brain atlas.

A probabilistic atlas of the human brain (Statistical Probabilistic Anatomical Maps: SPAM) was developed by the international consortium for brain mapping (ICBM). It is a good frame for calculating volume of interest (VOI) in many fields of brain images. After calculating the counts in VOI using the product of probability of SPAM images and counts in FDG images, asymmetric indices (AI) were calculated and used for finding epileptogenic zones in mesial temporal lobe epilepsy (mTLE). FDG PET images from 18 surgically confirmed mTLE patients and 22 age-matched controls were spatially normalized to the average brain MRI template of ICBM. Counts from normalized PET images were multiplied with the probability of 12 VOIs from SPAM images in both temporal lobes. Finally AI were calculated on each pair of VOIs, and compared with visual assessment. If AI of mTLE patients were not within 2.9 standard deviation from those of normal control group (P < 0.008; Bonferroni correction for P < 0.05), epileptogenic zones were considered to be found successfully. The counts of VOIs in the normal control group were symmetric (AI < 4.3%, paired t test P > 0.05) except for those of the inferior temporal gyrus (P < 0.001). By AIs in six pairs of VOIs, PET in mTLE had deficit on one side (P < 0.05). Lateralization was correct in only 14/18 of patients by AI, but 17/18 were consistent with visual inspection. In three patients with normal AI, PET images were symmetric on visual inspection. The asymmetric indices obtained by taking the product of the statistical probability anatomical map and FDG PET, correlated well with visual assessment in mTLE patients. SPAM is useful for the quantification of VOIs in functional images.

Adult↗

Lignan and neolignan glycosides from Ulmus davidiana var. japonica.

Four lignan xylosides and two neolignan glycosides were isolated from the stem and root barks of Ulmus davidiana var. japonica. Their structures were identified as lyoniside, nudiposide, 5'-methoxyisolariciresinol-9'-O-beta-D-xylopyranoside, isolariciresinol-9'-O-1-D-xylopyranoside, rel-trans-dihydrodehydroconiferyl alcohol 4'-O-alpha-L-rhamnopyranoside and icariside E3 by comparison of their spectral data with those reported in the literatures, respectively.

Chromatography, Ion Exchange↗

Update on the genetics of inflammatory bowel disease.

Crohn's disease and ulcerative colitis are related genetic disorders. Epidemiologic studies suggest that both disorders are caused by a complex interplay of genetic and environmental factors. Genetic linkage studies identify the general chromosomal locations of disease susceptibility genes, and a number of genetic linkages have been reported in inflammatory bowel disease (IBD). Most notable among these linkage regions has been the linkage in the pericentromeric region of chromosome 16, IBD1, among families multiply affected with Crohn's disease. Recent studies have established that at least three coding region variants in the Nod2 gene are responsible for the linkage findings here, and Nod2 therefore represents the first definitively established gene contributing to the pathogenesis of IBD. The implications of these findings for advancing our understanding of Crohn's disease are discussed.

Genetic Linkage↗

Simultaneous sternothoracic cardiopulmonary resuscitation: a new method of cardiopulmonary resuscitation.

No existing device for cardiopulmonary resuscitation (CPR) is designed to exploit both the "cardiac pump" and the "thoracic pump" effect simultaneously. The purpose of this study was to measure the haemodynamic effect of a new simultaneous sternothoracic cardiopulmonary resuscitation (SST-CPR) device that could compress the sternum and constrict the thoracic cavity simultaneously in a canine cardiac arrest model. After 4 min of ventricular fibrillation, 24 mongrel dogs were randomized to receive standard CPR (n=12) or SST-CPR (n=12). SST-CPR generated a new pattern of the aortic pressure curve presumed to be the result of both sternal compression and thoracic constriction. SST-CPR resulted in significantly higher mean arterial pressure than standard CPR (68.9+/-16.1 vs. 30.5+/-10.0 mmHg, P<0.01). SST-CPR generated higher coronary perfusion pressure than standard CPR (47.0+/-11.4 vs. 17.3+/-8.9 mmHg, P<0.01). End tidal CO(2) tension was also higher during SST-CPR than standard CPR (11.6+/-6.1 vs. 2.17+/-3.3 mmHg, P<0.01). In this preliminary animal model study, simultaneous sternothoracic cardiopulmonary resuscitation generated better haemodynamic effects than standard, closed chest cardiopulmonary resuscitation.

Animals↗

Changes of aortic dimensions as evidence of cardiac pump mechanism during cardiopulmonary resuscitation in humans.

The mechanism of forward blood flow during cardiopulmonary resuscitation (CPR) remains controversial. We hypothesized that, if the heart acts as a pump, the proximal descending thoracic aorta would be distended during compression by forward blood flow, and would be constricted or remained unchanged if blood flow is generated by increased intrathoracic pressure. Fourteen patients with nontraumatic cardiac arrest underwent transesophageal echocardiography to verify changes in the descending thoracic aorta during standard manual CPR. The aortic dimensions, including cross-sectional area and diameter at the end of compression and relaxation, were measured proximal to, and at the maximal compression site of the descending thoracic aorta. At the maximal compression site, deformation of the descending thoracic aorta was observed during compression in all patients and the ratio of maximal to minimal diameter of the aorta (deformation ratio) decreased during compression compared with relaxation (0.58+/-0.15 vs. 0.81+/-0.11, P=0.001). This suggests eccentric compression of the descending thoracic aorta by external chest compression. The deformation ratio of the descending thoracic aorta proximal to the maximal compression site remained unchanged during compression and relaxation (1.0+/-0.88 vs. 1.0+/-0.9, P=0.345). The cross-sectional area of the descending thoracic aorta proximal to the maximal compression site increased 15% on average during compression compared with relaxation in 12 of 14 patients. In conclusion, deformation of the aorta at the maximal compression site and increase in the cross-sectional area of the proximal aorta suggests that cardiac pumping is the dominant mechanism in generating forward blood flow during CPR in humans.

Adult↗

Overexpression of BETA2/NeuroD induces neurite outgrowth in F11 neuroblastoma cells.

BETA2/NeuroD, a basic helix-loop-helix (bHLH) transcription factor, has been shown to play important roles in the development of the nervous system and the maintenance and formation of pancreatic and enteroendocrine cells. The gain of function of BETA2/NeuroD in neurogenesis has been shown in Xenopus embryos. In this study, we investigated the neurogenic potential of BETA2/NeuroD using neuroblastoma cell line, F11, which could be induced to differentiate into neurons in the presence of cAMP. To induce or block the expression of BETA2/NeuroD, expression vectors for the full-length and a C-terminal deletion mutant of BETA2 were constructed and their transactivation potential was verified using reporter genes containing the insulin promoter sequences. Overexpression of BETA2 with full-length construct induced neurite outgrowth in F11 cells in the absence of cAMP. In contrast, the C-terminal deletion mutant, BETA2(1--233), which has dominant negative activity, inhibited neurite outgrowth induced by cAMP in F11 cells. These results indicate that BETA2/NeuroD plays an important role in terminal differentiation of neuroblastoma cells. They also imply that BETA2/NeuroD or related bHLH factors plays an essential role for differentiation of F11 neuroblastoma cells.

Animals↗

Expression of human beta-defensin 1 mRNA in human palatine tonsil.

Defensins are a newly delineated family of effector molecules whose contribution to host defense, inflammation and cytotoxicity may be considerable for humans. Beta-defensins are cationic peptides with broad-spectrum antimicrobial activity that are produced by epithelia at the mucosal surface. Tonsillar epithelium, which is constantly exposed to microorganisms, may express these natural antibiotic peptides as part of its protective function. In this study we searched for the expression of hBD-1 mRNA in palatine tonsillar epithelium without signs of infection, using reverse transcriptase-polymerase chain reaction and in situ hybridization. Total RNA was isolated from non-infected tonsil and hBD-1 mRNA was identified in these tissues. From in situ hybridization, the expression of hBD-1 mRNA was seen to be localized in the surface epithelia of palatine tonsil. These data suggest that hBD-1 of the palatine tonsil may also play an important role in innate defense against microorganisms.

Adolescent↗

Magnetic resonance imaging of reconstructed anterior cruciate ligament.

After anterior cruciate ligament reconstruction with autologous patellar tendon, 23 patients who had clinically stable knees were studied prospectively with sequential magnetic resonance imaging 1, 2, 3, 6, and 12 months after surgery. The images of the anterior cruciate ligament were obtained with a 1.5 tesla magnetic resonance scanner in the oblique sagittal, coronal, and oblique axial planes. The cross-sectional area and signal intensity on the reconstructed anterior cruciate ligament were measured in an oblique axial image. The usefulness of the oblique axial image in evaluating the integrity of the reconstructed anterior cruciate ligament was seen. The result showed that the diameter of the graft increased by 70% of its initial size and the signal intensity of the reconstructed graft also showed a tendency to increase. In three patients, there was discontinuity in the graft direction on the oblique sagittal image, but on the oblique axial image there was no evidence of reconstructed anterior cruciate ligament rupture in the sequential images. This shows the value of the oblique axial image in evaluating the integrity of the reconstructed anterior cruciate ligament. Also, sufficient notchplasty in anterior cruciate ligament reconstruction may be needed to prevent graft impingement.

Adolescent↗