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Biomedical subjects

J Y Chung

Publications and source records attributed to J Y Chung.

At least 19 recordsLinked to original sources

Upsilon production and polarization in p p macro collisions at square root of s = 1.8 TeV.

We report on measurements of the Upsilon(1S), Upsilon(2S), and Upsilon(3S) differential cross sections (d(2)sigma/dp(T)dy)(/y/<0.4), as well as on the Upsilon(1S) polarization in p p macro collisions at square root of s = 1.8 TeV using a sample of 77+/-3 pb(-1) collected by the collider detector at Fermilab. The three resonances were reconstructed through the decay Upsilon-->mu(+)mu(-). The measured angular distribution of the muons in the Upsilon(1S) rest frame is consistent with unpolarized meson production.

Journal Article↗

Diffractive dijet production at sqrt[s] = 630 and 1800 GeV at the Fermilab Tevatron.

We report a measurement of the diffractive structure function F(D)(jj) of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in pp collisions at sqrt[s] = 630 GeV at the Fermilab Tevatron. The ratio of F(D)(jj) at sqrt[s] = 630 GeV to F(D)(jj) obtained from a similar measurement at sqrt[s] = 1800 GeV is compared with expectations from QCD factorization and other theoretical predictions. We also report a measurement of the xi ( x-Pomeron) and beta ( x of parton in Pomeron) dependence of F(D)(jj) at sqrt[s] = 1800 GeV. In the region 0.035<xi<0.095, /t/<1 GeV2, and beta<0.5, F(D)(jj)(beta,xi) is found to be of the form beta(-1.0+/-0.1)xi(-0.9+/-0.1), which obeys beta-xi factorization.

Journal Article↗

Mechanisms of inhibition of the Ras-MAP kinase signaling pathway in 30.7b Ras 12 cells by tea polyphenols (-)-epigallocatechin-3-gallate and theaflavin-3,3'-digallate.

Our previous study showed that tea polyphenols inhibited MAP kinase and AP-1 activities in mouse epidermal JB6 cells and the corresponding H-ras-transformed cell line 30.7b Ras 12. The present study investigated the mechanisms of this inhibition. The cells were incubated with (-)-epigallocatechin-3-gallate (EGCG) or theaflavin-3,3'-digallate (TFdiG) (20 mM) for different times, and the cell lysate was analyzed by immunoblotting. EGCG treatment decreased the levels of phospho-Erk1/2 and -MEK1/2 time-dependently (by 60% at 60 min). TFdiG lowered their levels by 38%-50% at 15 min. TFdiG effectively decreased total Raf-1 protein levels, most likely through lysosomal degradation. EGCG did not affect protein levels or the activity of Raf-1 significantly but decreased its association with MEK1 as determined by co-immunoprecipitation. In addition, EGCG and TFdiG (10 mM) inhibited the phosphorylation of Elk-1 by isolated phospho-Erk1/2 in vitro. This inhibition of Erk1/2 activity is Elk-1 concentration-dependent and ATP concentration-independent, which suggests that EGCG and TFdiG interfere with the binding of the protein substrate to the kinase. The presently demonstrated specific mechanisms of inhibition of MAP kinases by EGCG and TFdiG may help us to understand the effects of tea consumption on cancer, inflammatory diseases, and cardiovascular diseases.

Adenosine Triphosphate↗

Rhabdoid tumour of the kidney: imaging findings.

BACKGROUND: Rhabdoid tumour of the kidney (RTK) is a rare tumour, but it is the most aggressive malignant neoplasm of the kidney in children. OBJECTIVE: To analyse the radiological findings of RTK in children. MATERIALS AND METHODS: The clinical and radiological findings in seven children (age range 6 months to 4.7 years; median 18 months) with pathologically proven RTK were retrospectively reviewed. We analysed tumour size, tumour location, tumour margin, subcapsular haematoma, tumour necrosis, haemorrhage, calcification and lymphadenopathy. RESULTS: Tumour size varied from 5 to 12 cm. Four tumours were located mainly in the central portion of the kidney, while three tumours were mainly sited peripherally. The margins of the tumour were ill-defined in four (57%) of seven cases, a lobulated tumour surface was depicted in all seven (100%), subcapsular haematoma was present in four (57%), tumour necrosis or haemorrhage in seven (100%), calcifications in three (43%) and retroperitoneal lymphadenopathy in four (57%). CONCLUSIONS: Imaging findings of RTK are subcapsular haematoma, a lobulated surface of the tumour, calcification and tumour necrosis or haemorrhage.

Child, Preschool↗

Plasma concentrations of haloperidol are related to CYP2D6 genotype at low, but not high doses of haloperidol in Korean schizophrenic patients.

AIMS: This study was carried out to evaluate the influence of CYP2D6 genotype on the steady state plasma concentrations of haloperidol and reduced haloperidol in Korean schizophrenic patients. METHODS: One hundred and twenty Korean schizophrenic patients treated with various, clinically determined, doses of haloperidol (range 3-60, median 20 mg day-1) during monotherapy were recruited. CYP2D6 genotypes were determined by analysis of the CYP2D6*10 allele using allele-specific PCR and the CYP2D6*5 allele by long-PCR. Steady state plasma concentrations of haloperidol and reduced haloperidol were analysed by h.p.l.c. RESULTS: Twenty-three (19.2%), 60 (50.0%), 1 (0.8%), 33 (27.5%) and 3 patients (2.5%) possessed the CYP2D6 genotypes *1/*1, *1/*10, *1/*5, *10/*10 and *10/*5, respectively. The allele frequencies of CYP2D6*1, *10 and *5 were 44.6%, 53.8% and 1.7%, respectively. Significant relationships between dose and plasma concentrations of haloperidol (linear; r2 = 0.60, P < 0.0001) and reduced haloperidol (quadratic equation; r(2) = 0.67) were observed. Overall, the concentrations normalized for dose (C/D) of haloperidol were significantly different between the CYP2D6*1/*1, *1/*10 and *10/*10 genotype groups (one-way ANOVA; P = 0.028). No significant differences between the genotype groups were found with respect to the C/D of reduced haloperidol (P = 0.755). However, in patients with daily doses less than 20 mg, significant differences in the C/D of haloperidol (P = 0.003), but not of reduced haloperidol, were found between the three major genotype groups. In patients with doses higher than 20 mg, no differences were found between the genotype groups for either haloperidol or reduced haloperidol. 68 patients (57%) used benztropine, an antimuscarinic agent. All four patients with a *5 allele (one together with *1 and three with *10) were found to use benztropine. The patients homozygous for the *1 allele seemed to need less benztropine than the patients with one or two mutated alleles (Fisher's exact test; P = 0.036). CONCLUSIONS: The dose-corrected steady state plasma concentrations of haloperidol, but not of reduced haloperidol, were significantly different between the CYP2D6*1/*1, *1/*10 and *10/*10 genotype groups when doses lower than 20 mg haloperidol were given. No differences were found at higher doses. These results suggest the involvement of CYP2D6 in the metabolism of haloperidol at low doses of haloperidol (< 20 mg daily), while another enzyme, probably CYP3A4, contributes at higher doses.

Adult↗

Clinical and radiographic outcome of femoral head fractures: 30 patients followed for 3-10 years.

The aim of this study was to evaluate the outcome of 30 femoral head fractures. We modified Pipkin's classification into 4 types: I (5 cases) small fracture of head distal to fovea centralis, which was too small or too fragmented to be fixed with screws; II (18 cases), larger fracture of head distal to fovea centralis; III (4 cases), large fracture of head proximal to fovea centralis, and IV (3 cases), comminuted fracture of head. Excision of the head fragment was done in all 5 cases of type I and in 9 type II fractures. Fixation of the head fragment was performed in 9 type II and in all 4 type III cases. The femoral head was replaced in all 3 type IV fractures. After a mean follow-up of 3-10 years, the clinical outcome, according to Epstein et al.'s critieria, were excellent in 7, good in 15, fair in 4 and poor in 1, except in type IV, and the radiographic outcome was excellent in 15, good in 7, fair in 4 and poor in 1. On the basis of our findings, we conclude that excision of the small fragment is a good choice of treatment in type 1. Early accurate reduction with stable internal fixation in type II or III permits bony union. Arthroplasty seems to be indicated in type IV.

Accidental Falls↗

Role of capsule in the pathogenesis of fowl cholera caused by Pasteurella multocida serogroup A.

We have constructed a defined acapsular mutant in Pasteurella multocida X-73 (serogroup A:1) by disrupting the hexA gene through the insertion of a tetracycline resistance cassette. The genotype of the hexA::tet(M) strain was confirmed by PCR and Southern hybridization, and the acapsular phenotype of this strain was confirmed by electron microscopy. The hexA::tet(M) strain was attenuated in both mice and chickens. Complementation of the mutant with an intact hexAB fragment restored lethality in mice but not in chickens. In contrast to the results described previously for P. multocida serogroup B (J. D. Boyce and B. Adler, Infect. Immun. 68:3463-3468, 2000), the hexA::tet(M) strain was sensitive to the bactericidal action of chicken serum, whereas the wild-type and complemented strains were both resistant. Following inoculation into chicken muscle, the bacterial count of the hexA::tet(M) strain decreased significantly, while the wild-type and complemented strains both grew rapidly over 4 h. The capsule is thus an essential virulence determinant in the pathogenesis of fowl cholera.

Animals↗

Genetic organization of Pasteurella multocida cap Loci and development of a multiplex capsular PCR typing system.

Current serotyping methods classify Pasteurella multocida into five capsular serogroups (serogroups A, B, D, E, and F) and 16 somatic serotypes (serotypes 1 to 16). In the present study, we have developed a multiplex PCR assay as a rapid alternative to the conventional capsular serotyping system. The serogroup-specific primers used in this assay were designed following identification, sequence determination, and analysis of the capsular biosynthetic loci of each capsular serogroup. The entire capsular biosynthetic loci of P. multocida A:1 (X-73) and B:2 (M1404) have been cloned and sequenced previously (J. Y. Chung, Y. M. Zhang, and B. Adler, FEMS Microbiol. Lett. 166:289-296, 1998; J. D. Boyce, J. Y. Chung, and B. Adler, Vet. Microbiol. 72:121-134, 2000). Nucleotide sequence analysis of the biosynthetic region (region 2) from each of the remaining three serogroups, serogroups D, E, and F, identified serogroup-specific regions and gave an indication of the capsular polysaccharide composition. The multiplex capsular PCR assay was highly specific, and its results, with the exception of those for some serogroup F strains, correlated well with conventional serotyping results. Sequence analysis of the strains that gave conflicting results confirmed the validity of the multiplex PCR and indicated that these strains were in fact capsular serogroup A. The multiplex PCR will clarify the distinction between closely related serogroups A and F and constitutes a rapid assay for the definitive classification of P. multocida capsular types.

Animals↗

Analysis of polymorphic regions of Plasmodium vivax Duffy binding protein of Korean isolates.

The present study was designed to investigate polymorphism in Duffy binding protein (DBP) gene of Plasmodium vivax isolates of Korea. Thirty samples were obtained from P. vivax patients in Yonchon-gun, Kyonggi-do in 1998. The PCR products of the samples were subjected to sequencing and hybridization analyses of the regions II and IV of P. vivax DBP gene. Two genotypes, SK-1 and SK-2, were identified on the basis of amino acid substitution and deletion. The genotype of 10 isolates was SK-1 and that of 20 isolates was SK-2. Most of the predicted amino acids in the region II of DBP gene were conserved between the Korean isolates and Belem strain except for 4-5 amino acid substitutions. In the region IV of DBP, a 6-bp insert that was shown in the Sal-1 allele type was found in SK-1, and a 27-bp insert that was shown in the Papua New Guinea allele type was found in SK-2. In conclusion, the present findings suggest that two genotypes of P. vivax coexist in the endemic area of Korea.

Amino Acid Sequence↗

Analysis of polymorphic region of GAM-1 gene in Plasmodium vivax Korean isolates.

The identification, characterization and quantification of Plasmodium sp. genetic polymorphism are becoming increasingly important in the vaccine development. We investigated polymorphism of Plasmodium vivax GAM-1 (PvGAM-1) gene in 30 Korean isolates. The polymorphic region of the PvGAM-1 gene, corresponding to nt 3792-4029, was amplified using polymerase chain reaction (PCR) followed by sequencing. All of the P. vivax Korean isolates were one type of GAM-1 gene, which were identical to that of the Belem strain. It is suggested that PvGAM-1 could not be used as a genetic marker for identifying or classifying P. vivax Korean isolates. It revealed that the polymorphic pattern was acquired basically by duplication and modification or deletion event of a 33 bp-motif fragment ended by poly guanine (G) and that there were at least three complete and one partial 33 bp-motif sequences within the polymorphic region in the longest cases such as those of South Korean and Belem isolates. In addition, we clustered P. vivax isolates with parsimonious criteria on the basis of PvGAM-1 polymorphic patterns (insertion/deletion patterns).

Animals↗

Osmoprotective effect of glycine betaine on foreign protein production in hyperosmotic recombinant chinese hamster ovary cell cultures differs among cell lines.

When three recombinant Chinese hamster ovary (rCHO) cell lines, CHO/dhfr-B22-4, CS13-1.00*, and CS13-0.02*, were cultivated in hyperosmolar media resulting from NaCl addition, their specific foreign protein productivity increased with medium osmolality. However, due to a simultaneous suppression of cell growth at elevated osmolality, no enhancement in the maximum foreign protein titer was made in batch cultures. To test the feasibility of using glycine betaine, known as a strong osmoprotective compound, for improved foreign protein production in hyperosmotic rCHO cell cultures, hyperosmotic batch cultures were carried out in the presence of 15 mM glycine betaine. Glycine betaine was found to have a strong osmoprotective effect on all three rCHO cell lines. Inclusion of 15 mM glycine betaine in hyperosmolar medium enabled rCHO cell lines to grow at 557 to 573 mOsm/kg, whereas they could not grow in the absence of glycine betaine. However, effect of glycine betaine inclusion in hyperosmolar medium on foreign protein production differed among rCHO cell lines. CHO/dhfr-B22-4 cells retained enhanced specific human thrombopoietin (hTPO) productivity in the presence of glycine betaine, and thereby the maximum hTPO titer obtained at 573 mOsm/kg was increased by 72% over that obtained in the control culture with physiological osmolality (292 mOsm/kg). On the other hand, enhanced specific antibody productivity of CS13-1.00* and CS13-0.02* at elevated osmolality was decreased significantly in the presence of glycine betaine. As a result, the maximum antibody titer at 557 mOsm/kg was similar to that obtained in the control culture with physiological osmolality. The mRNA contents per cell determined by northern blot hybridization correlated with q in all three rCHO cell lines, indicating that transcriptional regulation is responsible in part for q enhancement at hyperosmolality in the absence as well as the presence of glycine betaine. Taken together, efficacy of the simultaneous use of hyperosmotic pressure and glycine betaine as a means to improve foreign protein production was variable among different rCHO cell lines.

Animals↗

Pasteurella multocida capsule: composition, function and genetics.

Pasteurella multocida is an important animal pathogen and many strains express a polysaccharide capsule. The antigenicity of the capsule can be used to identify five serogroups A, B, D, E and F. Disease predilection is generally related to serogroup, with haemorrhagic septicaemia strains belonging to serogroups B or E and fowl cholera strains to serogroup A. The importance of the capsule in virulence has been implicated in a number of studies but these studies have been hampered by a lack of isogenic strains and an understanding of capsule biosynthesis at the molecular level. Recently, the nucleotide sequences and genetic organisation of the capsule biosynthetic loci have been determined for strains of P. multocida serogroups A and B.

Bacterial Capsules↗

Oxidative modification of nucleoside diphosphate kinase and its identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Nucleoside diphosphate kinase (NDPK, Nm23) has been implicated as a multifunctional protein. However, the regulatory mechanism of NDPK is poorly understood. We have examined the modification of NDPK in oxidative stresses. We found that oxidative stresses including diamide and H(2)O(2) treatment cause disulfide cross-linking of NDPK inside cells. This cross-linking was reversible in response to mild oxidative stress, and irreversible to strong stress. This suggests that disulfide cross-linked NDPK may be a possible mechanism in the modification of cellular regulation. To confirm this idea, oxidative modification of NDPK has been performed in vitro using purified human NDPK H(2)O(2) inactivated the nucleoside diphosphate (NDP) kinase activity of NDPK by producing intermolecular disulfide bonds. Disulfide cross-linking of NDPK also dissociated the native hexameric structure into a dimeric form. The oxidation sites were identified by the analysis of tryptic peptides of oxidized NDPK, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Intermolecular cross-linking between Cys109-Cys109, which is highly possible based on the X-ray crystal structure of NDPK-A, and oxidations of four methionine residues were identified in H(2)O(2)-treated NDPK. This cross-linkng was confirmed using mutant C109A (NDPK-A(C109A)) which had similar enzymatic activity as a wild NDPK-A. Mutant NDPK-A(C109A) was not cross-linked and was not easily denatured by the oxidant. Therefore, enzymatic activity and the quaternary structure of NDPK appear to be regulated by cross-linking with oxidant. These findings suggest one of the regulatory mechanisms of NDPK in various cellular processes.

Amino Acid Sequence↗

Genetic organisation of the capsule biosynthetic locus of Pasteurella multocida M1404 (B:2).

Capsules from a range of bacterial species have been shown to be major virulence determinants and capsule has been implicated in virulence in Pasteurella multocida. Moreover, capsular serogroup appears to be related to disease predilection. Haemorrhagic septicaemia strains belong to serogroup B and E, fowl cholera strains to serogroup A and atrophic rhinitis strains to serogroup D. The entire capsule biosynthetic locus of P. multocida A:1 has been cloned and its nucleotide sequence determined (Chung et al., 1998. FEMS Microbiol. Lett. 166, 289-296); however, nothing is known of the P. multocida B:2 capsule locus. In this work we have determined the nucleotide sequence and genetic organisation of the P. multocida M1404 (B:2) capsule locus. By analogy with the cap loci of other bacteria, the nucleotide sequence can be divided into three functional regions. Regions 1 and 3 comprise six genes involved in transport of the polysaccharide capsule to the cell surface. The deduced products of these genes show high similarity to proteins involved in capsule export in other bacteria. Region 2 comprises nine genes which are likely involved in biosynthesis of the polysaccharide capsule. The deduced products of three of these genes (bcbA, bcbB and bcbC) show significant similarity to proteins known to be involved in polysaccharide biosynthesis while the other six show no similarity to known proteins. However, their organisation indicates they are co-transcribed with bcbA, bcbB, bcbC and the Region 1 capsule export genes, suggesting strongly that they are also involved in capsule biosynthesis.

Amino Acid Sequence↗