Biomedical subjects

E M Choi

Publications and source records attributed to E M Choi.

15 recordsLinked to original sources

PubMed2003

Pair-breaking and superconducting state recovery dynamics in MgB2.

We present studies of the photoexcited quasiparticle dynamics in MgB2 where, using femtosecond optical techniques, Cooper pair-breaking dynamics (PBD) have been temporally resolved for the first time. The PBD are strongly temperature and photoexcitation intensity dependent. Analysis of the PBD using the Rothwarf-Taylor equations suggests that the anomalous PBD arises from the fact that in MgB2 photoexcitation is initially followed by energy relaxation to high frequency phonons instead of, as commonly assumed, e-e thermalization. Furthermore, the bare quasiparticle recombination rate and the probability for pair breaking by phonons have been determined.

Journal Article↗

PubMed2002

The use of chimeric A2K(b) tetramers to monitor HLA A2 immune responses in HLA A2 transgenic mice.

HLA A2 (A2) transgenic mice are currently being used to compare different vaccination protocols. However, the monitoring of A2 restricted CTL in A2 transgenic mice have been hampered by poor staining efficiency of mouse CTL by A2 tetramers. We demonstrate here that chimeric A2 tetramers containing mouse H-2K(b) (K(b)) alpha3 domain (A2K(b) tetramers) can be used as staining reagents to monitor A2 restricted CTL responses in A2 transgenic mice. The increased ability of A2K(b) tetramers to stain mouse A2 restricted CTL, as compared with A2 tetramers, correlated with their higher binding affinity for mouse A2 restricted CTL. The use of these novel staining reagents will allow efficient comparison of vaccination strategies and rapid identification of novel CTL epitopes in A2 transgenic mice.

Amino Acid Sequence↗

PubMed2001

Optical properties of c-axis oriented superconducting MgB2 films.

Temperature dependent optical conductivities and dc resistivity of c-axis oriented superconducting (T(c) = 39.6 K) MgB2 films (approximately 450 nm) have been measured. The normal state ab-plane optical conductivities can be described by the Drude model with a temperature independent Drude plasma frequency of omega(p,D) = 13 600+/-100 cm(-1) or 1.68+/-0.01 eV. The normal state resistivity is fitted by the Bloch-Grüneisen formula with an electron-phonon coupling constant lambda(tr) = 0.13+/-0.02. The optical conductivity spectra below T(c) of these films suggest that MgB2 is a multigap superconductor.

Journal Article↗

PubMed2001

High current-carrying capability in c-axis-oriented superconducting MgB2 thin films.

In high-quality c-axis-oriented MgB2 thin films, we observed high critical current densities ( J(c)) of approximately 16 MA/cm(2) at 15 K under self-fields comparable to those of cuprate high-temperature superconductors. The extrapolated value of J(c) at 5 K was estimated to be approximately 40 MA/cm(2). For a magnetic field of 5 T, a J(c) of approximately 0.1 MA/cm(2) was detected at 15 K, suggesting that this compound would be a very promising candidate for practical applications at high temperature and lower power consumption. The vortex-glass phase is considered to be a possible explanation for the observed high current-carrying capability.

Journal Article↗

PubMed2001

MgB2 superconducting thin films with a transition temperature of 39 kelvin.

We fabricated high-quality c axis-oriented epitaxial MgB2 thin films using a pulsed laser deposition technique. The thin films grown on (1 i 0 2) Al2O3 substrates have a transition temperature of 39 kelvin. The critical current density in zero field is approximately 6 x 10(6) amperes per cubic centimeter at 5 kelvin and approximately 3 x 10(5) amperes per cubic centimeter at 35 kelvin, which suggests that this compound has potential for electronic device applications, such as microwave devices and superconducting quantum interference devices. For the films deposited on Al2O3, x-ray diffraction patterns indicate a highly c axis-oriented crystal structure perpendicular to the substrate surface.

Journal Article↗

PubMed2001

Soybean ethanol extract increases the function of osteoblastic MC3T3-E1 cells.

To investigate the bioactivities of soybean, which act on bone metabolism, we studied the effect of a soybean ethanol extract on the activity of osteoblast MC3T3-E1 cells. Soy extract (0.01-0.1 g/l) dose-dependently increased survival (P<0.05) and DNA synthesis (P<0.05) of MC3T3-E1 cells. In addition, soy extract (0.05 g/l) increased alkaline phosphatase activity (P<0.05) and collagen synthesis (P<0.05) of MC3T3-E1 cells. Moreover, the anti-estrogen tamoxifen eliminated the stimulation of MC3T3-E1 cells on the proliferation, ALP activity and collagen synthesis by soy extract, indicating that the main action of the soy extract on osteoblastic MC3T3-E1 cells is similar to that of estrogen effects. Treatment with soy extract prevented apoptosis, as assessed by a one-step sandwich immunoassay and DNA gel electrophoresis studies. This effect may be associated with the activation of the estrogen receptor, since we observed soy extract-mediated survival against apoptosis was blocked by the estrogen receptor antagonist tamoxifen in cells, further supporting a receptor-mediated mechanism of cell survival. These results suggest that osteoblast function is promoted by soy extract and that the estrogen receptor is involved in the response, thereby playing an important role in bone remodeling. In conclusion, soy extract has a direct stimulatory effect on bone formation in cultured osteoblastic cell in vitro. Presumably, dietary soy products are useful in the prevention of osteoporosis.

3T3 Cells↗

PubMed2000

Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade.

We have previously shown that antibodies to CTLA-4, an inhibitory receptor on T cells, can be effective at inducing regression of transplantable murine tumors. In this study, we demonstrate that an effective immune response against primary prostate tumors in transgenic (TRAMP) mice can be elicited using a strategy that combines CTLA-4 blockade and an irradiated tumor cell vaccine. Treatment of TRAMP mice at 14 weeks of age resulted in a significant reduction in tumor incidence (15% versus control, 75%), as assessed 2 months after treatment. Histopathological analysis revealed that treated mice had a lower tumor grade with significant accumulation of inflammatory cells in interductal spaces when treated with anti-CTLA-4 and a granulocyte-macrophage colony-stimulating factor-expressing vaccine. Vaccination of nontransgenic mice with this regimen resulted in marked prostatitis accompanied by destruction of epithelium, indicating that the immune response was, at least in part, directed against normal prostate antigens. These findings demonstrate that this combinatorial treatment can elicit a potent antiprostate response and suggest potential of this approach for treatment of prostate cancer.

Abatacept↗

PubMed1999

Immunohistochemical detection of oxidative DNA damage induced by ischemia-reperfusion insults in gerbil hippocampus in vivo.

There is much evidence to suggest that ischemic injury occurs during the reperfusion phase of ischemia-reperfusion insults, and that the injury may be due to reactive-oxygen-species (ROS)-mediated oxidative events, including lipid peroxidation and DNA damage. However, oxidative DNA damage has until now not been examined in situ. In the present study, we report for the first time observation of cell type- and region-specific oxidative DNA damages in 5 min transient ischemic model by immunohistochemical methods, using monoclonal antibody against 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative DNA product. The cell types containing 8-OHdG immunoreactivity were neurons, glia and endothelial cells in the hippocampus. The 8-OHdG immunoreactivity was present in the nucleus but not the cytoplasm of these cells. The level of 8-OHdG in CA1 increased significantly (P<0.05) at the end of 30 min after ischemia, but there was no increase within CA2 and CA3 areas. The 8-OHdG levels in the hippocampus increased significantly (about fourfold) after 3 h of reperfusion and remained significantly (P<0.01) elevated for at least 12 h. At 4 days after ischemia, 8-OHdG levels in the CA2 and CA3 areas decreased to levels of the sham without neuronal loss, while disappearance of 8-OHdG immunoreactivity in the CA1 coincided with neuronal death in this area. These findings strongly suggest that ischemia-induced DNA damage evolves temporally and spatially, and that oxidative DNA damage may be involved in delayed neuronal death in the CA1 region.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1999

Thermolabile 8-hydroxyguanine DNA glycosylase with low activity in senescence-accelerated mice due to a single-base mutation.

8-hydroxyguanine (8-oxoguanine; oh8Gua) DNA glycosylase (OGG1) repairs oh8Gua, a highly mutagenic oxidative DNA damage. In the present study, we compared two strains of senescence-accelerated mouse (SAM) expressing senescence-prone phenotypes, SAMP1 and SAMP8, with one strain of SAM expressing senescence-resistant phenotype, SAMR1. We found three distinct characteristics of OGG1 in SAMPs: (i) low activity (10-40% of the SAMRI enzyme in all organs and ages observed), (ii) thermolability, and (iii) mutation from Arg (CGG) in SAMR1 to Trp (TGG) at codon 304. There was no difference in the levels of mRNA and protein. As expected, oh8Gua level in tissues was higher in the SAMPs. In contrast, O6-methylguanine-DNA methyltransferase, which repairs alkylated DNA, showed no difference in its activity. The impairment of oh8Gua repair activity caused by the 304 mutation in OGG1 may be one of the factors contributing to the high somatic mutation rate and the accelerated senescence observed in these strains.

Aging↗

PubMed1996

Induction of oh8Gua glycosylase in rat kidneys by potassium bromate (KBrO3), a renal oxidative carcinogen.

It has been suggested that 8-hydroxyguanine (oh8Gua), a DNA adduct formed by active oxygens, impairs the maintenance of genetic integrity, oh8Gua glycosylase removes oh8Gua residues as a free base from DNA strands. In E. coli, it has been demonstrated that oh8Gua glycosylase is induced in response to oxidative stress, but the oxidative inducibility in mammalian tissues has not yet been studied. In the present study, the inducibility of oh8Gua glycosylase was tested by comparing activity changes of this enzyme in the kidney and the liver of rats treated with potassium bromate (KBrO3). KBrO3 is known to cause oxidative damage to the kidney but not to other organs. With a single dose of KBrO3 (80 mg/kg, i.p.), activity in the kidney was found to increase significantly at 3 h compared to that at zero time. At 6 h, activity peaked, showing a 6-fold increase over that at zero time. Thereafter, it decreased and returned to its zero time level at 12 h. With increasing doses of KBrO3 (up to 160 mg/kg, i.p.), activity increased linearly with increased dosage, and over 40 mg/kg, i.p., activity increased to a level significantly higher than that in the control. In contrast to the time- and dose-dependent changes in activity in the kidney, no significant change was observed in the liver under the same conditions as above. These results show that oh8Gua glycosylase is also induced oxidatively in mammalian tissues. The induction in this tissue as well as in E. coli indicates that the adaptive response of this enzyme to oxidative stress is a general phenomenon in aerobic organisms and implies that the repair of oh8Gua residues in DNA is a process important for the survival of organisms in an aerobic environment.

Animals↗

PubMed1992

Point mutation at codon 12 of the c-Ha-ras gene in human gastric cancers.

The molecular mechanisms of the carcinogenic process of gastric cancer have not been fully understood yet. In order to know whether c-Ha-ras gene is being involved in the process of gastric carcinogenesis, 8 gastric cancer cell lines, 8 cases of gastric cancer and same number of adjacent dysplasia were analyzed for the presence of mutation at codon 12, 13 and 61 of the c-Ha-ras gene by using polymerase chain reaction (PCR) and mutant-specific oligonucleotide hybridization. Point mutations at codon 12 of the c-Ha-ras gene were found in 2 out of 8 gastric cancer and dysplasia samples in one case, but we found no mutation at codon 13 or 61 of the c-Ha-ras gene. These results suggest that the frequency of mutation of the c-Ha-ras gene detected by sensitive PCR technique is low indeed, however it would be notable that such a genetic change has been detected in the dysplastic lesion of the gastric cancer patient.

Base Sequence↗

PubMed1990

The CD4 molecule transmits biochemical information important in the regulation of T lymphocyte activity.

The role of the CD4 molecule in the transmission and regulation of the biochemical signals involved in T cell activation was investigated using an anti-CD4 monoclonal antibody termed 6B10. 6B10 immunoprecipitated the 55-kDa CD4 molecule and detected an epitope of CD4 that overlapped with that detected by OKT4A, B, and D. 6B10, 6B10 Fab fragments and recombinant HIV envelope glycoprotein (gp120) induced calcium mobilization in PBMC. 6B10 stimulation also resulted in calcium mobilization in murine L cells expressing transfected CD4 gene products, indicating that CD4-mediated calcium mobilization occurred independently of the CD3/T cell receptor (TCR) complex. 6B10 induced a phosphatidylinositol response, but the response resulted in reduced inositol phosphate production compared to levels obtained using OKT3. Though 6B10 caused calcium mobilization and a phosphatidylinositol response, 6B10 did not induce DNA synthesis. The amount of inositol phosphates produced by 6B10 may be below the threshold necessary for cell cycle progression. We hypothesized that 6B10-mediated calcium mobilization is important in the regulation of T cell proliferation. 6B10, but not 6B10 Fab fragments, inhibited OKT3-induced DNA synthesis. Furthermore, 6B10 but not 6B10 Fab fragments inhibited OKT3-induced calcium mobilization, suggesting that crosslinking of CD4 may be an important factor determining whether signals result in both the up- and down-regulation of CD3/TCR complex function. The implication of this work is that signals generated via the CD4 molecule are important in the regulation of T cell function and that the signals generated as a result of HIV gp120 binding to CD4 can contribute to the mechanism by which HIV inhibits T cell function.

Animals↗

PubMed1990

Mutants of staphylococcal toxic shock syndrome toxin 1: mitogenicity and recognition by a neutralizing monoclonal antibody.

Toxic shock syndrome toxin 1 (TSST-1), a 22-kilodalton protein made by strains of Staphylococcus aureus harboring the chromosomal toxin gene, may elicit toxic shock syndrome in humans. In vitro, TSST-1 induces T cells to proliferate and macrophages to secrete interleukin-1. To conduct a structure-function analysis, point mutations on the TSST-1 gene were generated by site-directed mutagenesis to identify amino acids critical for activity of the toxin. Specific tyrosine and histidine residues were replaced by alanines. Wild-type and mutant TSST-1 gene constructs were expressed in Escherichia coli, and the products were tested for their mitogenic potential and reactivity with a TSST-1 neutralizing monoclonal antibody (MAb 8-5-7). Four of the mutants were similar to the wild type; i.e., the mutant toxins stimulated murine T cells and reacted with MAb 8-5-7 equally as well as the wild type. Two mutants exhibited a decrease in mitogenic activity, but one of these retained the capacity to bind with MAb 8-5-7 while the other was no longer recognized by the same antibody. One double mutant demonstrated minimal mitogenic activity and did not react in enzyme-linked immunosorbent and immunoblot assays with MAb 8-5-7. The data show that specific residues near the carboxy terminus of TSST-1 are essential for mitogenic activity and in forming the epitope recognized by neutralizing MAb 8-5-7.

Animals↗

PubMed1989

Molecular genetics of C4B deficiency in IgA nephropathy.

The fourth component of complement (C4) occurs in two functionally distinct isotypes, C4A and C4B. The two closely linked genes are located on chromosome 6p, between HLA-B and -DR. Several reports have established complete C4B deficiency as the major genetic risk factor for IgA nephropathy (RR = 6.5; p = 0.0004). It is not clear whether this association derives from immune dysfunction related to the absent isotype or from another disease susceptibility gene closely linked to C4B. To help distinguish between these mechanisms, we examined the molecular basis of complete C4B deficiency in five patients with IgA nephropathy and eight healthy individuals. C4 and Bf protein typing were performed by immunofixation electrophoresis of plasma. Genomic DNA was digested with several restriction enzymes, chosen to produce informative restriction fragment length polymorphisms (RFLPs). After electrophoresis and Southern blotting, digests were hybridized to a series of cDNA probes specific to the 5' and 3' ends of the C4 genes, the C4d region, and the adjacent 21-hydroxylase genes. Availability of DNA from family members allowed assignment of RFLPs to specific haplotypes. The 10 C4B-deficient IgA nephropathy-associated haplotypes displayed seven different protein phenotype/RFLP patterns. Three haplotypes consisted of the common C4B/21-hydroxylase deletion on the Bf*S, C4A*3, C4B*Q0 complotype. Two haplotypes were characterized by the C4A*3,2 duplication, with two C4 genes present but a C4A protein being produced by the gene at the usual C4B locus. All of the remaining haplotypes had unique Bf, C4, and 21-hydroxylase patterns. C4B-deficient IgA nephropathy patients display a variety of molecular genetic bases for their protein deficiency. This observation speaks against linkage of C4B deficiency with a locus encoding disease susceptibility and supports a primary role for the complement abnormality in this disease.

Child↗

PubMed1987

A single base mutation in an I-A alpha-chain gene alters T-cell recognition.

The interaction between the clonally selected T-cell antigen receptor, antigen, and Ia molecule is poorly understood at the molecular level. A cell line bearing an altered I-Ak alpha-chain (Ak alpha) molecule has been examined in order to provide more information about the relationship between Ia structure and function. The cell line, 3J9, was derived from the TA3 B-cell hybridoma through a series of negative and positive immunoselection steps. The 3J9 mutant lacked the binding site recognized by the Ak alpha-specific monoclonal antibody 39J and failed to present antigen to two T-cell hybridomas out of a large panel of I-Ak-restricted T-cell hybridomas examined. Sequence analysis of the mutant Ak alpha gene showed a single base transition (G----A) that resulted in a glutamic acid to lysine substitution at amino acid 75 of the alpha 1 domain. This mutation confirms the importance of amino acid 75 in the expression of the Ia.19 epitope, demonstrates the involvement of this region in the presentation of antigen to specific T cells, and provides a further example of the multiple functional domains on the Ia molecule that are involved in antigen presentation.

Base Sequence↗