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Biomedical subjects

J K Choi

Publications and source records attributed to J K Choi.

At least 37 records · Page 2Linked to original sources

Inhibition of natural killer cell-mediated cytotoxicity by Kaposi's sarcoma-associated herpesvirus K5 protein.

Kaposi's sarcoma-associated herpesvirus (KSHV) K3 and K5 proteins dramatically downregulate MHC class I molecules. However, although MHC class I downregulation may protect KSHV-infected cells from cytotoxic T lymphocyte recognition, these cells become potential targets for natural killer (NK) cell-mediated lysis. We now show that K5 also downregulates ICAM-1 and B7-2, which are ligands for NK cell-mediated cytotoxicity receptors. As a consequence, K5 expression drastically inhibits NK cell-mediated cytotoxicity. Conversely, de novo expression of B7-2 and ICAM-1 resensitizes the K5-expressing cells to NK cell-mediated cytotoxicity. This is a novel viral immune evasion strategy where KSHV K5 achieves immune avoidance by downregulation of cellular ligands for NK cell-mediated cytotoxicity receptors.

Antigens, CD↗

Quantitative analysis of eotaxin and RANTES messenger RNA in nasal polyps: association of tissue and nasal eosinophils.

OBJECTIVES/HYPOTHESIS: Nasal polyps develop in the ethmoidal and middle turbinate area, often in relation to inflammatory conditions. Their exact etiology and pathogenesis are still under debate. Histologically, the polyps are infiltrated by a number of inflammatory cells, with eosinophil predominating in most specimens. This finding suggests that the nasal polyp is an inflammatory growth that is controlled by the local environment. The chemokines eotaxin and RANTES (regulated on activation normal T cell expressed and secreted) have been postulated to be involved in the recruitment and activation of eosinophils to certain inflamed tissues. The purpose of this study was to investigate eotaxin and RANTES mRNA expression in nasal polyps and its effect on tissue and nasal eosinophils. METHODS: Nasal polyps (917 allergic and 30 nonallergic cases) were obtained from endoscopic sinus surgery, and 15 normal inferior turbinates also were taken. Immunohistochemical staining for eosinophils and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) tests for eotaxin and RANTES mRNA expression were performed, and the concentration of nasal eosinophil cationic protein (ECP) was measured. RESULTS: The amounts of eotaxin mRNA in the allergic nasal polyps were 11.4 times higher and the levels in the nonallergic polyps were 6.4 times higher than in the normal inferior turbinate. However, the RANTES mRNA expression did not show any differences among the three groups. Tissue eosinophilia and nasal ECP levels were significantly correlated with eotaxin mRNA level but not with RANTES mRNA expression. CONCLUSION: Nasal polyp eosinophilic infiltration and activation correlate mainly with increased eotaxin gene expression rather than with RANTES expression.

Adolescent↗

The collagen repeat sequence is a determinant of the degree of herpesvirus saimiri STP transforming activity.

Herpesvirus saimiri (HVS) is divided into three subgroups, A, B, and C, based on sequence divergence at the left end of genomic DNA in which the saimiri transforming protein (STP) resides. Subgroup A and C strains transform primary common marmoset lymphocytes to interleukin-2-independent growth, whereas subgroup B strains do not. To investigate the nononcogenic phenotype of the subgroup B viruses, STP genes from seven subgroup B virus isolates were cloned and sequenced. Consistent with the lack of oncogenic activity of HVS subgroup B viruses, STP-B was deficient for transforming activity in rodent fibroblast cells. Sequence comparison reveals that STP-B lacks the signal-transducing modules found in STP proteins of the other subgroups, collagen repeats and an authentic SH2 binding motif. Substitution mutations demonstrated that the lack of collagen repeats but not an SH2 binding motif contributed to the nontransforming phenotype of STP-B. Introduction of the collagen repeat sequence induced oligomerization of STP-B, resulting in activation of NF-kappaB activity and deregulation of cell growth control. These results demonstrate that the collagen repeat sequence is a determinant of the degree of HVS STP transforming activity.

Amino Acid Motifs↗

Identification of the novel K15 gene at the rightmost end of the Kaposi's sarcoma-associated herpesvirus genome.

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a distinct open reading frame called K15 at a position equivalent to the gene encoding LMP2A of Epstein-Barr virus (EBV). K15 isolates from body cavity-based lymphoma (BCBL) cells exhibited a dramatic sequence variation and a complex splicing pattern. However, all K15 alleles are organized similarly with the potential SH2 and SH3 binding motifs in their cytoplasmic regions. Northern blot analysis showed that K15 was weakly expressed in latently infected BCBL-1 cells, and the level of its expression was significantly induced by tetradecanoyl phorbol acetate stimulation. K15 encoded 40- to 55-kDa proteins, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and was localized at the cytoplasm and plasma membrane. To demonstrate the signal-transducing activity of the K15 protein, we constructed a chimeric protein in which the cytoplasmic tail of the human CD8alpha polypeptide was replaced with that of KSHV K15. While the CD8-K15 chimera was not capable of eliciting cellular signal transduction upon stimulation with an anti-CD8 antibody, it significantly inhibited B-cell receptor signaling, as evidenced by a suppression of tyrosine phosphorylation and intracellular calcium mobilization. This inhibition required the putative SH2 or SH3 binding motif in the cytoplasmic region of K15. Biochemical study of CD8-K15 chimeras showed that the cytoplasmic region of K15 was constitutively tyrosine phosphorylated and that the tyrosine residue within the putative SH2 binding motif of K15 was a primary site of phosphorylation. These results demonstrate that KSHV K15 resembles LMP2A in genomic location, splicing pattern, and protein structure and by the presence of functional signal-transducing motifs in the cytoplasmic region. Thus, KSHV K15 is likely a distant evolutionary relative of EBV LMP2A.

Alleles↗

Synthesis and pharmacological profile of 1-aryl-3-substituted pyrrolo[3,2-c]quinolines.

A series of 1-aryl-3-substituted pyrrolo[3,2-c]quinolines were synthesized and evaluated for their anti-ulcer activity. While 3-substituents of pyrrolo[3,2-c]quinolines mostly affected the in vitro H+/K+ ATPase activity, 1-aryl substituents of pyrrolo[3,2-c]quinolines affected the in vivo gastric acid secretion. In addition, the compounds with good in vivo activity protected from ethanol-induced ulcer.

Animals↗

Increased expression of CaM kinase II alpha in the brains of scrapie-infected mice.

We investigated the distribution of calcium/calmodulin-dependent protein kinase II (CaM kinase II) in the brains of mice infected with ME7 scrapie strain. CaM kinase II is an enzyme that plays a major role in the regulation of long-term potentiation, a form of synaptic plasticity associated with learning and memory. Immunoreactivity of CaM kinase II alpha, measured by Western blot, increased markedly in scrapie-infected brains compared with control brains. Immunohistochemically, CaM kinase II alpha immunoreactivity was upregulated in the cerebral cortex and hippocampal CA1 area of scrapie-positive mice infected with ME7 scrapie strain. This result implies that this enzyme is associated with aberrant function of synaptic transmission and LTP of the pyramidal neurons in the hippocampal CA1 area of mice infected with ME7 scrapie strain.

Animals↗

Detection of DNA in agarose gels using berberine and Mordant Yellow 3R.

A nontoxic and simple staining method for the detection of DNA in agarose gels is described. After eletrophoretic separation, the gels were stained with 5 microg/ml of berberine (BB) prepared in distilled water and then the gels were soaked in 20 microg/ml of aqueous Mordant Yellow 3R (MY3R) solution. Employment of MY3R as a counterion dye efficiently quenched unwanted background fluorescence of BB. This method can detect as little as 10 ng of plasma membrane H(+)-ATPase cDNA obtained from Arabidopsis thaliana L. (AHA1, 3.2 kb) under a long wavelength of UV irradiation (366 nm) within 1 h.

Arabidopsis↗

Nucleotide sequence analysis of the 3'-terminal region of two Korean isolates of lily symptomless Carlavirus and expression of the coat protein in E. coli.

The 3'-terminal regions of the genomic RNAs of two Korean isolates of the lily symptomless Carlavirus (LSV), LSV-Ko and LSV-KII, were cloned and their nucleotide sequences were determined. The nucleotide sequence analysis and protein analysis by the Western blot revealed that E. coli expressed a 32-kDa protein that is the viral coat protein (CP) for the LSV. The two Korean strains share 98.4% and 98.3% sequence identities at the nucleotide and amino acid levels, respectively. The CP gene of LSV-Ko showed 99.1% and 87.0% nucleotide sequence identities, and 99.0% and 96.6% amino acid sequence identities with those of the Netherlands and the Japanese LSV strains, respectively. A pairwise amino acid sequence comparison revealed a sequence similarity of 29.6% to 69.8% between LSV-Ko and other species of the carlavirus. The 16 kDa protein of LSV-Ko shares 17.6% to 42.7% amino acid similarity with those of 8 other the carlaviruses, and they are variable in the N-terminal region. The Cys repeated zinc finger nucleic acid binding domain was found in the 16 kDa protein for all of the LSV strains. Sequence comparisons of the 7 kDa protein of LSV in the strain level showed significant identities from 100.0% to 98.4%. LSV-Ko shares 21.9% to 42.2% amino acid similarity with those of 8 other carlaviruses, 4 members of the potexviruses, and a closterovirus. LSV is closely related to blueberry scorch virus (BISV) based upon the phylogenetic tree analyses of the three proteins, indicating LSV to be a quite distinct member of the genus Carlavirus.

Amino Acid Sequence↗

Herpesvirus saimiri as a model for gammaherpesvirus oncogenesis.

Herpesvirus saimiri (HVS) causes T-lymphoproliferative dis-$borders in several New World and Old World primate species and in certain rabbits.In vitro infection leads to permanent growth of primary T cells of primate and human origins. The transformation-relevant proteins of HVS interact with cellular proto-oncoproteins which results in cell growth transformation. In addition, virus-encoded cellular homologues may contribute to transformation or persistence of HVS by altering cellular signal transduction and deregulating cell growth control. Because of the presence of a permissive cell culture system and in vitro Land in vivo transformation assays, HVS provides a unique opportunity to investigate the mechanisms of cancer induction by oncogenic herpesviruses.

Animals↗

Incorporation of [1-13C]oleate into cellular triglycerides in differentiating 3T3L1 cells.

Oleate is one of the most abundant dietary fatty acids, and much remains to be learned about its metabolism in fat cells. We studied the incorporation of exogenous [1-13C]oleate into triglycerides (TG) in differentiating 3T3L1 preadipocytes using 13C NMR spectroscopy. The quantity of oleate incorporated into TG was found to increase as preadipocytes differentiated into fat cells. The ratio of unesterified [1-13C]oleate to total stored fatty acids was higher in less differentiated cells, and declined at later stages of differentiation as cells accumulated fatty acids through de novo synthesis. When added as the only exogenous fatty acid, oleate was largely esterified at the sn-2 position. When equimolar unlabeled linoleate was co-provided at the same time, the ratio of [1-13C]oleate esterified at the sn-1,3 position increased, implying competition between linoleate and oleate for esterification, especially at the sn-2 position. When cells pre-enriched with [1-13C]oleate (esterified to TG) were treated with isoproterenol, a lipolytic agent, most of the [1-13C]oleate was still found in TG, despite a high rate of lipolysis determined by measuring glycerol release. This implies extensive re-esterification of the oleate released by lipolysis.

3T3 Cells↗

RT-PCR detection and identification of three species of cucumoviruses with a genus-specific single pair of primers.

Reverse transcription and polymerase chain reaction (RT-PCR) was used for detection and identification of three cucumoviruses (cucumber mosaic virus, CMV; peanut stunt virus, PSV; tomato aspermy virus, TAV) in various plants sources with a single pair of primers, designed as CPTALL-3 and CPTALL-5. The pair of cucumovirus genus-specific primers that flank the coat protein gene were designed and used to amplify a DNA fragment of approximately ranging from 938 to 966 bp. The RT-PCR with the set of primers specifically amplified the target size of DNA fragment in all the tested cucumoviruses (CMV S-IA, S-IB and S-II, PSV and TAV). No DNA product of any length was produced when brome mosaic virus or tobacco mosaic virus RNA was used as templates. The cucumoviruses examined were differentiated by PCR-restriction fragment length polymorphism with different enzymes. This indicates that the designed primers are only specific for the cucumoviruses and useful for reliable information of identification of members of the Cucumovirus genus.

Base Sequence↗

Role of cellular tumor necrosis factor receptor-associated factors in NF-kappaB activation and lymphocyte transformation by herpesvirus Saimiri STP.

The STP oncoproteins of the herpesvirus saimiri (HVS) subgroup A strain 11 and subgroup C strain 488 are now found to be stably associated with tumor necrosis factor receptor-associated factor (TRAF) 1, 2, or 3. Mutational analyses identified residues of PXQXT/S in STP-A11 as critical for TRAF association. In addition, a somewhat divergent region of STP-C488 is critical for TRAF association. Mutational analysis also revealed that STP-C488 induced NF-kappaB activation that was correlated with its ability to associate with TRAFs. The HVS STP-C488 P10-->R mutant was deficient in human T-lymphocyte transformation to interleukin-2-independent growth but showed wild-type phenotype for marmoset T-lymphocyte transformation in vitro and in vivo. The STP-C488 P10-->R mutant was also defective in Rat-1 fibroblast transformation, and fibroblast cell transformation was blocked by a TRAF2 dominant-negative mutant. These data implicate TRAFs in STP-C488-mediated transformation of human lymphocytes and rodent fibroblasts. Other factors are implicated in immortalization of common marmoset T lymphocytes and may also be critical in the transformation of human lymphocytes and rodent fibroblasts.

Amino Acid Sequence↗

Identification of the R1 oncogene and its protein product from the rhadinovirus of rhesus monkeys.

Rhesus monkey rhadinovirus (RRV) is a gamma-2 herpesvirus that is most closely related to the human Kaposi's sarcoma-associated herpesvirus (KSHV). We have identified a distinct open reading frame at the left end of RRV and designated it R1. The position of the R1 gene is equivalent to that of the saimiri transforming protein (STP) of herpesvirus saimiri (HVS) and of K1 of KSHV, other members of the gamma-2 or rhadinovirus subgroup of herpesviruses. The R1 sequence revealed an open reading frame encoding a product of 423 amino acids that was predicted to contain an extracellular domain, a transmembrane domain, and a C-terminal cytoplasmic tail reflective of a type I membrane-bound protein. The predicted structural motifs of R1, including the presence of immunoreceptor tyrosine-based activation motifs, resembled those in K1 of KSHV but were distinct from those of STP. R1 sequences from four independent isolates from three different macaque species revealed 0.95 to 7.3% divergence over the 423 amino acids. Variation was located predominantly within the predicted extracellular domain. The R1 protein migrated at 70 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was extensively glycosylated. Tagged R1 protein was localized to the cytoplasmic and plasma membranes of transfected cells. Expression of the R1 gene in Rat-1 fibroblasts induced morphologic changes and focus formation, and injection of R1-expressing cells into nude mice induced the formation of multifocal tumors. A recombinant herpesvirus in which the STP oncogene of HVS was replaced by R1 immortalized T lymphocytes to interleukin-2-independent growth. These results indicate that R1 is an oncogene of RRV.

Amino Acid Sequence↗

Hyperacute rejection of a pulmonary allograft. Immediate clinical and pathologic findings.

The clinical and pathologic findings seen in hyperacute rejection are well documented in renal and cardiac allografts. We describe the second case of hyperacute rejection in a pulmonary allograft and detail the immediate clinicopathologic findings. The patient underwent a single lung transplant for severe COPD with postoperative course complicated by acute rejection and graft failure. Eleven days later, the patient underwent a second transplant with intra-operative course complicated by rapid pulmonary edema and copious production of frothy, pink fluid from the bronchial orifice of the allograft followed by death within four hours of anastomoses. Intraoperative biopsy and autopsy demonstrated platelet/fibrin thrombi, marked interstitial neutrophilia, alveolar edema, and antibody deposition on the endothelial surface and vasculature walls. Prior to the first transplant, the patient's serum had 0% panel reactive antibody and was crossmatch compatible with the first allograft. The patient's serum prior to the second transplant contained cross-reacting antibodies to the donor's B and T lymphocytes. The immediate clinical findings in this case are similar to the findings in a previously reported case. This report is the first documentation of the immediate pathologic features of hyperacute rejection in a lung allograft which are similar to those seen with other organ allografts.

Fatal Outcome↗

Cardiovascular regulation during water immersion.

Head-out water immersion at thermoneutral temperature (34-35 degrees C) increases cardiac output for a given O2 consumption, leading to a relative hyperperfusion of peripheral tissues. To determine if subjects immersed in water at a colder temperature show similar responses and to explore the significance of the hyperperfusion, cardiovascular functions were investigated (impedance cardiography) on 10 men at rest and while performing exercise on a leg cycle ergometer (delta M = approximately 95 W.m-2) in air and in water at 34.5 degrees C and 30 degrees C, respectively. In subjects resting in water, the cardiac output increased by approximately 50% compared to that in air, mainly due to a rise in stroke volume. The stroke volume change tended to be greater in 30 degrees C water than in 34.5 degrees C water, and this was due to a greater increase in cardiac preload, as indicated by a significantly greater left ventricular end-diastolic volume. Arterial systolic pressure rose slightly during water immersion. Arterial diastolic pressure remained unchanged in 34.5 degrees C water, but it rose in 30 degrees C water. The total peripheral resistance fell 37% in 34.5 degrees C water and 32% in 30 degrees C water. Both in air and in water, mild exercise increased the cardiac output, and this was mainly due to an increase in heart rate. Since, however, the stroke volume increased with water immersion, cardiac output at a given work load appeared to be significantly higher in water than in air. The arterial pressures did not decrease with water immersion, despite a marked reduction in total peripheral resistance. These results suggest that 1) during cold water immersion, peripheral vasoconstriction provides an additional increase in cardiac preload, leading to a further increase in the stroke volume compared to that of the thermoneutral water immersion, 2) the mechanism of cardiovascular adjustment during dynamic exercise is not changed by the persistent increase in cardiac preload in water immersion, and 3) a relatively high cardiac output during water immersion is to maintain a proper arterial pressure in the face of reduced vascular resistance.

Adult↗

[Possibility in unification of oriental and western medicine education by combination of educational curricula].

The authors attempted a possibility of unification in the educational curricula of both Oriental and Western medical schools for the unification of two medicines. Historically the two medicines were originated from the most primitive state like instinctive method and we can say two medicines were entirely the same. However, after abrupt and current development of science in the 19th century by discovery of microscope and bacteria as well as cells, changed medicine into recent unbelievable current medicine from old ancient style medicine like Chinese Medicine which was just the remnant old medicine. The unification of educational curricula is thought to be possible to combine each other by technical adjustment from mutual understanding and cooperation for the most high quality of peoples lives. There were good equality to partial correspondences between two educational curricula around 90% at two pre-and schools from the study to analyse. The combined medicine is thought to be more efficient to the diagnosis and treatment of patients because of the effectiveness of Oriental medicine in certain disease conditions like chronic illness by acupuncture as a alternative medicine or herbs.

Curriculum↗