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Biomedical subjects

Y Choi

Publications and source records attributed to Y Choi.

367 records · Page 21Linked to original sources

Unresponsiveness to surface antigen 1 modifies cytokine profiles in acute Toxoplasma gondii infection.

Resistance to Toxoplasma gondii involves the development of a highly polarized Th1-type cytokine expression. SAG1 transgenic mice are highly susceptible to T. gondii infection due to their non-reactivity to SAG1 of the protozoan parasite. Here we describe cytokine profiles during the acute phase of T. gondii infection, which are associated with the susceptibility of SAG1 transgenic mice. SAG1 transgenic mice showed a 4.5-fold increase in susceptibility upon inoculation with a sublethal dose of the Beverley strain of T. gondii compared to their wild-type counterparts (mortality: 81 vs. 18%, respectively). When analysis of the most important cytokines involved in the mediation of resistance to infection was carried out, SAG1 transgenic mice exhibited low production levels of IL-12, IFN-gamma and TNF-alpha in sera during the acute phase of T. gondii infection. Antibody and T cells specific for SAG1 were not mounted upon SAG1 stimulation in SAG1 transgenic mice. Moreover, in vitro studies indicated that in SAG1 transgenic mice IFN-gamma and IL-12 production was lower than in their wild-type counterparts, although levels of TNF-alpha increased in SAG1 transgenic mice on day 9 after infection. Low IgG2a levels were detected in SAG1 transgenic mouse sera. Unresponsiveness to SAG1 of T. gondii renders SAG1 transgenic mice unable to develop a strong Th1-based protection against T. gondii infection. These results provide evidence that SAG1 is a pivotal antigen involved in the induction of immune responses towards the development of Th1-protective immunity during T. gondii infection.

Animals↗

The endoplasmic reticulum chaperone GRP94 is induced in the thyrocytes by cadmium.

We established a relationship between the toxic effects of cadmium on the expression of the endoplasmic reticulum (ER) chaperone GRP94 (glucose regulated protein 94) and cell survival in cultured rat-thyrocytes of FRTL5 cells. There are no data reporting that the enhanced expression of GRP94 by Cd stimulation is detectable in thyrocytes. Western blot analysis revealed higher levels of GRP94 expression in those cells post-treated with low concentrations of Cd, following a step-down treatment method, than in Cd pre-treated cells or cells not treated with any Cd, due to changes in cellular sensitivity after pre-treatment with Cd and the possible induction of GRP94 expression after removal of a low concentration of Cd. Elevated GRP94 expression in thyrocytes post-treated with Cd confers a survival advantage by rendering them resistant to cytotoxic stress, and the existence in the thyrocytes of a Cd-specific pathway regulates the expression of stress proteins by Cd.

Cadmium↗

Identification of genes in a thyroid cell line regulated by thyroid-stimulating hormone (TSH).

Differential display (DD) PCR (Liang and Pardee, 1992) is a recently described technique to identify genes whose expression has changed during a biological process. We used this method to detect genes thyroid stimulating hormone-dependently regulated in a rat thyroid cell line, because thyroid stimulating hormone (TSH) is the most important hormone for cell proliferation and differentiation including prehormonal proteins secretion in thyrocytes (Kim and Arvan, 1991; Kim and Arvan, 1993). Following DD-PCR experimentation, thyroid stimulating hormone-dependently regulated gene fragments of 15 species were obtained. The genes were used as molecular probes in Northern blot analysis and then sequenced. Two of the clones (#123 and #205) were up-regulated and two more (#107 and #111) were down-regulated thyroid stimulating hormone-dependently in the thyroid cells, as demonstrated by Northern blot analysis. Following partial sequencing, each of the clones #107, #111 and #205 were shown to be homologues of the apoptosis-related gene, aldolase A, and a-2 collagen (IV), respectively, while clone #123 showed no homology with known genes. These findings suggest that the four genes mentioned above may have an a important physiological function in the thyrocytes, which is thyroid stimulating hormone-dependently up-/down-regulated.

Animals↗

Inhibition of chemokine-induced chemotaxis of monkey leukocytes by mu-opioid receptor agonists.

It is recognized that chemotaxis and phagocytosis constitute the first line of defense in the immune system, and chemokines function mainly as chemoattractants for phagocytic cells, recruiting monocytes and neutrophils from the blood to sites of infection. In this study, chemotaxis of monkey leukocytes was evaluated using human chemokines IL-8 (interleukin-8), MIP-1 beta and RANTES as the chemoattractants, and the effects of micro-opioid receptor agonists, morphine, DAMGO, methadone and endomorphine, on the efficiency of chemotaxis were examined. It was found that human chemokines served well as chemoattractants for monkey leukocytes, and similar to the human system, chemokine-induced chemotaxis of monkey leukocytes was inhibited in the presence of micro-opioid receptor agonists. The inhibition could be reversed by naloxone, a specific micro-opioid receptor antagonist. These studies further support the value of the monkey model for drug abuse studies in humans, as well as suggest that opioids such as morphine may alter immune functions through micro-opioid receptors on leukocytes.

Analgesics, Opioid↗

Circulating VEGF and TGF-beta1 in children with idiopathic nephrotic syndrome.

RATIONALE: The implications of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-beta) on the development of proteinuria were studied by measuring the mRNA and protein levels of VEGF and TGF-beta1 in 43 children with primary nephrotic syndrome. METHODS: Twenty-seven patients were in the active nephrotic phase at the time of sampling (Group 1), and 16 were in remission (Group 2). In Group 1, 16 were steroid-responders (Group 1a) and 11 were nonresponders (Group 1b). Minimal change lesion (MCL) in 11 patients and focal segmental glomerulosclerosis (FSGS) in 8 were confirmed by renal biopsy. The mRNA expressions of peripheral blood lymphocytes and the plasma levels of proteins were measured by semi-quantitative RT-PCR and ELISA, respectively. RESULTS: Plasma VEGF concentration was higher in Group 1 (204+/-137 pg/mL) than Group 2 (91+/-72 pg/mL) (P=0.002). However, there was no significant difference either between Group 1a (184+/-146 pg/mL) and Group 1b (258+/-134 pg/mL) or between patients with FSGS (330+/-122 pg/mL) and those with MCL (146+/-112 pg/mL). The VEGF mRNA expression showed changes similar to VEGF protein expression, and there was no statistical significance. Plasma levels and mRNA expressions of TGF-beta1 were similar in all groups. CONCLUSIONS: These results suggest that circulating VEGF is associated with proteinuria both in steroid-responsive and steroid-resistant primary nephrotic syndrome in children.

Adolescent↗

Necrotizing arteriolitis of ileum, as the initial manifestation of malignant hypertension in childhood.

Intestine is seldom a site of clinical manifestation of malignant hypertension, particularly in childhood. This report deals with a case of malignant nephrosclerosis superimposed on benign nephrosclerosis which probably resulted from a unilateral obstructive uropathy and chronic pyelonephritis. Clinical features included severe hypertension, neuroretinopathy with retinal exudate and hypertensive encephalopathy. An acute abdomen due to transmural infarction of the ileum caused by multiple thrombotic occlusion of necrotizing arteritis involving bowel wall and the mesentery was noted.

Arterioles↗

Soluble IL-2 receptor beta and gamma subunits: ligand binding and cooperativity.

Biologically relevant interleukin-2 receptors (IL-2Rs) are present in two affinity states on responsive cells. High affinity receptors (HAR) apparently exist as heterotrimers (alpha, beta and gamma) while the other functional complex, the intermediate affinity receptor (IAR), is comprised of beta and gamma chains. The mechanisms by which the beta and gamma subunits contribute the formation of HAR and IAR are still unclear. Soluble forms of the beta and gamma chains were cloned, epitope-tagged, expressed in insect cells and purified. IL-2 binding and neutralization of IL-2 bioactivity by beta and gamma extracellular domains (ectodomains) was analyzed by several biochemical and biological approaches. The results indicate that beta clearly binds IL-2 with low affinity (KI-KD = 3 microM) whereas gamma binding is detectable, but of very low affinity (apparent KI > 15 microM) in the absence of beta. Interestingly, combinations of beta and gamma ectodomains interact to bind IL-2 with higher affinity and greater stability than either chain alone. An apparent stable binding complex is formed when beta, gamma, and IL-2 are combined. Ligand binding by the beta and gamma chains in solution is specific for IL-2 and is of sufficient affinity and stability to effectively neutralize IL-2 in biological assays (binding IC50 = biological IC50). Direct analyses of binding kinetics by surface plasmon resonance reveals that the increased affinity and biological neutralizing ability of beta gamma, as compared to beta, is due to a very slow dissociation rate contributed by the gamma ectodomain. While IL-2R beta and gamma cytoplasmic and transmembrane domains are not essential for interactive binding of IL-2, they may contribute to IL2 binding affinity. The recognition and association of IL-2 by the beta gamma IAR appears to be contributed primarily by the beta chain while the stability and dissociation is likely dominated by the gamma chain. It is anticipated that the gamma subunit functions in a similar manner when participating in high affinity IL-4 and IL-7 binding.

Binding, Competitive↗