PubMed Health⌕ Search

Biomedical subjects

C Y Yim

Publications and source records attributed to C Y Yim.

At least 19 recordsLinked to original sources
PubMed2001

Response to high-dose intravenous immune globulin as a valuable factor predicting the effect of splenectomy in chronic idiopathic thrombocytopenic purpura patients.

This study was conducted to verify whether the response to high-dose intravenous immune globulin (IVIG) was related to the effect of splenectomy in chronic idiopathic thrombocytopenic purpura (ITP) patients. A total of 79 patients over 16 years of age were enrolled in this study. The response to the treatment was classified on the basis of the platelet count as no response (NR, <50 x 10(9)/l), incomplete response (IR, (50-150) x 10(9)/l), and complete response (CR, >150 x 10(9)/l). The response was evaluated after the infusion of high-dose IVIG, within 2 weeks after splenectomy (immediate response), and during a follow-up period of more than 6 months after splenectomy (sustained response), respectively. 58 patients (73.4%) showed responses (CR or IR) to high-dose IVIG. After splenectomy, immediate responses were observed in 73 patients (92%). The response to high-dose IVIG had no relationship with the immediate response to splenectomy (P = 0.333). A follow-up evaluation was possible with 58 patients; 6 patients with NR in immediate responses did not show any response during the follow-up period, and 17 patients relapsed within 6 months after immediate responses, so 35 patients (60.3%) had sustained responses. Responders to IVIG had significantly higher sustained response rates to splenectomy than non-responders (62% vs. 38%, P = 0.001). These results indicate that the response to high-dose IVIG could be a valuable factor predicting the sustained response to splenectomy in chronic ITP patients.

Adult↗
PubMed2000

Cytokines secreted by lymphokine-activated killer cells induce endogenous nitric oxide synthesis and apoptosis in DLD-1 colon cancer cells.

IL-2-activated killer lymphocytes (LAK cells) secrete inflammatory cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNFalpha) that can induce nitric oxide (NO) synthesis. We evaluated whether LAK cells could activate NO synthesis in human cancer cells. LAK cells and their culture supernatants induced NO synthesis in DLD-1 colon cancer cells in a dose-dependent manner. NO synthesis was inhibited completely by blocking antibodies to IFN-gamma, demonstrating a key role for this LAK cell cytokine in regulating NO synthesis. The addition of TNFalpha antibodies resulted in partial inhibition. Induction of iNOS mRNA and protein expression in DLD-1 cells was detected. Endogenous NO production inhibited DLD-1 cell proliferation and induced apoptosis, processes that were inhibitable by the NO synthase inhibitor N(G)-monomethyl-l-arginine. Our study has identified a novel, non-contact-dependent LAK cell cytotoxic mechanism: induction of growth inhibition and programmed cell death due to endogenous NO synthesis in susceptible human cancer cells.

Antigens, CD↗
PubMed2000

Interaction of two classes of ADP-ribose transfer reactions in immune signaling.

CD38 is a bifunctional ectoenzyme predominantly expressed on hematopoietic cells where its expression correlates with differentiation and proliferation. The two enzyme activities displayed by CD38 are an ADP-ribosyl cyclase and a cyclic adenosine diphosphate ribose (cADPR) hydrolase that catalyzes the synthesis and hydrolysis of cADPR. T lymphocytes can be induced to express CD38 when activated with antibodies against specific antigen receptors. If the activated T cells are then exposed with NAD, cell death by apoptosis occurs. During the exposure of activated T cells to NAD, the CD38 is modified by ecto-mono-ADP-ribosyltransferases (ecto-mono-ADPRTs) specific for cysteine and arginine residues. Arginine-ADP-ribosylation results in inactivation of both cyclase and hydrolase activities of CD38, whereas cysteine-ADP-ribosylation results only in the inhibition of the hydrolase activity. The arginine-ADP-ribosylation causes a decrease in intracellular cADPR and a subsequent decrease in Ca(2+) influx, resulting in apoptosis of the activated T cells. Our results suggest that the interaction of two classes of ecto-ADP-ribose transfer enzymes plays an important role in immune regulation by the selective induction of apoptosis in activated T cells and that cADPR mediated signaling is essential for the survival of activated T cells.

ADP-ribosyl Cyclase↗
PubMed2000

Technetium-99m MDP bone scintigraphic findings of hypercalcemia in accelerated phase of chronic myelogenous leukemia.

Hypercalcemia in accelerated phase of chronic myelogenous leukemia (CML) is very rare. Its pathogenesis is considered humoral hypercalcemia of malignancies mediated by parathyroid hormone-related protein (PTHrP). In severe hypercalcemia, calcifications in kidneys, skin, vessels, heart, and stomach may occur. Our two cases were admitted because of severe hypercalcemia in accelerated phase of CML. On Tc-99m methylene diphosphonate (MDP) bone scintigraphies, a marked tracer accumulation was seen in the lung, heart, stomach and kidney. We report increased tracer accumulation of multiple organs on Tc-99m MDP bone scintigraphy in two rare hypercalcemic patients with CML.

Adult↗
PubMed1998

Receptor-mediated activation of murine peritoneal macrophages by antithrombin III acts as a costimulatory signal for nitric oxide synthesis.

We evaluated the effect of antithrombin III (ATIII), a serine protease inhibitor (SERPIN), on induction of nitric oxide (NO) synthesis in murine peritoneal macrophages. Incubation of macrophages with ATIII plus interferon-gamma (IFN-gamma) but not ATIII alone induced nitrite accumulation (a metabolite of NO) in a dose-dependent manner. Expression of the inducible nitric oxide synthase isoform was confirmed by Western blot. NO synthesis was inhibited by NG-monomethyl-l-arginine, by complexing ATIII with thrombin or by rabbit anti-human ATIII antiserum. Addition of polymyxin B to macrophage cultures failed to inhibit ATIII/IFN-gamma-induced NO synthesis, excluding lipopolysaccharide contamination. 125I-ATIII bound to macrophages in a dose-dependent, specific, and saturable manner, with a Km of approximately 7.1 nM. Our results demonstrate that ATIII, but not ATIII/thrombin complex, acts to costimulate macrophage activation and NO synthesis via a novel receptor mediated mechanism, which may indicate a role for SERPINs in macrophage activation.

Animals↗
PubMed1998

Nitric oxide exposure inhibits induction of lymphokine-activated killer cells by inducing precursor apoptosis.

Nitric oxide synthesis is strongly induced during IL-2 treatment of mice and humans. While this free radical can act as an antitumor mechanism by inhibiting cellular respiration and DNA synthesis in cancer cells, immunosuppressive effects have also been suggested. We evaluated the effects of NO exposure on the induction of murine lymphokine-activated killer (LAK) cells from splenocytes by IL-2 (6000 IU/ml). When splenocytes were exposed to pure NO gas for 30 min prior to the addition of IL-2, complete abrogation of LAK cell cytotoxicity was observed. In contrast, cytolytic activity of already activated LAK cells was only minimally affected by NO exposure. NO exposure markedly depressed cellular proliferation in response to concanavalin A or IL-2. Immunostaining of LAK cell cultures following NO exposure revealed a marked decrease in CD8+, and peanut lectin (PNA+)/CD56+ subsets (48 and 69%). Dual staining of LAK cells for DNA strand breaks and either PNA or CD8+ identified the induction of programmed cell death in these subsets 12-24 h following NO exposure. These experiments demonstrate that NO has the capacity to inhibit LAK cell induction by inducing apoptosis of cytolytic lymphocyte precursors.

Animals↗
PubMed1997

Differences in immunophenotyping of mucosal lymphocytes between ulcerative colitis and Crohn's disease.

OBJECTIVES: Immunologic studies have characterized the numbers and types of inflammatory cells in diseased inflammatory bowel disease (IBD) mucosa but have yielded conflicting results regarding intestinal lymphocytes activation in IBD. We investigated the levels of lymphocytes subsets, interleukin-2 receptor, transferrin receptor, and T cell receptors in mainly isolated lamina propria lymphocytes. Including intraepithelial lymphocytes of normal colonic mucosa or IBD (ulcerative colitis and Crohn's disease) mucosa to understand the pathogenesis of IBD. We have results from this study. RESULTS: 1) In comparing ulcerative colitis with control, IL-2R (p < 0.05), TR (p < 0.01), and CD3/HLA-DR (< 0.05) showed a significant increase. 2) In comparing Crohn's disease with control, CD3 (P < 0.05), TCR alpha/beta (p < 0.01) and TCR gamma/delta (p < 0.05) showed a significant decrease. 3) In comparing Crohn's disease with ulcerative colitis, CD19 (p < 0.01), TR (p < 0.01), TCR alpha/beta (p < 0.01) and TCR gamma/delta (p < 0.05) showed a significant decrease. CONCLUSION: From these results, there are increased T cell markers, IL-2R, TR, and CD3/HLA-DR in UC, but differently, decreased CD3, TCR alpha/beta and TCR gamma/delta in CD compared with control. In addition, definitive differences in lymphocytes markers, CD19, TR, TCR alpha/beta and TCR gamma/delta, which are higher in UC than in CD, may elucidate the different immunopathogenesis between UC and CD.

Adult↗
PubMed1996

Effects of nitric oxide (NO) synthesis inhibition on antitumor responses during interleukin-2 (IL-2) treatment of mice.

OBJECTIVES: To evaluate if L-arginine: NO pathway is activated in tumor tissues during IL-2 therapy and to evaluate whether IL-2 induced NO synthesis represents an antitumor effector mechanism or an inhibitory factor against therapeutic effects of IL-2. METHODS: Four groups [untreated control, NG-monomethyl-L-arginine (MLA) therapy only, IL-2 therapy only, IL-2/MLA therapy groups] of BALB/c mice were injected intraperitoneally with 2 x 10(8) Meth A tumor cells on day 0. MLA was administered subcutaneously with Alzet continuous infusion pumps on day 2. IL-2 therapy (180,000 IU s.c. every 12h for 5 days) was started on day 3. NO production within ascites tumors was assessed by measuring nitrite concentrations in cultures of ascites cells harvested on day 8. Survival and the rate of body weight increment of the mice were measured to evaluate therapeutic responses. Daily urinary nitrate excretion was monitored to demonstrate the effectiveness of MLA in inhibiting NO synthesis. RESULTS: Nitrite production in supernatants of Meth A ascites cell cultures was 63 +/- 14 microM in IL-2 treated mice and 3.2 +/- 1.5 microM in untreated controls (p < 0.001). MLA prevented the IL-2 therapy induced increase in nitrite production. IL-2 therapy did not decrease the rate of body weight increment and marginally prolonged mean survival to 18.2 days, compared to 16.6 days in control mice (p = 0.255). MLA administration decreased the rate of body weight increment and prolonged mean survival of IL-2 treated mice (21.8 days, p = 0.001 versus IL-2 alone). Interestingly, the MLA treatment increased the rate of body weight increment and diminished the survival of control mice to 11.6 days (p = 0.003). MLA administration via Alzet continuous infusion pumps achieved approximately 60% suppression of urinary nitrate excretion by control mice. Subcutaneous IL-2 treatment strongly induced nitric oxide synthesis (up to 3.5 mumoles of urinary nitrate/ mouse/day). MLA also effectively suppressed IL-2 induced NO production. CONCLUSION: L-arginine: NO pathway can be activated in malignant ascites by IL-2 therapy and NO synthesis functions as an inhibitory mechanism against IL-2 induced anti-tumor effects.

Animals↗
PubMed1995

Nitric oxide synthesis contributes to IL-2-induced antitumor responses against intraperitoneal Meth A tumor.

IL-2 therapy is a potent inductive stimulus for nitric oxide (NO.) synthesis in mice and humans. It is not yet clear whether NO. can contribute to IL-2-induced therapeutic responses. The murine skin cancer Meth A is relatively resistant to lymphokine-activated killer (LAK) cell killing, allowing evaluation of the role of IL-2-induced NO. synthesis in vivo, without contribution by LAK cells. Subcutaneous IL-2 treatment of mice bearing i.p. Meth A tumor increased nitrite production by cells derived from ascites (63 +/- 14 microM vs 3.2 +/- 1.5 microM in untreated controls). N omega-monomethyl-L-arginine (MLA), NO. synthase inhibitor, prevented this increase. NO. production correlated in an inverse fashion with tumor cell proliferation in vitro. Evidence for IL-2-induced heme nitrosylation was demonstrated in tumor cells by electron paramagnetic resonance spectroscopy. By immunomagnetic depletion experiments, macrophages were implicated as a major source of NO. synthesis. Cytologic and flow-cytometric evaluation revealed that IL-2 treatment resulted in enhanced lymphocyte and macrophage recruitment into malignant ascites, and decreases in tumor cell recovery. MLA administration further increased host cell recovery. Subcutaneous IL-2 therapy increased urinary nitrate excretion up to eightfold in mice, and appeared to produce a significant survival advantage that was prevented by MLA administration.

Animals↗
PubMed1995

Effectiveness and toxicity of protracted nitric oxide synthesis inhibition during IL-2 treatment of mice.

The current study was designed to characterize nitric oxide (NO.) synthesis during interleukin-2 (IL-2) treatment of mice, and to determine whether NO. mediated IL-2-induced "vascular leak." We developed a technique for chronic subcutaneous infusion of the NO. synthase inhibitor N omega monomethyl-L-arginine (MLA) via osmotic minipump to aid in further study of these processes. After IL-2 administration to C3H/HeN mice (180,000 IU i.p. b.i.d. for 5 days), NO. synthesis increased two-to-three fold, peaking on days 5-8. Administration of MLA reduced NO. synthesis in both IL-2-treated mice (from 2.7 to 1 microM/mouse/day), and normal mice (from 1 to 0.5 microM/mouse/day). This agent decreased IL-2-induced radiolabeled albumin accumulation in the liver after i.p. IL-2 administration (p < 0.02). MLA infusions resulted in minimal systemic toxicity in mice, as reflected by complete blood counts or serum chemistries. MLA also did not impair lymphokine-activated killer cell induction in vitro or in vivo, or alter IL-2-induced tumor responses in a 3-day pulmonary metastasis model. These experiments demonstrated that NO. is a mediator involved in the genesis of vascular permeability induced by IL-2 treatment. Studies designed to further evaluate the toxicity and usefulness of MLA infusions to modify this IL-2 induced toxicity appear to be warranted.

Animals↗
PubMed1994

Use of N-acetyl cysteine to increase intracellular glutathione during the induction of antitumor responses by IL-2.

IL-2 therapy can induce marked oxidative stress via reactive oxygen and nitrogen intermediates. Glutathione, the major intracellular reductant, may become rate limiting to cytotoxic lymphocyte activation and proliferation under these circumstances. N-Acetyl cysteine (NAc-cys) was used to increase intracellular glutathione levels during lymphokine-activated killer (LAK) cell activation by IL-2. Incubation of splenocytes with NAc-cys (0.6 to 1.0 mM) resulted in significant changes in intracellular reduced and total glutathione (92% and 58% increase, respectively) at 96 h. These levels correlated with markedly enhanced cell proliferation (threefold) and cytolytic effector cell generation (> fivefold increase in LU/10(6) cells) induced by the combination of NAc-cys with IL-2. IL-2 exposure by itself unexpectedly increased intracellular reduced glutathione by 43%. IL-2 and NAc-cys were synergistic in increasing glutathione levels (reduced glutathione: 292% increase; total: 251% increase). Inhibition of glutathione synthesis, using L-buthionine-(S,R)-sulfoximine reversed the effects of NAc-cys on intracellular glutathione, as well as cellular proliferation and cytotoxicity. This experiment established that the effects of NAc-cys required de novo glutathione synthesis. In conjunction with IL-2/LAK treatment, oral NAc-cys administration (260 to 900 mg/kg/day for 7 days) significantly decreased tumor progression in a refractory s.c. tumor model. A small fraction of mice (11 to 17%) had complete tumor regressions. NAc-cys may be useful as an adjunct to increase the antitumor activity of IL-2/LAK therapy.

Acetylcysteine↗