Biomedical subjects

D H Kim

Publications and source records attributed to D H Kim.

At least 37 records · Page 2Linked to original sources

PubMed2005

Identification of glutathione conjugates and mercapturic acids of 1,2-dibromopropane in female BALB/c mice by liquid chromatography-electrospray ionization tandem mass spectrometry.

Based on recent results that 1,2-dibromopropane (1,2-DBP) causes hepatotoxicity and immunotoxicity in female BALB/c mice as well as a reduction of hepatic glutathione levels, the possible formation of glutathione conjugates and mercapturic acids of 1,2-DBP was investigated in vivo in the present studies. The following four metabolites were identified in the liver at 12 h after treatment with 1,2-DBP, by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS): M1, 2-hydroxypropylglutathione; M2, 2-oxopropylglutathione; M3, N-acetyl-S-(2-hydroxypropyl)-L-cysteine; and M4, N-acetyl-S-(2-oxopropyl)-L-cysteine. Ions of individual conjugates were observed at m/z 366, 364, 222 and 220, respectively. Characteristic product ions at m/z 237, 217, 204 and 202 for the identification of M1, M2, M3 and M4 were observed, respectively. In the sera isolated from the same animals, only mercapturic acids (M3 and M4) were observed by LC-ESI/MS. When female BALB/c mice were treated orally with 1,2-DBP at doses of 150, 300 and 600 mg kg(-1) once for 12 h, the production of glutathione conjugates and mercapturic acids in liver was apparently dose dependent, as were the concentrations of them in sera. When the production of metabolites from 1,2-DBP was investigated in liver following oral treatment with 600 mg kg(-1) 1,2-DBP for 6, 12, 24 and 48 h, metabolite concentrations were greatest at the first time point (6 h). The results explain the authors' previous studies that oral treatment with 1,2-DBP reduces the hepatic content of glutathione.

Acetylcysteine↗

PubMed2005

Monitoring of HBeAg levels may help to predict the outcomes of lamivudine therapy for HBeAg positive chronic hepatitis B.

The aim of this study was to determine whether the changing patterns of quantitative hepatitis B e antigen (HBeAg) levels by serial monitoring could predict HBeAg seroconversion and viral breakthrough during lamivudine therapy. We retrospectively analysed 340 HBeAg positive naive chronic hepatitis B patients treated with lamivudine. The mean duration of lamivudine therapy was 18.7 (range 6-56) months. The changing patterns and reduction rates of pretreatment HBeAg levels by serial monitoring were categorized into three groups: Decrescendo group (n = 195), Decrescendo-crescendo group (n = 65) and no changing or fluctuating group (n = 80). Of 109 patients who had achieved HBeAg seroconversion, 105 (96.3%) were included in the decrescendo group. The decrescendo group, pretreatment quantitative HBeAg levels, alanine aminotransferase levels, and the duration of lamivudine therapy were independent predictive factors for HBeAg seroconversion. Of 82 patients who had viral breakthrough, 53 (64.6%) were in the decrescendo-crescendo group and 21 (25.6%) were in the no changing or fluctuating group. The only predictive factor for viral breakthrough was the changing patterns of quantitative HBeAg levels, especially, the decrescendo-crescendo group and the no changing or fluctuating group. The mean time of turning points in the decrescendo-crescendo group was 7.1 months earlier than the mean time of viral breakthrough (9.0 months vs 16.5 months). Therefore, the changing patterns of quantitative HBeAg levels by serial monitoring during lamivudine therapy may allow not only the prediction of treatment responses, but also an early recognition of a viral breakthrough.

Adolescent↗

PubMed2005

Efficacy of lamivudine re-treatment for relapsed patients after an initial lamivudine therapy in HBeAg-positive chronic hepatitis B.

The efficacy of lamivudine re-treatment in chronic hepatitis B (CHB) patients who relapse after HBeAg seroconversion with lamivudine has not been investigated. The aim of this study was to evaluate the efficacy of lamivudine re-treatment in relapsed patients. Among 192 patients who had achieved HBeAg seroconversion with lamivudine at a dose of 100 mg/day, 121 patients discontinued lamivudine. Relapse occurred in 49 patients (40.5%). Thirty-three relapsed patients received lamivudine re-treatment for at least 6 months. The mean duration of lamivudine re-treatment was 16 months and the follow-up period was 8.9 months. HBeAg seroconversion was achieved in 23 patients (69.7%). The cumulative HBeAg seroconversion rates at 5, 9, and 12 months were 60, 64, and 67%, respectively. The mean time to HBeAg seroconversion in lamivudine re-treatment was shorter than that in the initial therapy (4.7 months vs. 9.7 months). Viral breakthrough occurred in six (18.2%) patients. All patients with viral breakthrough were accompanied by elevation of serum alanine aminotransferase (ALT) levels. Among 15 patients who discontinued lamivudine re-treatment after HBeAg seroconversion, relapse occurred in six patients (40%). All relapses occurred within 9 months after the discontinuation of lamivudine re-treatment. In conclusion, lamivudine re-treatment in relapsed patients after initial lamivudine therapy had a higher response rate and shorter duration to HBeAg seroconversion than during the initial therapy. However, HBeAg seroconversion induced by lamivudine re-treatment was not durable.

Adult↗

PubMed2005

Smad4 expression in gastric adenoma and adenocarcinoma: frequent loss of expression in diffuse type of gastric adenocarcinoma.

Smads are signal transducers for the members of the TGF-beta superfamily. Of these Smads, Smad4 is essential for TGF-beta signaling. The purpose of this study was to elucidate Smad4 expression and localization in 65 gastric adenomas, 49 intestinal-type and 39 diffuse type of gastric adenocarcinomas (including 12 cases of fresh frozen tissue) using Real-time RT-PCR and immunohistochemistry. Real-time RT-PCR showed that intestinal type gastric adenocarcinomas have higher Smad4 mRNA expression than diffuse type gastric adenocarcinomas. Immunohistochemical stain for Smad4 revealed that expression of Smad4 was significantly lower in diffuse-type gastric adenocarcinoma than intestinal-type gastric adenocarcinomas. Also, higher Smad4 protein expression in intestinal type gastric adenocarcinomas than overall gastric adenoma was noted. The rate of reduced Smad4 expression was higher in advanced gastric cancer than early gastric cancer. These results suggest that Smad4 might play different roles in human gastric carcinogenesis, especially between intestinal type and diffuse type of gastric adenocarcinoma.

Adenocarcinoma↗

PubMed2005

Effect of pretreatment on acid fermentation of organic solid waste.

The effect of various pretreatment methods on acidogenesis of food waste from a cafeteria was investigated. Thermal, enzymatic, and combined thermal-enzymatic batch pretreatment were conducted. Solubilization of food waste in thermal or enzymatic pretreatment increased with either increasing thermal duration or enzyme dosage, respectively. An optimal condition in thermal or enzymatic pretreatment was 60 min of thermal processing or 0.1% (v/v) of enzyme dosage level, respectively, based on volatile suspended solids (VSS) reduction. In the combined pretreatment, increased thermal duration also increased VSS reduction and the solubilization efficiency was higher than that in only enzymatic or thermal pretreatment. The maximum volatile fatty acids (VFAs) production and the highest VFAs fraction in soluble COD in the acid fermentation were achieved with the food waste after 60 min of thermal processing followed by 0.1% (v/v) enzymatic treatment. Increase in VFAs production of the fermenter was over 380% compared to the control fermenter without any pretreatment.

Acids↗

PubMed2005

Angiopoietin-1 reduces iopromide-induced endothelial cell apoptosis through activation of phosphatidylinositol 3'-kinase/p70 S6 kinase.

Radiocontrast media can induce vascular endothelial cell apoptosis. Apoptotic damage to the vascular endothelium is an important mechanism in vascular disease. Several growth factors with anti-apoptotic effects may help protect the vascular endothelium from apoptosis. The present study evaluated whether the radiocontrast agent iopromide induces apoptosis in human umbilical vein endothelial cells and also whether angiopoietin-1 (Ang1) protects against iopromide-induced apoptosis through the p70 S6 kinase-dependent signaling pathway. Iopromide induced apoptosis in vascular endothelial cells in a dose-dependent manner. Ang1 reduced iopromide-induced apoptosis in a dose-dependent manner. Wortmannin and LY294002, phosphatidylinositol 3'-kinase inhibitors, decreased the Ang1-induced anti-apoptotic effect. Ang1 mediates the activation of mTOR/ribosomal protein p70 S6 kinase through phosphatidylinositol-3' kinase. Wortmannin and rapamycin, an inhibitor of mTOR, suppressed Ang1-induced p70 S6 kinase phosphorylation and partially inhibited the Ang1-induced anti-apoptotic effect. These results suggest that Ang1 may protect vascular endothelial cells from iopromide-induced apoptosis through phosphatidylinositol 3'-kinase and mTOR/S6 kinase. Pretreatment with Ang1 could help maintain normal vascular endothelial cell integrity before and during systemic radiocontrast administration.

Analysis of Variance↗

PubMed2004

Proton source size measurements in the eA-->e'ppX reaction.

Two-proton correlations at small relative momentum q were studied in the eA(3He,4He,C,Fe)-->e(')ppX reaction at E(0)=4.46 GeV using the CLAS detector at Jefferson Lab. The enhancement of the correlation function at small q was found to be in accordance with theoretical expectations. Sizes of the emission region were extracted, and proved to be dependent on A and on the proton momentum. The size of the two-proton emission region for He was measured in eA reactions for the first time.

Journal Article↗

PubMed2004

Quantitative assessment of regional myocardial function in a rat model of myocardial infarction using tagged MRI.

We characterized global and regional left ventricular (LV) function during post myocardium infarction (MI) remodeling in rats, which has been incompletely described by previous MRI studies. To assess regional wall motion, four groups of infarcted animals corresponding to 1-2, 3-4, 6-8 and 9-12 weeks post-MI respectively were imaged using a fast gradient echo sequence with a 2D spatial modulation of magnetization (SPAMM) tagging preparation. An additional group was serially imaged (1-2 and 6-7 weeks post-MI) to assess the global function. Regional and global functional parameters of infarcted rats were compared to non-infarcted normal rats. Compared to normal rats, a decrease in ejection fraction (70 +/-7 vs. 40 +/- 8%, p<0.05) was observed in rats with MI. Maximal and minimal principal stretches (lambda1, lambda2) and strains (E1, E2), principal angle (beta) and displacement varied regionally in normal rats but deviated significantly from the normal values in rats with MI particularly in the infarcted and adjacent zones. Not only was strain magnitude reduced segmentally post-MI, but strain direction became more circumferentially oriented, particularly in rats with larger infarctions. We report the first regional myocardial strain values in normal and infarcted rats. These results parallel findings in humans, and provide a unique tool to examine regional mechanical influences on the remodeling process.

Algorithms↗

PubMed2004

Kinetic roughening of ion-sputtered Pd(001) surface: beyond the Kuramoto-Sivashinsky model.

We investigate the kinetic roughening of Ar+ ion-sputtered Pd(001) surface both experimentally and theoretically. In situ real-time x-ray reflectivity and in situ scanning tunneling microscopy show that nanoscale adatom islands form and grow with increasing sputter time t. Surface roughness W(t) and lateral correlation length xi(t) follow the scaling laws W(t) approximately t(beta) and xi(t) approximately t(1/z) with the exponents beta approximately 0.20 and 1/z approximately 0.20, for an ion beam energy epsilon=0.5 keV, which is inconsistent with the prediction of the Kuramoto-Sivashinsky (KS) model. We thereby extend the KS model by applying the coarse-grained continuum approach of the Sigmund theory to the order of O(inverted Delta(4),h(2)), where h is the surface height, and derive a new term of the form inverted Delta(2)(inverted Delta h)(2) which plays a decisive role in describing the observed morphological evolution of the sputtered surface.

Journal Article↗

PubMed2004

20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-kappaB in RAW 264.7 macrophages stimulated with lipopolysaccharide.

Ginsenosides from Panax ginseng are metabolized by human intestinal bacteria after oral administration of ginseng extract. 20(S)-Protopanaxatriol (PPT) is one of the major metabolites of ginsenosides. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important enzymes that mediate inflammatory processes. Improper up-regulation of iNOS and/or COX-2 has been associated with the pathogenesis of inflammatory diseases and certain types of human cancers. Here, we investigated whether PPT could modulate iNOS and COX-2 expressions in RAW 264.7 macrophages stimulated with the endotoxin lipopolysaccharide (LPS). We found that PPT blocked the increase in LPS-induced iNOS and COX-2 expressions through inactivation of nuclear factor-kappaB by preventing I-kappaBalpha phosphorylation and degradation. Thus, it may be possible to develop PPT as a useful agent for chemoprevention of cancer or inflammatory diseases.

Animals↗

PubMed2004

Raptor and mTOR: subunits of a nutrient-sensitive complex.

mTOR/RAFT1/FRAP is the target of the FKBP12-rapamycin complex as well as a central component of a nutrient- and hormone-sensitive pathway that controls cellular growth. Recent work reveals that mTOR interacts with a novel evolutionarily conserved protein that we named raptor, for "regulatory associated protein of mTOR." Raptor has several roles in the mTOR pathway. It is necessary for nutrient-mediated activation of the downstream effector S6K1 and increases in cell size. In addition, under conditions that repress the mTOR pathway, the association of raptor with mTOR is strengthened, leading to a decrease in mTOR kinase activity. Raptor is a critical component of the mTOR pathway that regulates cell growth in response to nutrient levels by associating with mTOR.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Hickman catheter site infections after allogeneic stem cell transplantation: a single-center experience.

Hickman catheter site infections are known to increase transplant-related mortality. A retrospective analysis of 103 patients who received allogeneic stems cell transplants was performed to define the incidence and outcomes of Hickman infections. Seventy-six patients received peripheral blood stem cells (PBSC) (73.8%) and 29 patients (28.2%) nonmyeloablative conditioning. During the median follow-up of 9 months, Hickman infections were observed in 10 patients (9.7%) at a median onset of 32 days posttransplant (range 2 to 102 days). The causative organisms identified in five cases included Staphylococcus species (n = 4) and Pseudomonas aeruginosa (n = 1). Six events successfully resolved with antibiotic treatment, while the other four required the removal of the Hickman catheter with subsequent death in two cases. The survival duration for infected patients was shorter than that for the noninfected group (83 days vs 366 days, P < .001). Myeloid engraftment was delayed in the infected group (18.0 days vs 15.0 days, P = .038) and this complication was more frequently observed among the BMT compared with PBSC group (22.2% vs 5.3%, P = .019). Hickman infections were associated with transplant-related mortality especially during the first 3 months posttransplant. As such, the current results emphasize both the importance of Hickman catheter care and the need for surveillance cultures after stem cell transplantation.

Adolescent↗

PubMed2004

Hickman catheter site infections after allogeneic stem cell transplantation: single-center experience.

Hickman catheter site infections are known to increase transplant-related mortality (TRM). A retrospective analysis of 103 patients who received allogeneic SCT (stem cell transplants) was performed to define the incidence and outcomes of Hickman infections. Seventy-six patients received peripheral blood stem cells (PBSCs) (73.8%) and 29 patients (28.2%), nonmyeloablative conditioning. During the median follow-up of 9 months, Hickman infections were observed in 10 patients (9.7%) at a median onset of 32 days posttransplantation (range, 2-102 days). The causative organisms were identified in 5 cases, including Staphylococcus species (n=4) and Pseudomonas aeruginosa (n=1). Six events were successfully resolved with antibiotic treatment, whereas the other 4 events required the removal of the Hickman catheters with subsequent death in 2 cases. The survival duration for the Hickman infection group was shorter than that for the Hickman no infection group (83 days vs 366 days, respectively; P <.001). Myeloid engraftment was delayed in the Hickman infection group (18.0 days vs 15.0 days, respectively; P=.038), plus Hickman infections were more frequent among BMT compared with PBSCT group (22.2% vs 5.3%, respectively, P=.019). Hickman infections were associated with TRM, especially during the first 3 months posttransplantation. As such, the current results emphasize both the importance of Hickman catheter care and the need for surveillance cultures after SCT.

Adolescent↗

PubMed2004

A pilot study of cytoreductive chemotherapy combined with infusion of additional peripheral blood stem cells reserved at time of harvest for transplantation in case of relapsed hematologic malignancies after allogeneic peripheral blood stem cell transplant.

Reharvesting leukocytes from donors for a donor leukocyte infusion (DLI) is inconvenient and occasionally impossible in case of unrelated donors. It is well known that the effect of a growth factor-primed DLI is comparable to that of a nonprimed DLI. In total, 42 patients with hematologic malignancies and a high risk of relapse were allocated, on an intent-to-treat basis, a peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors, and then at the time of harvest, additional peripheral blood stem cells (PBSCs) were also reserved for a therapeutic primed DLI in case of relapse. In all, 12 patients who relapsed after allogeneic PBSCT were treated with mainly cytarabine-based chemotherapy followed by a cryopreserved PBSC infusion. The median dose of CD3+ and CD34+ cells for the primed DLIs was 1.43 x 10(8)/kg and 4.75 x 10(6)/kg, respectively. Six of the 12 relapsed patients exhibited a complete response after the primed DLI, plus their 1-year survival rate was 33%. The new development or progression of graft-versus-host disease after a primed DLI was observed in 50% of the patients. Overall, the survival at 1 year was 16.7%. Accordingly, the induction of a graft-versus-leukemia effect through a primed DLI, using additional PBSCs reserved at the original time of harvest, would appear to be feasible for patients with relapsed hematologic malignancies. Furthermore, this approach is also more convenient for donors.

Adoptive Transfer↗

PubMed2004

Clinical impact of hyperacute graft-versus-host disease on results of allogeneic stem cell transplantation.

The current study defines the incidence and clinical manifestations of hyperacute graft-versus-host disease (haGVHD; fever, skin rash, diarrhea, and hepatic dysfunction) and analyzes the risk factor and the impact of haGVHD on the results of allogeneic stem cell transplantation (SCT). In all, 90 patients underwent allogeneic SCT from 71 matched siblings or 19 alternative donors. Immediate high-dose steroids were administered to 22 patients who met the criteria. The overall incidence of haGVHD was 36.7% (n=34) and haGVHD was also strongly correlated with acute (aGVHD) (P<0.001) and extensive chronic GVHD (cGVHD) (P=0.007), and found to be associated with decreased probability of relapse (P=0.0017). Early intervention with steroids within 7 days after the diagnosis of haGVHD might be associated with better survival. A survival analysis of the overall survival and disease-free survival did not reveal any difference between haGVHD+ and haGVHD- groups. In multivariate analysis, the use of an alternative donor (P=0.020) was identified as the only risk factor. Immediate high-dose steroids were effective in treating haGVHD. We conclude that in an allogeneic setting, haGVHD is not an uncommon manifestation, associated with the development of aGVHD or cGVHD. The only risk factor for haGVHD was the use of an alternative donor.

Adrenal Cortex Hormones↗

PubMed2004

Risk factors for late cytomegalovirus infection after allogeneic stem cell transplantation using HLA-matched sibling donor: donor lymphocyte infusion and previous history of early CMV infection.

An increased incidence of late cytomegalovirus (CMV) infection has been reported during the last decade since the introduction of ganciclovir (GCV) prophylaxis or GCV pre-emptive therapy. Given that a donor lymphocyte infusion (DLI) can induce more severe GVHD, this may predispose a patient to late CMV infection. In all, 64 patients (median age 36, M/F 38/26) underwent allogeneic stem cell transplantation (SCT) using a matched sibling donor with bone marrow (n=9) or peripheral blood stem cells (n=55). The overall incidence of CMV infection, early and late CMV infection was 46.9 (30/64), 42.2 (27/64), and 16.4% (9/55), respectively. Early CMV infection was treated with GCV pre-emptive therapy that produced a 92.6% success rate. Among the 20 patients who received 35 DLIs, late CMV infection developed in eight (42.1%) of 19 evaluable cases with a median onset at 127 days post transplant. Risk factors for late CMV infection in a logistic regression analysis included DLIs (P=0.001) and a previous history of CMV infection (P=0.006). In conclusion, late CMV infection was strongly associated with DLIs and a previous history of early CMV infection. Accordingly, extended surveillance of CMV antigenemia is recommended for patients receiving DLIs or who have a previous history of CMV infection.

Adult↗

PubMed2004

Transplantation outcome in allogeneic PBSCT patients according to a new chronic GVHD grading system, including extensive skin involvement, thrombocytopenia, and progressive-type onset.

Patients who had suffered chronic GVHD after an allogeneic PBSCT were evaluated using a new chronic GVHD grading system. The study included 36 consecutive adult patients with hematological diseases, who survived at least until day 90 following allogeneic PBSCT and who could be evaluated for chronic GVHD. Extensive skin involvement was observed in five patients, thrombocytopenia in 14, and progressive-type onset in 10, while grade 1 chronic GVHD appeared in 21 patients, grade 2 in 10, and grade 3 in five. There was a significant difference in the probability of relapse between the groups with grade 1 and 2+3 chronic GVHD (55.3 vs 16.4%, P=0.0211). The difference was particularly marked in patients with high-risk hematological malignancies (grade 1 vs grade 2+3, 75 vs 0%, P=0.0115). With a median follow-up of 12 months (range, 4-52 months), 22 (66.1%) patients were still alive. The estimated 2-year survival rate for the whole population was 57.6%, while that for the group with chronic GVHD grade 1 and grade 2+3 was 53.5 and 56.3%, respectively (P=0.4387). Accordingly, there was a significant difference in the probability of relapse between the groups with grade 1 and grade 2+3 chronic GVHD.

Adolescent↗

PubMed2004

Pigment-lightening effect of N,N'-dilinoleylcystamine on human melanoma cells.

BACKGROUND: Cystamine and linoleic acid have been reported to reduce melanin synthesis in vitro and in vivo. N,N'-dilinoleylcystamine (DLC) is a compound of cystamine and linoleic acid connected by an ester bond. OBJECTIVES: To investigate the effects of DLC on melanin synthesis using cultured human melanoma cells. METHODS: Levels of total melanin, eumelanin and phaeomelanin, tyrosinase protein and tyrosinase activity in situ were measured in HM3KO melanoma cells. Changes in degree of pigmentation were quantified by image analysis and compared with absorbance values. Tyrosinase from HM3KO cells was used to measure the direct effect of DLC on DOPA and DOPAchrome production. RESULTS: At concentrations of 1.4-14 micromol L-1, DLC reduced the pigmentation of HM3KO melanoma cells but did not affect cell growth. The visual decrease in pigmentation produced by DLC was more dramatic than the decrease in total melanin content as measured by absorbance at 500 nm. DLC treatment decreased eumelanin synthesis and increased phaeomelanin synthesis in HM3KO melanoma cells. An in situ tyrosinase assay showed that DLC inhibited tyrosinase activity, as well as the level of tyrosinase protein. CONCLUSIONS: These results suggest that DLC has pigment-lightening effects on HM3KO melanoma cells, produced by reducing the level of eumelanin while increasing the level of phaeomelanin.

Blotting, Western↗