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Biomedical subjects

C C Kim

Publications and source records attributed to C C Kim.

At least 19 recordsLinked to original sources
PubMed2006

Vascular endothelial growth factor (VEGF) is associated with reduced severity of acute graft-versus-host disease and nonrelapse mortality after allogeneic stem cell transplantation.

This study investigated whether or not there is a correlation between the changes in the serum levels of vascular endothelial growth factor (VEGF) and the outcome of allogeneic stem cell transplantation (allo-SCT). Eighty-five patients undergoing allo-SCT were prospectively studied. The serum VEGF levels were measured on days 0, +7 and +14 after transplantation. The VEGF levels decreased significantly on day +7 and recovered on day +14. The highest levels from day +7 through day +14 were categorized by cluster analysis, which were then correlated with the nonrelapse mortality (NRM). There was a significant correlation between a low VEGF level and the occurrence of severe acute graft-versus-host disease (GVHD) including grade III-IV (P=0.029). The 1-year probability of NRM in patients with a low VEGF level was 22.5% compared with 3.5% for those with a high VEGF level (P=0.024). Multivariate analysis revealed clinically defined infections (P=0.011), advanced disease (P=0.014) and a low VEGF cluster (P=0.05) to be significantly associated with the occurrence of NRM in the cohort. In conclusion, low VEGF levels after allo-SCT are associated with NRM with an exacerbated severity of acute GVHD. VEGF monitoring after a transplant might identify those patients at risk of severe transplant-related mortality.

Acute Disease↗
PubMed2006

Patterns of C-reactive protein release following allogeneic stem cell transplantation are correlated with leukemic relapse.

The C-reactive protein (CRP) is an acute-phase protein produced by hepatocytes, and is a reliable marker of systemic inflammation, which is relevant to the release of the proinflammatory cytokines. The value of monitoring the CRP levels after stem cell transplantation (SCT) can identify patients at risk of treatment-related complications and mortality. Inflammatory cytokines facilitate donor T-cell activation via antigen presenting cells immediately after SCT. This study examined the relationship between the post-SCT CRP levels and a leukemic relapse. Fifty-four consecutively transplanted patients who relapsed after the allogeneic SCT were compared with nonrelapsing patients. The serum CRP levels were measured on day 0 and every 7 days thereafter until 4 weeks after the SCT. The mean CRP levels throughout the early post-SCT episode were significantly lower in the relapsing patients than in those who did not experience relapse (mean+/-s.e.: 26.8 +/- 6.3 vs 65.3 +/- 9.4 for first week, P = 0.001; 23.9 +/- 3.8 vs 44.6 +/- 6.6 for second week, P = 0.008). Univariate analysis showed that the CRP level on the first and second week, and graft-versus-host disease were significantly associated with a relapse. Multivariate analysis showed that the CRP level on the first week was the strongest independent variable predicting the risk of a relapse after SCT (P = 0.04). These results indicate that the serum CRP levels early after allogeneic SCT might display the graft-versus-leukemia (GvL) effect. CRP is a surrogate of the proinflammatory cytokine release that was not measured in this study. The GvL effect appears to be efficiently strengthened by the high CRP levels that may be reflecting T-cell activation.

Adolescent↗
PubMed2005

Impact of ABO incompatibility on outcome after allogeneic peripheral blood stem cell transplantation.

Few studies have addressed the incidence of graft-versus-host disease (GVHD) or survival after ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT). We analyzed the clinical outcome of ABO incompatibility after allogeneic PBSCT. A total of 89 consecutive adult patients with hematological diseases including 49 ABO-identical, 20 major, 15 minor, and five bidirectional ABO-incompatible transplants were enrolled from four medical centers in Korea. No significant difference in engraftment times, graft failure, or transfusion requirements between groups was noted. A clinical diagnosis of severe immune hemolysis or pure red cell aplasia was not made for any patient after transplantation. The incidence of acute or chronic GVHD did not statistically differ between groups. With a median follow-up duration of 13 months (range, 0.5-61 months), the 3-year overall survival estimates for the ABO-identical, major/bidirectional, and minor group were 44.6.0+/-9.0, 43.1+/-11.6, and 43.8+/-13.5%, respectively (P=0.8652), while the 3-year disease-free survival estimates were 33.8+/-7.6, 39.9+/-11.4, and 45.7+/-13.1%, respectively (P=0.8546). We observed that time to neutrophil, platelet, and red blood cell engraftment, transfusion requirements, incidence of acute or chronic GVHD, relapse, and survival were not influenced by ABO incompatibility after allogeneic PBSCT from HLA-matched sibling donors.

ABO Blood-Group System↗
PubMed2004

Imaging cells and tissues with refractive index radiology.

Can individual cells, including live cells, be imaged using hard x rays? Common wisdom until now required sophisticated staining techniques for this task. We show instead that individual cells and cell details can be detected in culture solution and tissues with no staining and no other contrast-enhancing preparation. The sample examined can be much thicker than for many other microscopy techniques without sacrificing the capability to resolve cells. The key factor in our approach is the use of a coherent synchrotron source and of contrast mechanisms based on the refractive index. The first successful tests were conducted on a variety of cell systems including skin and internal leaf cells, mouse neurons, rabbit fibroblast cells, and human tumor cells.

Animals↗
PubMed2004

A novel splice acceptor mutation in the DSPP gene causing dentinogenesis imperfecta type II.

The dentin sialophosphoprotein (DSPP) gene (4q21.3) encodes two major noncollagenous dentin matrix proteins: dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Defects in the human gene encoding DSPP cause inherited dentin defects, and these defects can be associated with bilateral progressive high-frequency sensorineural hearing loss. Clinically, five different patterns of inherited dentin defects are distinguished and are classified as dentinogenesis imperfecta (DGI) types I, II, and III, and dentin dysplasia types I and II. The genetic basis for this clinical heterogeneity is unknown. Among the 11 members recruited from the studied kindred, five were affected with autosomal dominant DGI type II. The mutation (g.1188C-->G, IVS2-3C-->G) lay in the third from the last nucleotide of intron 2 and changed its sequence from CAG to GAG. The mutation was correlated with the affection status and was absent in 104 unaffected individuals (208 alleles) with the same ethnic and geological background. The proband was in the primary dentition stage and presented with multiple pulp exposures. The occlusal surface of his dental enamel was generally abraded, and the dentin was heavily worn and uniformly shaded brown. The dental pulp chambers appeared originally to be within normal limits without any sign of obliteration, but over time (by age 4), the pulp chambers became partially or completely obliterated. The oldest affected member (age 59) showed mild hearing loss at high-frequency (8 kHz). Permanent dentition was severely affected in the adults, who had advanced dental attrition, premature loss of teeth, and extensive dental reconstruction.

Adolescent↗
PubMed2004

Relationship between circulating cytokine levels and thyroid function following bone marrow transplantation.

The relation between thyroid hormone changes and cytokines in bone marrow transplantation (BMT) patients has not been studied. This prospective study was designed to determine the relation between thyroid hormones and cytokine levels after BMT and their effects on the mortality. We studied 80 patients undergoing allogeneic BMT. Serum thyroid hormone parameters and cytokine levels were measured before and serially during 6 months after BMT. Serum T(3) decreased to a nadir 3 weeks post-BMT and serum T(4) was lowest at 3 months post-BMT. Serum thyroid stimulating hormone (TSH) sharply decreased to a nadir at 1 week and recovered. Serum interleukin-6 increased for 2 weeks after BMT and declined thereafter. Serum tumor necrosis factor-alpha increased for 3 weeks after BMT and declined thereafter. After 3 weeks post-BMT, both cytokine levels were negatively correlated with serum T(3) and T(4) levels. A total of 29 patients died before 1 year post-BMT and 51 patients survived longer than 1 year. Those patients who died before 1 year post-BMT had significantly lower levels of T(4) at 3 weeks, 3 and 6 months than surviving patients. In conclusion, increased levels of serum IL-6 and TNF-alpha were negatively correlated with thyroid hormone concentrations in BMT recipients suggesting the role of these cytokines in euthyroid sick syndrome.

Adult↗
PubMed2004

High-throughput method for detecting genomic-deletion polymorphisms.

DNA microarrays have been successfully used with different microorganisms, including Mycobacterium tuberculosis, to detect genomic deletions relative to a reference strain. However, the cost and complexity of the microarray system are obstacles to its widespread use in large-scale studies. In order to evaluate the extent and role of large sequence polymorphisms (LSPs) or insertion-deletion events in bacterial populations, we developed a technique, termed deligotyping, which hybridizes multiplex-PCR products to membrane-bound, highly specific oligonucleotide probes. The approach has the benefits of being low cost and capable of simultaneously interrogating more than 40 bacterial strains for the presence of 43 genomic regions. The deletions represented on the membrane were selected from previous comparative genomic studies and ongoing microarray experiments. Highly specific probes for these deletions were designed and attached to a membrane for hybridization with strain-derived targets. The targets were generated by multiplex PCR, allowing simultaneous amplifications of 43 different genomic loci in a single reaction. To validate our approach, 100 strains that had been analyzed with a high-density microarray were analyzed. The membrane accurately detected the deletions identified by the microarray approach, with a sensitivity of 99.9% and a specificity of 98.0%. The deligotyping technique allows the rapid and reliable screening of large numbers of M. tuberculosis isolates for LSPs. This technique can be used to provide insights into the epidemiology, genomic evolution, and population structure of M. tuberculosis and can be adapted for the study of other organisms.

DNA Probes↗
PubMed2003

Successful allogeneic hematopoietic stem cell transplantation using triple agent immunosuppression in severe aplastic anemia patients.

Graft rejection in patients with severe aplastic anemia (SAA) following allogeneic hematopoietic stem cell transplantation (HSCT) is strongly associated with a large number of prior transfusions and with prolonged disease duration before transplant. We retrospectively analyzed the outcomes and the factor affecting these multitransfused SAA patients, who had received triple agent immunosuppression and high doses of stem cells to overcome rejection. In total, 113 patients with SAA who had a median 16 months (range 1-216) of disease duration were transplanted using HLA-matched sibling donors after conditioning with cyclophosphamide (CY), procarbazine (PCB), and ATG. Graft failure occurred in 16 of the eligible 113 patients, and with a median follow-up of 30 months (range, 1-80), probability of overall rejection was 15%. Specifically, the multitransfused patients who received high doses of stem cells with T-cell depletion showed the lowest rejection rate, 5.6%, compared with 30.3% in multitransfused patients with bone marrow stem cells alone (P=0.0310). Disease duration (P=0.0338) and the number of infused CD34+cells (P=0.0101) were associated with a high risk of graft rejection on multivariate analysis. ABO mismatch and the number of CD34+ cells were significant factors in the incidence of acute graft-versus-host-disease (GVHD). The incidence of chronic GVHD among patients with sustained engraftment was 13/109 (11.9%). With the same follow-up period, probability of disease-free survival for the entire group of patients at 6 years was 89% and the only factor associated with long-term survival was rejection (P=0.0241). These results suggest that allogeneic HSCT conditioned with triple agent immunosuppression, and specifically with high-dose stem cell return is probably an effective treatment for successful engraftment in SAA patients with a high risk of rejection.

ABO Blood-Group System↗
PubMed2003

Diffusion-weighted MRI and ADC mapping in FK506 neurotoxicity.

FK506 is a newly developed potent immunosuppressant for preventing rejection after organ transplantation. However, FK506 can induce central nervous system toxicity. Until now the pathogenic mechanism of FK506 neurotoxicity was unclear. We report the findings of diffusion-weighted MRI and apparent diffusion coefficient (ADC) mapping of a FK506 neurotoxicity patient who showed increased signal intensities in both parieto-occipital lobes on T(2) weighted images, diffusion-weighted images and ADC maps. These findings suggest that a vasogenic oedema rather than a cytotoxic oedema may play a pivotal role in FK506 neurotoxicity pathogenesis.

Adult↗
PubMed2002

The role of cytokines in the changes in bone turnover following bone marrow transplantation.

Osteoporosis is a common disease among patients undergoing transplantation and a loss of bone mass is usually detected after bone marrow transplantation (BMT), particularly during the immediate post-BMT period. Post-BMT bone loss is primarily related to gonadal dysfunction and immunosuppression. Cytokines, especially interleukin 6, play an important role in the pathogenesis of postmenopausal osteoporosis. However, the pathogenetic role of cytokines in post-BMT bone loss is unknown and data on the changes of cytokines in accordance with bone turnover markers are scarce. The aim of this study was to assess the relationship between bone turnover markers and cytokines, which are regularly sampled at peripheral blood and bone marrow before and after allogeneic BMT. This prospective study included two analyses. The first was a study of 46 BMT recipients (M/F 28/18), examining the relationship between bone turnover markers and serum cytokines that were measured before and at 1 week, 2 weeks, 3 weeks, 4 weeks and 3 months after BMT. Serum intact parathyroid hormone was measured before BMT and at 3 weeks after BMT and its relation to other cytokines and bone turnover markers was evaluated. The second analysis was a study of 14 (M/F 9/5) of 46 patients in whom bone marrow plasma cytokines [interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)] were measured at 3 weeks after BMT. The relationship between bone marrow plasma cytokines and bone turnover markers was studied because bone marrow is the microenvironment where the real changes in bone turnover occur. Serum type I collagen carboxyterminal telopeptide (ICTP), a bone resorption marker, increased progressively until 4 weeks (peak) after BMT and then decreased thereafter. Serum osteocalcin, a bone formation marker, decreased progressively until 3 weeks after BMT and then increased thereafter. Serum IL-6 increased until 2 weeks after BMT and declined thereafter. Serum TNF-alpha increased until 3 weeks after BMT and declined thereafter. There was a significant positive correlation between serum ICTP and bone marrow IL-6 levels at 3 weeks after BMT, when a marked change in bone metabolism occurs following BMT. However, a correlation between bone turnover markers and bone marrow TNF-alpha or peripheral blood cytokines was not found. At 3 months after BMT, there was a significant negative correlation between the mean daily steroid dose and the serum osteocalcin level (r = -0.43, p < 0.05). The correlation between the Mean daily steroid dose and serum ICTP was also significant (r = 0.41, p < 0.05). Our data suggest that the progressive increase in bone resorption during the immediate post-BMT period is related to both steroid dose and the increase in bone marrow IL-6, which is a potent stimulator of bone resorption in vivo.

Adult↗
PubMed2001

Expression of leukemia-associated antigen, JL1, in bone marrow and thymus.

The identification of immunophenotypic markers with restricted expression has long been a critical issue in diagnostic and therapeutic advances for acute leukemias. We previously developed a monoclonal antibody against a new thymocyte surface antigen, JL1, and showed that JL1 is expressed in the majority of acute leukemia cases. In this study, using multiparameter flow cytometric analyses, we found that JL1 was uniquely expressed in subpopulations of normal bone marrow (BM) cells, implying the association of JL1 with the differentiation and maturation process. Although CD34(+) CD10(+) lymphoid precursors and some of maturing myeloid cells express JL1, neither CD34(+) CD38(-/lo) nor CD34(+) AC133(+) noncommitted pluripotent stem cells do. As for the myeloid precursors, CD34(+) CD33(+) cells do not express JL1. During lymphopoiesis, JL1 on the earliest lymphoid precursors disappear in the CD20(+) sIgM(+) stage of B-cell development or after CD1a down-regulation in thymocytes. Despite the highly restricted expression of JL1 in normal BM cells, most of the leukemias express JL1 irrespective of their immunophenotypes. These results indicate that JL1 is not only a novel differentiation antigen of hematopoietic cells, but also a leukemia-associated antigen. Therefore, we suggest that JL1 be a candidate molecule in acute leukemia for the diagnosis and immunotherapy that spares the normal BM stem cells.

Adult↗
PubMed2001

Allogeneic bone marrow transplantation for chronic myeloid leukemia: a retrospective study of busulfan-cytoxan versus total body irradiation-cytoxan as preparative regimen in Koreans.

From January 1990 to December 1997, 53 Korean patients with chronic myeloid leukemia (CML) receiving bone marrow transplantation (BMT) from human leucocyte antigen (HLA)-identical sibling donors conditioned with either busulfan and cyclophosphamide (BU/CY regimen) or total body irradiation and cyclophosphamide (TBI/CY regimen) were compared retrospectively. Transplantation-related mortality was 19% in BU/CY and 12% in TBI/CY, and early death (<100 d) occurred in 3 patients conditioned with BU/CY. Grade II-IV acute graft-versus-host disease (GVHD) was 9% of BU/CY and 52% of TBI/CY patients. Overall incidence of chronic GVHD was 50% of BU/CY and 52% of TBI/CY patients. In patients with chronic phase, 5-yr overall survival was 73% in the BU/CY group compared with 87% in the TBI/CY group (p=NS), and overall disease-free survival was 75% in the BU/CY group and 59% in the TBI/CY group (p=NS). So far, with a median follow-up of 45 months, 11 patients have relapsed; three relapses occurred after BU/CY and 8 after TBI/CY. The actuarial 5-yr relapse rate was 15% after BU/CY, 34% after TBI/CY (p=0.46). For patients transplanted in chronic phase within 1 yr after diagnosis, there was a clear trend for a lower relapse rate in the BU/CY group (5-yr relapse rate 0%) compared with the TBI/CY group (5-yr relapse rate 30%). The BU/CY group had similar BMT-related toxicity and similar overall survival and showed a clear trend of low relapse compared with the TBI/CY group. Therefore, BU/CY is an acceptable alternative for patients with CML during HLA-identical sibling allogeneic BMT.

Adult↗
PubMed2001

Effect of induced GVHD in leukemia patients relapsing after allogeneic bone marrow transplantation: single-center experience of 33 adult patients.

In a retrospective single center study, we examined the outcome of induced GVHD in leukemia patients relapsing after allogeneic BMT. Thirty-three adult patients with leukemia (15 AML, 3 ALL, and 15 CML) persisting or relapsing 1-36 months (median, 6) after allogeneic BMT underwent various immune manipulations and consequently developed acute and/or chronic GVHD at our center. Immunotherapies to elicit GVHD comprised chemotherapy followed by PBSC (n = 18), non-myeloablative transplant (n = 2), PBL followed by IFN-alpha (n = 5), PBL alone (n = 3), abrupt cessation of CsA (n = 3), and CsA withdrawal combined with IFN-alpha (n = 2). Twenty-four (72.7%) patients obtained a remission including complete hematological or cytogenetic remission, respectively, for acute leukemias or CML. Overall survival of patients, estimated at 3 years using the Kaplan-Meier method, was 33.9% (95% CI, 20-52%). Twelve patients including two patients with ALL remain in complete hematological (n = 5) or cytogenetic remission (n = 7) 3-93 months (median 12) after achieving remission. Twelve (63.2%) of 19 dead patients died due to treatment-related toxicities; five patients from acute GVHD, three from GVHD followed by infections and four from infections. By multivariate Cox analysis, only chronic GVHD resulted in a higher probability of disease-free survival (P = 0.026). Eight patients who had both acute GVHD < or = grade I and chronic GVHD are all alive without leukemia. We conclude that acute GVHD is associated with considerable toxicity while chronic GVHD plays a role in retaining remission in leukemia relapsing after allogeneic BMT.

Adolescent↗
PubMed2001

Changes in autoimmune thyroid disease following allogeneic bone marrow transplantation.

Autoimmune diseases can be transmitted and eliminated by bone marrow transplantation (BMT). There have been several cases of autoimmune thyroid disease (AITD) occurring after BMT, but AITD remission has been rarely reported. We present four cases in which the remission or transfer of AITD occurred after an allogeneic BMT. Two patients with severe aplastic anemia (SAA) showed evidence of remission of Hashimoto's thyroiditis which they had before allogeneic BMT. One patient with SAA, which developed during treatment with propylthiouracil for Graves' disease, underwent allogeneic BMT and showed evidence of Graves' disease remission following BMT. In one patient, new AITD occurred after an allogeneic BMT from an HLA-matched sibling who already had AITD. These cases support the evidence that the immune system is newly reconstituted after BMT, and severe autoimmune disease can be an indication for BMT. To fully understand the real changes in autoimmune status after BMT, long-term prospective studies are necessary.

Adolescent↗
PubMed2001

The kinetics of circulating cytokines including IL-6, TNF-alpha, IL-8 and IL-10 following allogeneic hematopoietic stem cell transplantation.

Pro-inflammatory (IL-6, TNFalpha and IL-8) and anti-inflammatory (IL-10) cytokines were determined in weekly samples from 52 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IL-6 increased immediately after transplant peaking at week +3, but IL-8 concentrations were elevated only during week +1. After a slight decrease in week +1, TNF-alpha significantly increased from week +2 and peaked at week +3, whereas, IL-10 values started to rise in week +2 and peaked during week +4. IL-6 and TNF-alpha were positively correlated from week +2 to week +4, and IL-6 levels at week +1 were related with fever and severe stomatitis. Serum levels of IL-6 at week +1 and IL-10 at week +4 were significantly higher in patients with early transplant-related complications, such as fever, severe stomatitis or acute GVHD > or = overall grade II than in those without the complications. We conclude that a high serum IL-6 level at week +1 may be an early predictor of transplant-related complications and that it seems to trigger pro- and anti-inflammatory cytokine release. Kinetic patterns of IL-6 and IL-10 were more exaggerated in those with complications after HSCT.

Acute Disease↗
PubMed2001

Conditioning with high-dose cyclophosphamide may not be sufficient to provide a long-term remission of paroxysmal nocturnal hemoglobinuria following syngeneic peripheral blood stem cell transplantation.

A patient with paroxysmal nocturnal hemoglobinuria (PNH) received a syngeneic peripheral blood stem cell transplant (PBSCT) with high-dose cyclophosphamide (CY) conditioning. He had a reasonable engraftment and complete hematologic recovery. However, at 12 months after PBSCT, he became symptomatic and peripheral blood cells were almost entirely composed of glycosylphosphatidylinositol-anchored proteins deficient cells. This case suggests that high-dose CY may not exert a significant effect on PNH clones in the long term, although it had been effective in allogeneic BMT. In view of the possible autoimmune basis, it seems to be necessary to include other immunosuppressive therapy including ALG in addition to CY.

Adult↗