PubMed Health⌕ Search

Biomedical subjects

K-H Lee

Publications and source records attributed to K-H Lee.

At least 19 recordsLinked to original sources
PubMed2007

RNA polymerase beta-subunit gene (rpoB) sequence analysis for the identification of Bacteroides spp.

Partial rpoB sequences (317 bp) of 11 species of Bacteroides, two Porphyromonas spp. and two Prevotella spp. were compared to delineate the genetic relationships among Bacteroides and closely related anaerobic species. The high level of inter-species sequence dissimilarities (7.6-20.8%) allowed the various Bacteroides spp. to be distinguished. The position of the Bacteroides distasonis and Bacteriodes merdae cluster in the rpoB tree was different from the position in the 16S rRNA gene tree. Based on rpoB sequence similarity and clustering in the rpoB tree, it was possible to correctly re-identify 80 clinical isolates of Bacteroides. In addition to two subgroups, cfiA-negative (division I) and cfiA-positive (division II), of Bacteroides fragilis isolates, two distinct subgroups were also found among Bacteroides ovatus and Bacteroides thetaiotaomicron isolates. Bacteroides genus-specific rpoB PCR and B. fragilis species-specific rpoB PCR allowed Bacteroides spp. to be differentiated from Porphyromonas and Prevotella spp., and also allowed B. fragilis to be differentiated from other non-fragilisBacteroides spp. included in the present study.

Bacterial Proteins↗
PubMed2006

Aerosol delivery of Akt controls protein translation in the lungs of dual luciferase reporter mice.

Lung cancer has emerged as a leading cause of cancer death in the world; however, most of the current conventional therapies are not sufficiently effective in altering the progression of disease. Therefore, development of novel treatment approaches is needed. Although several genes and methods have been used for cancer gene therapy, a number of problems such as specificity, efficacy and toxicity reduce their application. This has led to re-emergence of aerosol gene delivery as a noninvasive method for lung cancer treatment. In this study, nano-sized glucosylated polyethyleneimine (GPEI) was used as a gene delivery carrier to investigate the effects of Akt wild type (WT) and kinase deficient (KD) on Akt-related signaling pathways and protein translation in the lungs of CMV- LucR-cMyc-IRES-LucF dual reporter mice. These mice are a powerful tool for the discrimination between cap-dependent/-independent protein translation. Aerosols containing self-assembled nano-sized GPEI/Akt WT or GPEI/Akt KD were delivered into the lungs of reporter mice through nose-only-inhalation-chamber with the aid of nebulizer. Aerosol delivery of Akt WT caused the increase of protein expression levels of Akt-related signals, whereas aerosol delivery of Akt KD did not. Furthermore, dual luciferase activity assay showed that aerosol delivery of Akt WT enhanced cap-dependent protein translation, whereas a reduction in cap-dependent protein translation by Akt KD was observed. Our results clearly showed that targeting Akt may be a good strategy for prevention as well as treatment of lung cancer. These studies suggest that our aerosol delivery is compatible for in vivo gene delivery which could be used as a noninvasive gene therapy in the future.

Aerosols↗
PubMed2006

Merlin facilitates ubiquitination and degradation of transactivation-responsive RNA-binding protein.

The Nf2 tumor suppressor codes for merlin, a protein whose function is largely unknown. We have previously demonstrated a novel interaction between merlin and TRBP, which inhibits the oncogenic activity of TRBP. In spite of the significance of their functional interaction, its molecular mechanism still remains to be elucidated. In this report, we investigated how merlin inhibits the oncogenic activity of TRBP in association with cell growth conditions. In the human embryonic kidney 293 cell line, the level of endogenous merlin increased, whereas that of endogenous TRBP significantly decreased along with the increase in cell confluence. We demonstrated that the carboxyl-terminal region of TRBP was responsible for this phenomenon using stable cell lines expressing deletion mutants of TRBP. The overexpression of merlin decreased the protein level of TRBP, and the ubiquitin-like subdomain of merlin's FERM domain was important for this activity. We also demonstrated that TRBP is ubiquitinylated and the ubiquitinylated forms of TRBP are accumulated by ectopically expressed merlin or cell confluence in the presence of MG132, a proteasome inhibitor. Furthermore, we showed that the regulation of TRBP in response to cell confluence was abolished upon knockdown of merlin expression by specific small interfering RNA. Finally, we showed that ectopically expressed merlin restored cell-cell contact inhibition in cells stably expressing TRBP but not in TRBPDeltac. These results suggest that merlin is involved in the regulation of TRBP protein level by facilitating its ubiquitination in response to such cues as cell-cell contacts.

Animals↗
PubMed2006

Risk-factor analysis for predicting progressive- or quiescent-type chronic graft-versus-host disease in a patient cohort with a history of acute graft-versus-host disease after allogeneic stem cell transplantation.

This study attempts to identify variables that can predict the development of progressive- or quiescent-type chronic GVHD (pq cGVHD) and transplant outcomes after the diagnosis of cGVHD in 99 patients who experienced acute GVHD (aGVHD) after allogeneic SCT. The prognostic significance of various clinical parameters at diagnosis of cGVHD was examined to determine the prognostic factors for GVHD-specific survival (GSS) in patients with pq cGVHD. Among 118 patients who experienced any degree of aGVHD, 99 were evaluated for cGVHD. The incidence of overall and extensive pq cGVHD at 2 years was estimated as 84.4 and 63.1%, respectively. A multivariate analysis showed that severe aGVHD (grade 3, 4) (P=0.022), primary treatment failure (P=0.009) and elevated alkaline phosphatase (P=0.001) were all significant independent factors predicting a higher overall incidence of pq cGVHD. The GSS and probability of systemic immunosuppressive treatment at 2 years after diagnosis of cGVHD were estimated as 55.9 and 51.9%. GVHD-specific survival was significantly associated with performance status (P=0.004) and lymphocytopenia (<or=1000/microl, P=0.022) at diagnosis of cGVHD by Cox's proportional hazard model. Severe aGVHD, primary treatment failure (PTF), lymphocytopenia and elevated alkaline phosphatase may be useful predictive factors for the development of pq cGVHD in patients who experience aGVHD after allogeneic SCT.

Acute Disease↗
PubMed2006

Risk score model for fatal intracranial hemorrhage in acute leukemia.

To build a risk score (RS) model of fatal intracranial hemorrhage (FICH) in patients with acute leukemia, we retrospectively assessed risk factors in 792 patients newly diagnosed with acute leukemia, 41 of whom had analyzable FICH. We found that female gender (relative risk (RR) = 5.234, P<0.001), acute promyelocytic leukemia (RR = 4.057, P = 0.003), leukocytosis (RR = 3.301, P = 0.004), thrombocytopenia (RR = 3.283, P = 0.005) and prolonged prothrombin time (RR = 3.291, P = 0.016) were significantly associated with occurrence of FICH in multivariate analysis. To calculate RS for FICH, one point was assigned for each risk factor, making the RS between 0 and 5. The RS model segregated patients into three prognostic groups: a low-risk group (LRG) for RS of 0 or 1; an intermediate-risk group (IRG) for RS of 2 or 3; and a high-risk group (HRG) for RS of 4 or 5. Expectation of FICH was well correlated with risk groups (all P-values < 0.001). Overall survival was significantly shorter in the HRG compared with the LRG. The RS model we constructed to predict the occurrence of FICH will be verified through prospective studies.

Acute Disease↗
PubMed2006

Headaches and the N95 face-mask amongst healthcare providers.

BACKGROUND: During the 2003 severe acute respiratory distress syndrome epidemic, healthcare workers mandatorily wore the protective N95 face-mask. METHODS: We administered a survey to healthcare workers to determine risk factors associated with development of headaches (frequency, headache subtypes and duration of face-mask wear) and the impact of headaches (sick days, headache frequency and use of abortive/preventive headache medications). RESULTS: In the survey, 212 (47 male, 165 female) healthcare workers of mean age 31 years (range, 21-58) participated. Of the 79 (37.3%) respondents who reported face-mask-associated headaches, 26 (32.9%) reported headache frequency exceeding six times per month. Six (7.6%) had taken sick leave from March 2003 to June 2004 (mean 2 days; range 1-4 days) and 47 (59.5%) required use of abortive analgesics because of headache. Four (2.1%) took preventive medications for headaches during this period. Multivariate logistic regression showed that pre-existing headaches [P = 0.041, OR = 1.97 (95% CI 1.03-3.77)] and continuous use of the N95 face-mask exceeding 4 h [P = 0.053, OR = 1.85 (95% CI 0.99-3.43)] were associated with development of headaches. CONCLUSIONS: Healthcare providers may develop headaches following the use of the N95 face-mask. Shorter duration of face-mask wear may reduce the frequency and severity of these headaches.

Adult↗
PubMed2005

Interaction of beta-giardin with the Bop1 protein in Giardia lamblia.

A cDNA clone encoding a putative Bop1 homologous protein was identified in Giardia lamblia. Since Bop1 is a nucleolar protein involved in rRNA processing, thereby controlling the cell cycle, we investigated components of cell cycle control in G. lamblia by identifying the protein(s) that interact with Bop 1. Through an immunoaffinity column made with polyclonal antibodies specific to the recombinant Bop1 of G. lamblia, a pool of proteins was obtained from the crude extracts of Giardia and then used as antigens to immunize rats. By employing the resultant sera for cDNA library immunoscreening, we isolated cDNA clones encoding an immunopurified protein, which turned out to contain the gene for beta-giardin, a Giardia-specific cytoskeletal protein. The interaction between Bop1 and beta-giardin was confirmed via two different methods, yeast two-hybrid assay and coimmunoprecipitation.

Amino Acid Sequence↗
PubMed2005

Bilirubin appears to be the only independent variable affecting mortality on liver transplant waiting list if waiting time exceeds 1 year.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score has been shown to be the best predictor of short-term mortality on the liver transplant waiting list in the United States but waiting time often exceeds 1 year in many countries. We wanted to identify the factors affecting mortality on the liver transplant waiting list in Singapore where waiting time for liver transplant exceeds 1 year. PATIENTS AND METHODS: All patients who were listed on the liver transplant waiting list in Singapore from January 1997 to December 2003 excluding those who were transplanted were analyzed. MELD was calculated according to the United Network for Organ Sharing formula. Univariate analysis was performed to identify factors affecting mortality on the waiting list and multivariate analysis by logistic regression. Categorical and continuous variables were compared with the chi-square and Mann-Whitney U tests. RESULTS: There were 48 patients in the study. We found that on univariate analysis, bilirubin, INR, MELD score, and Child's score significantly influenced mortality on the waiting list but on multivariate analysis, bilirubin was the only independent prognostic indicator of mortality on the waiting list (LR = 1.97; 95% confidence interval = 1.08 to 3.61). INR was found to be significantly correlated to bilirubin with Pearson correlation (R = 0.63, P < .001). CONCLUSION: Bilirubin is the only independent factor affecting mortality on the liver transplant waiting list where waiting time exceeds 1 year.

Analysis of Variance↗
PubMed2005

Severe metabolic abnormalities after allogeneic hematopoietic cell transplantation.

Severe metabolic abnormalities occurring within 100 days after allogeneic hematopoietic cell transplantation (HCT) were investigated in 311 patients. The metabolic abnormalities included hyper- and hypocalcemia, hypophosphatemia, hyper- and hypokalemia, hyper- and hyponatremia, hyper- and hypomagnesemia, hypercholesterolemia, hyper- and hypoglycemia, and hyperuricemia. Severe abnormalities, defined as grades III-V by NCI CTCAE v3.0, occurred in 269 patients (86.5%). Multivariate analysis revealed that patients with moderate-to-severe hepatic veno-occlusive disease had significantly higher risk for the occurrence of severe metabolic abnormalities. Grades III-IV acute graft-versus-host disease was the most frequently associated with individual metabolic abnormalities. Patients with at least one severe metabolic abnormality had significantly higher day 100 nonrelapse mortality (P=0.015) and lower 5-year overall survival (P=0.002) than those without severe abnormalities. The number of metabolic abnormalities also stratified the patients with different clinical outcomes. In conclusion, severe metabolic abnormalities occurring within 100 days after allogeneic HCT were common, and their occurrence was significantly associated with inferior clinical outcomes. These results indicate that metabolic parameters should be monitored in patients undergoing allogeneic HCT and that the occurrence of severe metabolic abnormalities should be considered an important toxicity parameter in prospective clinical trials regarding allogeneic HCT.

Adolescent↗
PubMed2005

Non-total body irradiation containing preparative regimen in alternative donor bone marrow transplantation for severe aplastic anemia.

Using non-total body irradiation (TBI) containing preparative regimens, 13 patients with severe aplastic anemia (SAA) were transplanted from an alternative donor in a single institute. In total, 12 donors were unrelated volunteers and one was an HLA one-locus mismatched sibling. Median time from diagnosis of SAA to bone marrow transplantation (BMT) was 10.1 months (range, 1.6-180.1). Nine patients had received immunosuppressive treatment with ATG before BMT, while four had not. Preparative regimens consisted of cyclophosphamide plus ATG in nine patients, cyclophosphamide plus fludarabine in two patients, and cyclophosphamide plus fludarabine plus ATG in two patients. All patients received non-T-cell depleted bone marrow from the donor. Cyclosporine plus methotrexate were given for GVHD prophylaxis. All patients engrafted on a median of day 21 (range, 15-27). Grade III-IV acute GVHD developed in three (23%) of 13 patients and extensive chronic GVHD in four (31%) of 12 evaluable patients. With a median follow-up duration of 1138 days (range, 118-1553), 10 patients are alive with durable engraftment showing 74.6% (95% confidence interval, 49.5-99.7%) of survival rate. Cause of the deaths was CNS bleeding in one and chronic GVHD in two. In conclusion, non-TBI containing preparative regimen could ensure durable engraftment in alternative donor BMT for SAA and showed promising results.

Adolescent↗
PubMed2005

Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a prospective study.

Donor leukocyte infusion (DLI) alone has very limited efficacy for patients with acute lymphoblastic leukemia (ALL) who have relapsed after allogeneic bone marrow transplantation (BMT). We, therefore, prospectively tested the efficacy of cytoreductive chemotherapy (intermediate-dose cytarabine+idarubicin+etoposide) followed immediately by G-CSF-primed DLI (Chemo-DLI) in 10 relapsed ALL patients after allogeneic BMT. Seven achieved complete remission (CR) at a median of 25 days (19-73 days) after DLI. Of these seven CR patients, only one remains alive in CR 907 days after DLI. Two CR patients died in CR of graft-versus-host disease. The remaining four CR patients relapsed at a median of 153 days (120-991 days) after DLI. One is alive with leukemia at post-DLI day 1217. The median survival duration after DLI was 175 days (15-1217 days). In summary, although Chemo-DLI for relapsed ALL after allogeneic BMT induced a relatively high CR rate, durable remissions were rare. Although our data should be interpreted cautiously considering the small number of patients, these results suggest that poor outcome of DLI in relapsed ALL may be primarily due to intrinsic resistance to graft-versus-leukemia effect rather than to the rapid pace of the disease.

Adult↗
PubMed2005

Clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.

Clinical impact of imatinib was evaluated in 20 patients (median age, 37 years; range, 15-67 years) with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), who were administered with induction chemotherapy of daunorubicin, vincristine, prednisolone, and L-asparaginase, along with imatinib 600 mg/day during remission induction and 400 mg/day during consolidation courses. One patient died on day 14 from septic shock, while the remaining 19 achieved complete remission (CR). In total, 15 patients underwent allogeneic hematopoietic cell transplantation (HCT) during first CR. After median follow-up period of 799 days, six patients experienced recurrence; two with early recurrence within 100 days, one with leptomeningeal recurrence at 11 month, and three with post-HCT recurrence. Eight patients died. Median CR duration (821 days) and median patient survival (894 days) in the study were significantly longer by 2.9- and 2.3-fold, respectively, when compared to those of 18 historical patients treated with same regimen of combination chemotherapy without imatinib. Toxicities of the combined treatment were manageable and included grade 4 myelosuppression (n = 20) and reversible > or = grade 3 hyperbilirubinemia (n = 4). Beneficial clinical effects were observed when imatinib was added to combination chemotherapy in patients with newly diagnosed Ph+ ALL. Further studies with larger number of patients are necessary.

Adolescent↗
PubMed2005

A case of chromoblastomycosis with an unusual clinical manifestation caused by Phialophora verrucosa on an unexposed area: treatment with a combination of amphotericin B and 5-flucytosine.

Chromoblastomycosis is a cutaneous and subcutaneous mycotic disease caused by the dematiaceous (black) fungi. Five species of fungi are known generally to be the cause: Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii, F. compacta and Rhinocladiella cerphilum. In infected tissue they can appear as pigmented sclerotic bodies, commonly called 'copper pennies', which are pathognomonic of chromoblastomycosis. The infection usually occurs through traumatic skin inoculation, with the majority of lesions occurring on the feet and legs of outdoor workers. We report a patient in whom the lesions had begun on the right breast, which is an unexposed area, without a history of trauma. A uniform, reliable treatment does not exist but our patient was mycologically cured with the use of amphotericin B and the subsequent combination of 5-flucytosine and itraconazole.

Adult↗
PubMed2004

Adefovir dipivoxil as the rescue therapy for lamivudine-resistant hepatitis B post liver transplant.

INTRODUCTION: Complications of hepatitis B virus (HBV) infection are among the most common indications for liver transplant in many parts of Asia. However, none of the current posttransplant hepatitis B prophylaxis strategies, namely, lamivudine, hepatitis B immunoglobulin monotherapy, or combination therapy, is ideal. Our aim was to evaluate the use of adefovir dipivoxil (ADV) as a rescue therapy for posttransplant HBV patients who developed lamivudine resistance. METHODS: Twenty-two consecutive patients with HBV-related liver disease, who underwent first liver transplants from 1995 to 2002, received HBV prophylaxis with indefinite lamivudine with substitution of ADV for patients who developed drug resistance and clinical deterioration, defined as persistent elevation of transaminases or histologic deterioration. RESULTS: Sixteen patients (73%) were alive at their last follow-up and six (38%) had developed hepatitis B recurrence at a median of 46 (range 9 to 74) months posttransplant. Two with persistently normal transaminases and normal liver histology at 3 and 42 months postrecurrence have been continued on lamivudine. Four showed clinical deterioration and received ADV for a median of 24 months; all displayed normalization of transaminases and a 2 to 5 log drop in HBV DNA titers. Three had paired biopsies before and after substitution of ADV with two showing improvement and one stable appearance. The median serum creatinine value increased slightly from 126 to 138 micromol/L (P = 0.72). CONCLUSION: ADV is an effective rescue therapy for patients with lamivudine-resistant hepatitis B post-liver transplant. Further studies are needed to ascertain the optimal posttransplant hepatitis B prophylaxis.

Adenine↗
PubMed2004

Renal impairment and diabetes mellitus after liver transplant.

INTRODUCTION: One of the major concerns in liver transplant patients who survive past 1 year posttransplant is the development of chronic diseases. AIM: We studied two important clinical conditions that can have a chronic course-renal impairment and diabetes mellitus-among long-term liver transplant survivors. METHODS: All adult patients transplanted and followed for at least 1 year were evaluated for clinical status, blood tests, and imaging studies. The occurrence and development of renal impairment, defined as a serum creatinine above 125 micromol/L or creatinine clearance less than 75 mL/min, or diabetes mellitus were evaluated for contributing factors. RESULTS: The 35 evaluated patients of mean age at transplant of 50 years had a mean follow-up duration of 45 months. The incidence of posttransplant renal impairment was 22.8% at 1 year and 47.6% at 3 years. This disorder was associated with pretransplant renal impairment and with a diagnosis of diabetes. Posttransplant diabetes mellitus was observed in 48.6% with 41.1% resolving over time. CONCLUSION: Posttransplant renal impairment appears to be a potential long-term problem. Although this relates to pretransplant conditions, longer follow-up is required to examine whether posttransplant factors contribute to its progression.

Adolescent↗
PubMed2004

Persistent thrombocytopenia in liver transplant patients.

INTRODUCTION: The occurrence of thrombocytopenia in the perioperative period after a liver transplant is not uncommon. However, there are few studies on persistent thrombocytopenia during the longer follow up period of patients after liver transplantation. We examined the prevalence of and contributing factors to persistent thrombocytopenia beyond 1 year post-liver transplantation. METHODS: We analyzed adult patients followed for at least 1 year posttransplant with full blood counts and abdominal scans, as well as clinical notes. RESULTS: The 35 patients of mean age at transplant of 50 years and showed a mean follow-up of about 4 years showed a prevalence of persistent thrombocytopenia at 12 months of 54% and at 3 years of 25%. Factors that were associated with persistent thrombocytopenia were pretransplant variceal bleeding, splenomegaly, and thrombocytopenia at 3 and 6 months posttransplant. After multivariate analysis only the latter represented independent factors for persistent thrombocytopenia at 1 and 3 years posttransplant, respectively. CONCLUSION: Persistent thrombocytopenia improved over time posttransplant; no bleeding problem was observed among the affected cases.

Adolescent↗