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Biomedical subjects

C K Lee

Publications and source records attributed to C K Lee.

At least 55 records · Page 3Linked to original sources

A comparison of the supra-alveolar pulp size of impeded and unimpeded mandibular rat incisors using micro-computed tomography.

The pulp space is almost totally obliterated in the incisal end of a mandibular rat incisor. Repeated shortening of the incisor has been shown to increase the pulp space below the alveolar bone level; however, little is known about that above the alveolar bone level. This study investigated the changes in the pulp space superior to the bone level after rendering the incisor unimpeded for a period of three weeks. A desktop micro-computed tomography scanning unit, which is non-invasive, non-destructive, accurate, less technique sensitive and less time consuming than conventional methods, was used to calculate the volume of the pulp space. The results showed that the pulp size increased 140% at a level 3 mm below the alveolar bone margin and more than 700% at a level 2.5 mm above the alveolar bone. Moreover, the bone level of the unimpeded incisor was found to move incisally 0.4-0.5 mm; while deposition of dentine on the mesial and distal aspects of the pulp space were affected differently to that on the buccal and lingual sides.

Animals↗

Two halodeoxy sucrose analogues.

At 160 K, the structure of 4-bromo-4-deoxysucrose, C(12)H(21)BrO(10), is very similar to that of sucrose, particularly with respect to the conformation of the glycosidic linkage. As in sucrose, an intramolecular hydrogen bond exists between the glucopyranosyl and the fructofuranosyl rings. Conversely, the structure of 1',6'-dibromo-4-fluoro-4,1',6'-trideoxysucrose monohydrate, C(12)H(19)Br(2)FO(8) x H(2)O, shows large conformational differences when compared with the structures of both sucrose and sucralose. This compound does not exhibit any intramolecular hydrogen bonds. In each compound, a complex series of intermolecular hydrogen bonds link the molecules into an infinite three-dimensional framework. The absolute configuration of each molecule has been determined.

Crystallography, X-Ray↗

Dynamic sagittal imbalance of the spine in degenerative flat back: significance of pelvic tilt in surgical treatment.

STUDY DESIGN: A retrospective study of 26 patients with degenerative flat back treated with corrective osteotomy. OBJECTIVE: To analyze dynamic sagittal imbalance and to elucidate the cause of postoperative persistent stooping in degenerative flat back. SUMMARY OF BACKGROUND DATA: Sagittal spinal imbalance in degenerative flat back was more evident on walking, suggesting its dynamic nature. The most puzzling complication in its surgical treatment was postoperative persistent stooping. METHODS: This study analyzed 26 surgically treated patients with preoperative gait analysis. Patients were divided into two groups according to postoperative improvement in stooping: Group 1 with marked improvement in stooping and Group 2 with persistent stooping. Various radiographic and gait parameters were compared between the two groups. RESULTS: Comparison of radiographic parameters, representing the static status of the spine, did not indicate any clue to the mechanism for persistent stooping. However, comparison of gait parameters, representing the dynamic status of the spine, revealed meaningful differences between the two groups. Among various gait parameters compared, pelvic tilt seemed to be the most important clue. Patients in Group 1 showed posterior pelvic tilt, whereas those in Group 2 showed marked anterior pelvic tilt. CONCLUSION: Degenerative flat back could be classified into two types based on pelvic position during walking: one with posterior pelvic tilt and the other with marked anterior pelvic tilt. In the former type, corrective surgery improved the stooping. In the latter, corrective surgery was ineffective, resulting in postoperative persistent stooping.

Adult↗

Sterilizing immunity against experimental Helicobacter pylori infection is challenge-strain dependent.

The development of a murine model of Helicobacter pylori infection through serial in vivo passage of candidate strains has enabled a quantitative assessment of vaccine efficacy. In this study we compare infection with and protection against challenge from both CagA(+) type I, and CagA(-) type II in vivo adapted isolates. In vivo passage of a type II H. pylori isolate resulted in a highly infectious strain (X47-2AL), capable of reproducibly infecting mice to high density (10(7) CFU/g of gastric tissue). Similarly adapted type I strains were found to colonize mice at a significantly lower level (10(4)-10(5) CFU/g tissue). Mucosal immunization with recombinant urease (rUre) significantly protected animals against both types. Protection against X47-2AL was characterized by a > or =100-fold (or 2 log) reduction in bacterial density. However, the presence of a residual infection highlighted the inability to achieve sterilizing immunity against this strain. The level of protection appeared independent of challenge dose, and was stable for up to 6 months, all animals exhibiting a low-level residual infection that did not recrudesce with time. Similarly immunized mice challenged with isolates representing the residual infection were also protected, confirming that they did not represent a sub-population of H. pylori that could escape immunity. Immunization and challenge studies with type I adapted-isolates, demonstrated a similar 2-3 log reduction in the bacterial burden, but that in this instance resulted in sterilizing immunity. These results suggest varied specificity for the murine host by different Helicobacter strains that can influence the outcome of both infection and immunity.

Administration, Oral↗

3-O-acetyl-4-deoxy-4-iodo-beta-D-fructofuranosyl 2,3,6-tri-o-acetyl-4-chloro-4-deoxy-alpha-D-glucopyranoside.

At 160 K, the glucopyranosyl ring of the title compound, C(20)H(28)ClIO(13), has a near-ideal (4)C(1) conformation and the fructofuranosyl ring has a twist (4)T(3) conformation. The two hydroxy groups are involved in intra- and intermolecular hydrogen bonds, with the latter interactions linking the molecules into infinite one-dimensional chains. The absolute configuration of the molecule has been determined.

Carbohydrate Conformation↗

Macroscopic chirality of a liquid crystal from nonchiral molecules.

The transfer of chirality from nonchiral polymer networks to the racemic B2 phase of nonchiral banana-shaped molecules is demonstrated. This corresponds to the transfer of chirality from an achiral material to another achiral material. There are two levels of chirality transfers. (a) On a microscopic level the presence of a polymer network (chiral or nonchiral) favors a chiral state over a thermodynamically stable racemic state due to the inversion symmetry breaking at the polymer-liquid crystal interfaces. (b) A macroscopically chiral (enantimerically enriched) sample can be produced if the polymer network has a helical structure, and/or contains chemically chiral groups. The chirality transfer can be locally suppressed by exposing the liquid crystal to a strong electric field treatment.

Journal Article↗

Generation of macrophages from early T progenitors in vitro.

Early T progenitors in the thymus have been reported to have the capacity to develop into B cells, thymic dendritic cells, and NK cells. Here we describe conditions that induce early T progenitors to develop into macrophages. Initially, we observed that early T progenitors could be induced to develop into macrophages by cytokines produced from a thymic stromal cell line, TFGD, and later we found that the cytokine mixture of M-CSF plus IL-6 plus IL-7 also induced macrophage differentiation from pro-T cells. M-CSF by itself was unable to induce macrophage differentiation from early T progenitors. To correlate this observation with the developmental potential of early T progenitors, mouse embryonic thymocytes were sorted into four populations, pro-T1 to pro-T4, based on the expression of CD44 and CD25, and then cultured with TFGD culture supernatant. We found that pro-T1 and pro-T2 cells, but not pro-T3 and pro-T4 cells, generate macrophages. Limiting dilution analysis of the differentiation capability of sorted pro-T2 cells also confirmed that pro-T2 cells could generate macrophages. These results suggest that T cells and thymic macrophages could originate from a common intrathymic precursor.

Animals↗

Immunogenicity of the E1E2 proteins of hepatitis C virus expressed by recombinant adenoviruses.

The E1 and E2 proteins of hepatitis C virus (HCV) are believed to be the viral envelope glycoproteins that are major candidate antigens for HCV vaccine development. We reported previously that the replication-competent recombinant adenovirus encoding core-E1-E2 genes of HCV (Ad/HCV) produces serologically reactive E1 and E2 proteins forming a heterodimer in substantial amounts. Here, we examined immunogenicity of the E1E2 proteins copurified from HeLa cells infected with Ad/HCV virus in mice. Furthermore, we constructed a replication-defective recombinant adenovirus encoding the core-E1-E2 genes of HCV (Ad.CMV.HCV) and examined immunogenicity of the virus in mice. The mice immunized intraperitoneally with the copurified E1E2 proteins induced mainly antibodies to E2, but not to E1 by Western blot analysis. The sera of mice immunized with the E1E2 inhibited the binding of E2 protein to the major extracellular loop of human CD81. E2-specific cytotoxic T cells (CTLs), but not antibodies to the E1E2 antigens were induced in the mice intramuscularly immunized with Ad.CMV.HCV virus. When immunized with both Ad.CMV.HCV virus and the E1E2, mice elicited E2-specific CTLs and antibodies to the E1E2 antigens. The results suggest that immunization of Ad.CMV.HCV virus combined with E2 protein is an effective modality to induce humoral as well as cellular immune response to E2 antigen.

Adenoviridae↗

Syntheses and structure--activity relationships of novel apio and thioapio dideoxydidehydronucleosides as anti-HCMV agents.

On the basis of the fact that apio dideoxynucleosides, in which the furanose oxygen and the C2 of the 2,3-dideoxyribose are transposed, exhibited potent anti-HIV activity and 2',3'-dideoxy-2',3'-didehydronucleosides also showed potent anti-HIV activity, we synthesized apio dideoxydidehydronucleosides in which the oxygen atom and the double bond of the 2,3-dideoxy-2,3-didehydroribose are exchanged. The thioapio dideoxydidehydronucleosides were also synthesized since sulfur serves as a bioisostere of oxygen. Apio dideoxydidehydronucleosides 13a--f were synthesized starting from 1,3-dihydroxyacetone, utilizing phenylselenenyl chemistry as a key step. The ratio of the anomeric mixture was variable from 1:1 to 5:1 during the condensation of nucleosidic bases with the phenylselenyl acetate 11 in the presence of a Lewis acid. This is in contrast with other glycosyl donors such as 5-O-(tert-butyldiphenylsilyl)-2-phenylselenenyl-2,3-dideoxyribosyl acetate which shows excellent neighboring group effect (alpha:beta = 1:99). Thioapio dideoxydidehydronucleosides 22a,b were synthesized from the lactone 9 via thiolactone 17 as a key intermediate which was synthesized from dicyclohexylcarbodiimide coupling of the mercapto acid produced from the basic hydrolysis of thioacetate 16. The majority of apio analogues synthesized in this study exhibited moderate to potent anti-HCMV activity, among which the 5-fluorouracil derivative 13c was found to be the most potent against HCMV, while thioapio analogues showed no activity against HCMV. However, all synthesized compounds did not exhibit any significant activities against HIV-1, HSV-1, and HSV-2. The fact that apio dideoxydidehydronucleosides were active against HCMV suggests that the apio dideoxydidehydro sugar moiety can serve as a novel template for the development of new antiviral agents.

Antiviral Agents↗

Thymic emigrants isolated by a new method possess unique phenotypic and functional properties.

T cells that emigrate from the thymus have primarily been studied in vivo using fluorescent dye injection of the thymus. This study examined the properties of thymocytes that emigrate from cultured thymic lobes in organ culture. Under these conditions, thymic emigrants displayed the expected phenotype, that of mature thymocytes expressing high levels of T-cell receptor (TCR-alphabeta) and either CD4 or CD8, and were observed to emigrate within 24 hours of positive selection. Emigration was inhibited by cytochalasin D, pertussis toxin, or Clostridium difficile toxin B, implicating an active motility process. Most of the surface markers on alphabeta-thymic emigrants (Thy1, CD44, CD69, CD25, leukocyte functional antigen-1, intercellular adhesion molecule-1, alpha(4)-integrin, alpha(5)-integrin, CD45, and CD28) were expressed at a surface density similar to that on mature intrathymic cells and peripheral splenic T cells. Heterogeneous expression of L-selectin and heat-stable antigen (HSA) suggested that subsets emerge from the thymus with a commitment to different migration patterns. The only marker on emigrants not found on either intrathymic cells or mature spleen T cells was CTLA-4, which could dampen the response of emigrants to peripheral antigens. Antigen responsivenes measured in vitro against allogeneic dendritic cells showed a proliferative response comparable to that of splenic T cells. In vivo, however, thymic emigrants failed to induce an acute graft-versus-host reaction in allogeneic severe combined immunodeficiency recipients. This suggests that a mechanism operating in vivo, perhaps tolerance or migration pattern, attenuates the response of emigrants against antigens that did not induce their deletion in the thymus.

Abatacept↗

Does the extent of surgery have an impact on the survival of patients who receive postoperative radiation therapy for supratentorial low-grade gliomas?

We evaluate the impact of extent of surgery (EOS) on survival of patients with supratentorial nonpilocytic low-grade gliomas (LGG) treated with postoperative radiation therapy (PORT). Sixty-five patients with pathologically confirmed supratentorial nonpilocytic LGG (36 astrocytomas and 29 oligodendrogliomas) were treated with PORT after different extents of surgery: 12 gross total resections (GTR), 27 minimal or subtotal resections (MR/SR), and 26 biopsies (B). EOS was confirmed with postoperative imaging. The median radiation dose delivered was 5,940 cGy (range, 4,950-6,620 cGy). One of 12 patients (8%) in the GTR group and 12 of 53 patients (23%) in the less than GTR group demonstrated contrast enhancement. The median follow-up was 61 months (range 5-194 month). The 10-year overall survival (OS) was 82.5% and 32% for the GTR and the less than GTR groups, respectively (P = 0.0008). The corresponding 10-year disease-specific survival (DSS) was 90% and 41.4%%, respectively (P = 0.001). Multivariate analysis showed that only contrast enhancement and EOS were predictors for OS and DSS. Our data suggest that EOS correlates with OS and DSS in patients who have PORT. GTR should be the goal if technically achievable without causing significant morbidity, and its combination with PORT is compatible with long-term survival.

Adult↗

Mode of antiviral activity of water soluble components isolated from Elfvingia applanata on vesicular stomatitis virus.

A preparation of water soluble components (EA) was made from carpophores of Elfvingia applanata (Pers.) Karst and its in vitro antiviral activity on vesicular stomatitis virus [(Indiana serotype, VSV(IND)] was investigated by plaque reduction assay. EA exhibited potent antiviral activity on VSV(IND) growth and negligible cytotoxicity on Vero cells, 50% effective concentration (EC50) of 104 microg/ml and 50% cytotoxic concentration (CC50) of 3,793 microg/ml, respectively. Selectivity index (SI, CC50/EC50) of EA on Vero cell and VSV(IND) was about 36.5. EA did not display either a direct virucidal effect on VSV(IND) or induction of antiviral substance by Vero cells upon its treatment. Thus, the mode of antiviral activity of EA was studied at steps of viral adsorption onto cell. When both EA and virus were added to cell monolayers, titer of cell-free virus in culture supernatant increased in ca. 30-40% compared with that of control group and titer of cell-associated virus was 60-100% higher than that of control group. These results suggested that antiviral activity of EA on VSV(IND) might be due to the hindrance of viral entry to cells at either endocytosis or loss of envelope.

Animals↗

Serum ferritin as a serologic marker of activity in systemic lupus erythematosus.

To investigate the relationship between serum ferritin and disease activity in systemic lupus erythematosus (SLE), we enrolled 128 patients with SLE (18 males and 110 females). Twenty-eight patients (2 males and 26 females) with rheumatoid arthritis (RA) served as controls. The SLE patients were subdivided into three groups according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores: groups A (0-5), B (6-9), and C (> or =10). We prospectively evaluated 48 SLE patients before and after treatment. Serum ferritin and anti-dsDNA antibody were measured by radioimmunometric assay. C-reactive protein (CRP) was measured quantitatively by immunonephelometry. Complements 3 and 4 (C3 and C4) were measured by nephelometry. Serum levels of ferritin during the more active stage of SLE (group C) exceeded those of RA patients and patients at less active stages of SLE (groups A and B). There were no significant differences between RA patients and groups A and B. Serum ferritin was elevated especially in serositis and hematologic manifestation. In this prospective study, changes in SLEDAI scores before and after treatment correlated significantly with serum ferritin levels and inversely to C3 and C4 levels. We confirm that serum ferritin levels can be a useful marker of disease activity in SLE patients.

Adult↗

Emergence of YMDD motif mutant of hepatitis B virus during short-term lamivudine therapy in South Korea.

BACKGROUND/AIMS: The emergence of a YMDD mutant resistant to lamivudine therapy has been reported in patients with hepatitis B treated with long-term lamivudine therapy. However, it is not well known whether the YMDD mutant could be detected early in lamivudine therapy in hepatitis B virus (HBV) endemic areas. The aim of this study was to investigate the emergence of the YMDD mutant during short-term lamivudine therapy in South Korea. METHODS: We prospectively investigated the emergence of the YMDD mutant by the nested PCR assay using restriction fragment length polymorphism in 28 patients with chronic hepatitis B who were treated with 100 mg of lamivudine daily for 12 weeks. RESULTS: The YMDD mutant was detected in 17 (60.7%) out of 28 patients at week 12, and the only type of mutation found was the YIDD mutation. When we carried out the nested PCR serially in five patients, YIDD mutants were detected as early as 2 weeks by the nested PCR assay. The nested PCR results were in concordance with DNA sequencing in one patient's serial samples. CONCLUSIONS: YMDD mutants in HBV were detected within a few weeks during lamivudine therapy in South Korea, which suggests that the YMDD mutant may exist even before lamivudine therapy in HBV endemic areas.

Adult↗

Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells.

Acemannan, a major carbohydrate fraction of Aloe vera gel, has been known to have antiviral and antitumoral activities in vivo through activation of immune responses. The present study was set out to define the immunomodulatory activity of acemannan on dendritic cells (DCs), which are the most important accessory cells for the initiation of primary immune responses. Immature DCs were generated from mouse bone marrow (BM) cells by culturing in a medium supplemented with GM-CSF and IL-4, and then stimulated with acemannan, sulfated acemannan, and LPS, respectively. The resultant DCs were examined for phenotypic and functional properties. Phenotypic analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2, CD40 and CD54 confirmed that acemannan could induce maturation of immature DCs. Functional maturation of immature DCs was supported by increased allogeneic mixed lymphocyte reaction (MLR) and IL-12 production. The differentiation-inducing activity of acemannan was almost completely abolished by chemical sulfation. Based on these results, we propose that the adjuvant activity of acemannan is at least in part due to its capacity to promote differentiation of immature DCs.

Adjuvants, Immunologic↗

Diterpenoids from the leaves of Juniperus chinensis var. kaizuka.

Two diterpenoids based on novel carbon skeletons, namely, 8,19-dioxo-8,14-seco-chinan-14,11-olide (1) and 8-oxo-8,14-seco-abiet-12-en-14,19-dial (2), have been isolated, together with two new abietane diterpenoids, 13 beta,14 beta-epoxyabiet-7-en-19,6 beta-olide (3) and 7 beta-hydroxyabieta-8,11,13-trien-19-al (4), from the leaves of Juniperus chinensis. Their structures were determined by spectroscopic methods, including 2D NMR, and, in the case of 1, X-ray crystallographic analysis.

Crystallography, X-Ray↗

Late onset post-transplantation lymphoproliferative disease of recipient origin following cytogenetic relapse and occult autologous haematopoietic regeneration after allogeneic bone marrow transplantation for acute myeloid leukaemia.

A post-transplantation lymphoproliferative disease (PTLD) of recipient origin was identified in one of 376 consecutive cases of allogeneic bone marrow transplantation (BMT). This occurred in a 36-year-old woman who received an allogeneic BMT for acute myeloid leukaemia in relapse. At 15 months after BMT, recipient haematopietic and leukaemic cells were found in the bone marrow, which disappeared on withdrawal of immunosuppression. However, severe graft-versus-host disease (GVHD) necessitated the continuation of immunosuppression, leading to the occurrence of PTLD in the liver and lung 12 months afterwards. Fluorescence in situ hybridisation showed that the neoplastic cells were of recipient origin. Although the PTLD also responded completely to withdrawal of immunosuppression, the patient finally died from the complications of GVHD. This case of late onset PTLD post-BMT showed features similar to those in solid organ transplantation, in that the tumour was of recipient origin and responded well to the withdrawal of immunosuppression. Of further interest is that recipient lymphoid regeneration had accompanied autologous haematopoietic regeneration and become a target for subsequent neoplastic transformation.

Acute Disease↗