Search PubMed⌕ Search

Biomedical subjects

H C Lee

Publications and source records attributed to H C Lee.

At least 109 records · Page 6Linked to original sources

NAADP: An emerging calcium signaling molecule.

Cells possess multiple Ca(2+) stores and multiple messengers for mobilizing them. In addition to inositol trisphosphate and cyclic ADP-ribose, nicotinic acid adenine dinucleotide phosphate (NAADP), a metabolite of NADP, is shown to be a potent Ca(2+) signaling molecule in both invertebrate and mammalian cells. This article summarizes the recent results of this newly discovered Ca(2+) signaling mechanism and explores the implications of the apparent proliferation of Ca(2+) messengers.

Animals↗

Possibility of wound dressing using poly(L-leucine)/poly(ethylene glycol)/poly(L-leucine) triblock copolymer.

ABA-type block copolymers (abbreviated as LEL) composed of poly(L-leucine) (PLL) as the A component and poly(ethylene glycol) (PEG) as the B component were synthesized by ring-opening polymerization of L-leucine N-carboxyanhydride initiated by primary amino group located at both ends of PEG chain. A silver sulfadiazine (AgSD)-impregnated wound dressing of sponge type was prepared by the lyophilization method. Morphological structure of this wound dressing by scanning electron microscopy was observed to be composed of a dense skin layer and a porous inner layer. Equilibrium water content of LEL wound dressing increased with an increase in PEG content in the block copolymer due to the hydrophilicity of PEG. AgSD release from AgSD-impregnated wound dressing in PBS buffer (pH = 7.4) was dependent on PEG content in the block copolymer. Release of AgSD was increased in proportion to the PEG content in the copolymer. Antibacterial capacity of AgSD-impregnated wound dressing was examined in agar plate against Pseudomonas aeruginosa and Staphylococcus aureus. It was found that the suppression of bacterial proliferation in the wound dressing was dependent upon the PEG content. In cytotoxicity test, cell damage did not occur by the release of AgSD from the LEL sponge matrix of AgSD-medicated wound dressing. In in vivo test, granulous tissue formation and wound contraction for the AgSD- and dehydroepiandrosterone-impregnated LEL-2 wound dressing were faster than for any other groups.

Animals↗

Identification of glucokinase mutation in subjects with post-renal transplantation diabetes mellitus.

Mutations in the glucokinase (GCK) gene are considered to be a possible cause of maturity-onset diabetes of the young. The purpose of this study was to evaluate the contribution of this gene to the development of post-renal transplantation diabetes mellitus (PTDM). Identification of the GCK mutation was attempted in 58 selected renal allograft recipients with PTDM and 45 normal controls. The exons in the GCK gene were examined using polymerase chain reaction (PCR), followed by an analysis of single-stranded DNA conformational polymorphism (SSCP). The abnormal bands were then confirmed by DNA sequencing analysis. The family members of the patients affected with GCK mutation were also examined. Two of the 58 PTDM patients (3. 4%) were found to have GCK mutations. One had the mutation on exon 5 and the other on intron 7. One control subject had the mutation on intron 9. The mutation on exon 5 was identified as a substitution of CCT (proline) for CTT (leucine) at codon 164, which has never been reported before. The family members of the PTDM patient with a mutation on exon 5 were analyzed by PCR, followed by SSCP, and two of them had the same mutation. The abnormal band seen on SSCP analysis of exon 7 was identified as the C-->T substitution at the 39th nucleotide in intron 7. Two of the family members also displayed the same bands on the SSCP. One of the 45 normal controls had a known polymorphism located at the 8th nucleotide in intron 9. We found a GCK mutation on the exon in subjects with PTDM and we speculate that this mutation may be one of the possible contributing factors of PTDM, although variations of the GCK gene are not common causes of PTDM.

Adult↗

Synthesis, radiolabeling, and biodistribution of putative metabolites of iodoazomycin arabinoside.

Scintigraphic evaluation of patients with advanced oncological disease showed uptake of radioactivity in the brain following administration of the hypoxic imaging agent 123I-iodoazomycin arabinoside (123I-IAZA). Three proposed metabolites of IAZA--methyl 5-deoxy-5-iodo-D-arabinofuranoside, methyl 2,3-di-O-acetyl-5-deoxy-5-iodo-alpha-D-arabinofuranoside, and 1-(5-deoxy-5-iodo-alpha-D-arabinofuranosyl)-2-aminoimidazole (IAIA)--were synthesized, radiolabeled with 125I, and investigated in normal and tumor-bearing murine models for their contribution to this unusual phenomenon. The three compounds were readily radiolabeled by melt or solvent exchange procedures. Biodistribution data indicated rapid blood clearance, rapid excretion, and little tissue accumulation in the brain. IAIA showed significant tumor to blood ratios at 4 h (4.3:1) and liver to blood ratios at 24 h (30:1).

Animals↗

Pilonidal disease in Singapore: clinical features and management.

BACKGROUND: Pilonidal disease has not been well documented in Asian people. The aims of the present study were to investigate any variations in the clinical features and effectiveness of various surgical treatments in such a population. METHODS: A prospectively collected computerized database of 61 consecutive patients admitted to a specialist colorectal unit over a 9-year period was studied. The five methods of surgical treatment used during this period (incision and drainage; laying open; marsupialization; primary closure; and the flap procedure) were compared. RESULTS: There were 38 men and 23 women with a mean age of 27+/-1.02 years. Pilonidal disease was significantly more common among the Indian people (52.5% of patients) than the other ethnic races in the Singaporean community (P < 0.001). Chronic discharging sinuses were the most common presentation (93.4%). There were no differences between the various surgical techniques employed with regard to the time required for wound healing (mean: 48+/-21 days) and recurrence rates (4/61, 6.6%). Wound dehiscence after primary wound closure (10%) and flap procedures (42%) meant that the overall healing rate was not faster than when the wound was just laid open. Furthermore, flap procedures required a longer hospitalization than other procedures (P = 0.005). CONCLUSION: Pilonidal disease was more common among Indian people, the more hirsute among the Singaporean population. Primary closure and flap procedure did not improve overall wound healing because of dehiscence.

Adult↗

Impact of inadequate fine-needle aspiration cytology on outcome of patients with palpable breast lesions.

BACKGROUND: The purpose of the present study was to assess the impact of inadequate fine-needle aspiration cytology (FNAC) breast specimens on the outcome of patients with a palpable breast lesion. METHODS: A retrospective review was carried out of inadequate FNAC specimens from the Department of General Surgery, Singapore General Hospital in 1997. RESULTS: One hundred and thirty-eight (16.6%) of 831 FNAC specimens were reported inadequate, and these form the study group. Outcome analysis was divided into benign on excision biopsy (n = 38; 29.4%); benign on repeat FNAC or trucut biopsy (n = 6; 4.7%); benign on follow up (n = 46; 35.7%); malignant on histology (n = 11; 8.5%); and lost to follow up (n = 28; 21.7%). The 11 cases with breast cancer were further analysed. The mean time to treatment was 88.3 days for three patients whose tumours were not clinically suspicious of malignancy versus 20 days for six patients who were diagnosed with cancer clinically from the onset. One patient with cancer refused treatment and one absconded from treatment only to return 7 months later. CONCLUSION: Breast cancer was present in 8.5% of the inadequate FNAC specimens. When clinical suspicion of malignancy is high, an excision biopsy is advised in patients with inadequate FNAC specimens. If properly managed with triple tests and good clinical judgement, the inadequate FNAC specimens do not delay treatment in patients with breast cancer.

Adult↗

Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea.

It has been suggested that hepatitis B e antigen (HBeAg) seroconversion after lamivudine therapy is durable in Caucasians with chronic hepatitis B (CHB). However, little is known whether it is also durable in endemic areas of hepatitis B virus (HBV) infection. We evaluated the posttreatment durability of lamivudine-induced HBeAg seroconversion and the predictive factors for relapse in Korean patients with CHB. We retrospectively analyzed 98 HBeAg-positive patients with CHB who were treated with lamivudine between August 1996 and December 1997. Lamivudine was given at a dose of 150 mg per day. After HBeAg seroconversion, lamivudine was continued for an additional 2 to 4 months, and posttreatment monitoring continued for up to 24 months. HBeAg seroconversion was achieved in 34 of the 98 patients (34.7%). The mean duration of treatment in these seroconverters was 9.3 +/- 3.0 months. During the follow-up period, the cumulative relapse rates at 1 year and 2 years posttreatment were 37.5% and 49.2%, respectively. Most relapses were accompanied by elevation of serum alanine transaminase (94%) and reappearance of HBeAg (81%). Pretreatment serum HBV DNA levels and the duration of additional lamivudine therapy after HBeAg seroconversion were 2 independent predictive factors for posttreatment relapse. In conclusion, lamivudine-induced HBeAg seroconversion was not durable in this endemic area. And the duration of additional lamivudine therapy after HBeAg seroconversion significantly affected the posttreatment relapse. Further studies are needed to determine the duration of lamivudine and to elucidate the cause of high relapse after HBeAg seroconversion in endemic areas of HBV.

Adult↗

Clinical features and therapeutic implications of 104 episodes of monomicrobial Aeromonas bacteraemia.

OBJECTIVES: Aeromonas bacteraemia is not a common infectious disease, but can cause a grave outcome in infected cases. In this study, clinical presentations and prognostic factors of cases of monomicrobial Aeromonas bacteraemia were analysed. Also, the impact of beta-lactam and aminoglycoside in combination and of emerging cephalosporin-resistance during therapy was discussed. METHODS: From 1989 to 1998 in a medical centre in southern Taiwan, those cases with monomicrobial Aeromonas bacteraemia were included for study. RESULTS: A total of 104 episodes of monomicrobial Aeromonas bacteraemia, accounting for 74% of all Aeromonas bacteraemia, were encountered. The infections usually occurred in the patients with hepatic cirrhosis (54%) or malignancy (21%) and were community-acquired (74%). Cases of community-acquired bacteraemia were more likely to have cirrhosis, a high severity score at onset, and a worse prognosis than those of nosocomial bacteraemia did and nosocomial isolates were less susceptible to cefoxitin and cefotaxime. Forty-three percent of cases had a concomitant infection focus, such as primary peritonitis, invasive cellulitis or necrotizing fasciitis, biliary tract or burn wound infections. Crude fatality rate within 2 weeks after the onset was 30%. Secondary bacteraemia and a higher severity score ( > or = 4) for illness at the first presentation were independently associated with a fatal outcome. The therapeutic superiority of beta-lactam and aminoglycoside in combination cannot be demonstrated in patients with Aeromonas bacteraemia. Cefotaxime resistance emerged in 3.4% of 58 patients treated with a cephalosporin for at least 72 h. None of the community-acquired isolates, but one-quarter of the nosocomial isolates, were resistant to cefotaxime. CONCLUSIONS: Aeromonas bacteraemia usually occurred in patients with liver cirrhosis or malignancy, and heralded a poor prognosis, especially while associated with a relevant infectious source or with a higher severity score at presentation. The superiority of aminoglycoside and beta-lactam in combination cannot be demonstrated while treating those patients, and the emergence of antimicrobial resistance to cephalosporin was a rare event during cephalosporin therapy. Thus, a broad-spectrum cephalosporin remains one of the antimicrobial alternatives for invasive community-acquired Aeromonas infections.

Adolescent↗

Modulation of CD157 expression in multi-lineage myeloid differentiation of promyelocytic cell lines.

CD157/BST-1 is expressed on mature myeloid cells but not on their precursors in vivo. Also CD38, a homologous gene to CD157, is upregulated in promyelocytic HL-60 cells by the monocyte and granulocyte differentiation-inducing 1alpha,25dihydroxyvitamin D3 (VD3) and all-trans retinoic acid (ATRA), respectively. We have examined whether CD157 expression is upregulated when the promyeloid HL-60 and/or U937 cells are induced to differentiate into mature phenotypes in vitro. VD3 treatment irreversibly upregulated the expression of CD157 in HL-60 cells but not in U937 cells in a time- and concentration-dependent manner when analyzed by flow cytometry, immunoblotting and/or RT-PCR. Different monocyte and granulocyte lineage inducers induced CD157 expression to varying extents while the macrophage differentiation-inducing phorbol 12-myristate 13-acetate (PMA) induced its down-regulation. Time-kinetics of VD3 treatment of HL-60 cells showed that the appearance of CD157 and CD11b (a differentiation marker) antigens were not substantial up to 24 hours but increased subsequently although the appearance of CD38 became significant within 6 hours. Two-color staining of VD3-treated HL-60 cells displayed an apparently linear correlation between CD157 and CD11b expression. Dibutyryl cAMP (cAMP agonist) and forskolin (cAMP-increasing agent) augmented the VD3-dependent induction of CD157 and CD11b expression while PGE1 (cAMP-decreasing agent) inhibited it, suggesting the involvement of a cAMP-dependent mechanism in VD3-induced CD157 upregulation. Co-treatment of HL-60 cells with VD3 plus TNF-alpha or ara-C produced an additive effect on CD157 upregulation. The upregulated CD157 in the VD3-differentiated HL-60 cells was able to activate CD157-dependent tyrosine kinase signal when cross-linked with anti-CD157 antibody.

ADP-ribosyl Cyclase↗

Chronic alcohol intake differently influences glucose metabolism according to nutritional status.

We investigated the potential different effects of a chronic alcohol intake on glucose metabolism according to nutritional status in growing rats. Eighty weanling 4-week-old male Sprague Dawley rats were fed with low (5%, wt/wt) or control (22%) protein diet for 8 weeks. Each group was subdivided into alcohol (5 g/kg(-1) x day(-1)) or saline gavage rats during the last 4 weeks. At 12 weeks of age, we measured the weights of the body, pancreas, and epididymal fat; glycogen synthase activity of gastrocnemius muscle; and insulin content of the pancreas. We performed an ip glucose tolerance test and a euglycemic hyperinsulinemic clamp test. Weight gain was almost arrested in protein-deficient rats. The relative weight and insulin content of the pancreas and glycogen synthase activity were not different among the four groups, but the relative amount of epididymal fat decreased only in protein-deficient saline rats. Insulin response after glucose challenge and glucose disposal rate during the euglycemic clamp were both markedly decreased in protein-deficient saline rats, but not changed in protein-deficient alcohol rats. Protein-deficiency per se causes deterioration both in insulin secretory function and in sensitivity, but these defects are protected by a chronic alcohol intake. In a protein-sufficient state, alcohol intake gives no additional effects on glucose metabolism. Therefore, according to individual nutritional status, the metabolic effect of alcohol intake appears differently.

Adipose Tissue↗

Functional visualization of the separate but interacting calcium stores sensitive to NAADP and cyclic ADP-ribose.

Cells possess multiple Ca(2+) stores and their selective mobilization provides the spatial-temporal Ca(2+) signals crucial in regulating diverse cellular functions. Except for the inositol trisphosphate (IP(3))-sensitive Ca(2+) stores, the identities and the mechanisms of how these internal stores are mobilized are largely unknown. In this study, we describe two Ca(2+) stores, one of which is regulated by cyclic ADP-ribose (cADPR) and the other by nicotinic acid adenine dinucleotide phosphate (NAADP). We took advantage of the large size of the sea urchin egg and stratified its organelles by centrifugation. Using photolysis to produce either uniform or localized increases of cADPR and NAADP from their respective caged analogs, the two separate stores could be visually identified by Ca(2+) imaging and shown to be segregated to the opposite poles of the eggs. The cADPR-pole also contained the IP(3)-sensitive Ca(2+) stores, the egg nucleus and the endoplasmic reticulum (ER); the latter was visualized using Bodipy-thapsigargin. On the other hand, the mitochondria, as visualized by rhodamine 123, were segregated to the opposite pole together with the NAADP-sensitive calcium stores. Fertilization of the stratified eggs elicited a Ca(2+) wave starting at the cADPR-pole and propagating toward the NAADP-pole. These results provide the first direct and visual evidence that the NAADP-sensitive Ca(2+) stores are novel and distinct from the ER. During fertilization, communicating signals appear to be transmitted from the ER to NAADP-sensitive Ca(2+) stores, leading to their activation.

Adenosine Diphosphate Ribose↗

Spectroscopic properties of fluoroquinolone antibiotics and nanosecond solvation dynamics in aerosol-OT reverse micelles.

Among fluoroquinolone antibiotics, ofloxacin (OFL) and norfloxacin (NOR) have piperazinyl groups but flumequine (FLU) does not have this substitutent. The emission spectra of OFL and NOR are strong, broad structureless bands with large Stokes' shifts in water but the emission intensities are very weak in organic solvents. Thus we find that these compounds exist as different chemical species in various solvents. A continuous red shift in the emission bands for OFL and NOR is observed as the water concentration within the aerosol-OT (AOT; sodium 1,4-bis[2-ethylhexyl]sulfosuccinate) micelle increases or temperature of this solution rises. From the fluorescence anisotropy measurements of OFL and NOR, we assume the intramolecular charge transfer after excitation from the nitrogen of the piperazinyl group to the keto oxygen. Theoretical calculations further support this observation. Multifrequency phase and modulation experiments and time-resolved emission spectra clearly show the occurrence of intramolecular charge transfer and the subsequent nanosecond water reorganization around OFL or NOR in the AOT micelle. Upon increasing the water concentration within the AOT micelle, the relaxation rate increases because of the large amount of free water. The emission spectra of FLU do not exhibit any significant response to the physical properties of their environment.

Anti-Infective Agents↗