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Biomedical subjects

C S Lee

Publications and source records attributed to C S Lee.

At least 19 recordsLinked to original sources

Isolation and phylogenetic analysis of H1N1 swine influenza virus isolated in Korea.

A swine influenza H1N1 virus was isolated from a pig during a severe outbreak of respiratory disease in Korea. All genes of the H1N1 isolate, including hemagglutinin (HA), neuraminidase (NA), matrix (M), nucleoprotein (NP), non-structural (NS), PA, PB1 and PB2, were of swine origin. Also, all these genes showed a close phylogenic relationship with those of H1N1 viruses previously isolated from pigs in the United States. These results suggest that North American swine influenza virus has actually been transmitted to pigs in Korea.

Animals↗

Modulation of 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells by K(ATP) channel block.

The present study investigated the effect of 5-hydroxydecanoate, a selective mitochondrial K(ATP) channel blocker, on the cytotoxicity of neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) in differentiated PC12 cells. 5-Hydroxydecanoate and glibenclamide (a cell surface and mitochondrial K(ATP) channel inhibitor) reduced the MPP(+)-induced cell death and GSH depletion and showed a maximal inhibitory effect at 5 and 10 microM, respectively. Addition of 5-hydroxydecanoate attenuated the MPP(+)-induced nuclear damage, changes in the mitochondrial membrane permeability and increase in the reactive oxygen species formation in PC12 cells. The results show that 5-hydroxydecanote may prevent the MPP(+)-induced viability loss in PC12 cells by suppressing formation of the mitochondrial permeability transition, leading to the cytochrome c release and caspase-3 activation. This effect appears to be accomplished by the inhibitory action on the formation of reactive oxygen species and the depletion of GSH. The blockade of mitochondrial K(ATP) channels seems to prevent the MPP(+)-induced neuronal cell damage.

1-Methyl-4-phenylpyridinium↗

Geometric and excited-state properties of 1,4-bis(benzothiazolylvinyl)benzene interacting with 2,2',2' '-(1,3,5-phenylene)tris[1-phenyl-1H-benzimidazole] studied by a density-functional tight-binding method.

The energetics and luminescent property of a guest molecule, 1,4-bis(benzothiazolylvinyl)benzene (BT), interacting with a host molecule, 2,2',2' '-(1,3,5-phenylene)tris[1-phenyl-1H-benzimidazole] (TPBI), in organic light-emitting diodes are studied by performing excited-state calculations using a time-dependent density-functional tight-binding method complemented with dispersion energy. It is found that the overlap between the TPBI emission and the BT absorption spectra shows an efficient energy transfer from the host molecule to the guest molecule when they are excited. The planar BT molecule becomes distorted when it is mixed with TPBI, resulting in a blue luminescence around 475 nm. The separation of the TPBI + BT mixture on a graphite surface is found to be energetically favorable, consistent with experimental observation.

Journal Article↗

7-Ketocholesterol enhances 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells.

The present study investigated the promoting effect of oxysterol 7-ketocholesterol against the cytotoxicity of 1-methyl-4-phenylpyridinium (MPP(+)) in differentiated PC12 cells. 7-Ketocholesterol significantly enhanced the MPP(+)-induced nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species and depletion of GSH. N-Acetylcysteine, ascorbate, trolox, carboxy-PTIO and Mn-TBAP reduced the cytotoxic effect of MPP(+) in the presence of 7-ketocholesterol. The results indicate that 7-ketocholesterol shows a synergistic effect against the cytotoxic effect of MPP(+). 7-Ketocholesterol may enhance the MPP(+)-induced viability loss in PC12 cells by promoting the mitochondrial membrane permeability change, release of cytochrome c and subsequent activation of caspase-3, which is associated with the increased formation of reactive oxygen species and depletion of GSH. The findings suggest that 7-ketocholesterol as a promoting agent for the formation of mitochondrial permeability transition may enhance the toxic neuronal cell injury.

Animals↗

Mitochondria are impaired in the adipocytes of type 2 diabetic mice.

AIMS/HYPOTHESIS: The aim of this study was to confirm a link between mitochondrial dysfunction and type 2 diabetes. MATERIALS AND METHODS: Cellular levels of mitochondrial proteins, cellular mitochondrial DNA content, and mitochondrial function and morphology were assessed by MitoTracker staining and electron microscopy, in white adipose tissue of 12-week-old male wild-type, obese (ob/ob), and diabetic (db/db) mice. RESULTS: Levels of mitochondrial proteins were found to be very similar in the livers and muscles of all the mice studied. However, levels were greatly decreased in the adipocytes of db/db mice, but not in those of the wild-type and ob/ob mice. Levels of mitochondrial DNA were also found to be considerably reduced in the adipocytes of db/db mice. MitoTracker staining and under electron microscopy revealed that the number of mitochondria was reduced in adipocytes of db/db mice. Respiration and fatty acid oxidation studies indicated mitochondrial dysfunction in adipocytes of db/db mice. Interestingly, there was an increase in mitochondria and mitochondrial protein production in adipocytes of db/db mice treated with rosiglitazone, an agent that enhances insulin sensitivity. CONCLUSIONS/INTERPRETATION: Taken together, these data indicate that mitochondrial loss in adipose tissue is correlated with the development of type 2 diabetes.

Adipocytes↗

Degeneration and apoptosis of endometrial cells in the bitch.

The relationships between changes in plasma progesterone concentrations, degeneration of the luminal epithelium, the occurrence of apoptosis of endometrial cells and endometrial leucocyte populations in the bitch were determined. Mature bitches (n = 15) were euthanized and necropsied when in diestrus (Days 7-75, n = 12) or in anestrus (Days 10, 32 and 53). Degeneration of the luminal epithelium was observed in bitches in late diestrus (Days 38-75, n = 5) when plasma progesterone concentrations were decreasing and in anestrus (Days 10 and 32, n = 2) when plasma progesterone concentrations were < 0.5 ng/mL. Endometrial leucocyte populations increased after degeneration of the luminal epithelium (around Day 42 of diestrus). Apoptosis was mainly observed in the basal glandular epithelial cells and endothelial cells of blood capillaries in all except anestrous bitches. Very few apoptotic cells were found in the superficial glandular epithelial cells and stromal cells. Higher apoptotic indices were detected in the basal glandular epithelium on Days 12-42 of diestrus than at other stages. Therefore, apoptosis of glandular basal epithelial cells occurred mainly in early diestrus, degeneration of cells of the luminal epithelium occurred from mid-diestrus to early anestrus, and the increase in leucocyte numbers may have been a consequence and not a cause of luminal epithelial degeneration.

Anestrus↗

The roles of progestagen and uterine irritant in the maintenance of cystic endometrial hyperplasia in the canine uterus.

Cystic endometrial hyperplasia (CEH) was induced in the left uterine horns of 14 mature ovariectomised greyhound bitches with an intra-luminal silk suture (uterine irritant) and treatment with estradiol benzoate and megestrol acetate (to simulate stages of a normal canine estrous cycle). Right uterine horns served as suture-free controls. From Day 30 of simulated diestrus, bitches received treatments of suture removal (n = 4), progestagen withdrawal (n = 5) or both (n = 5). Necropsies were performed 3 or 9 weeks later. At 3 weeks, severe cystic endometrial hyperplasia was present in all (6/6) left horns and in no (0/6) right horns. At 9 weeks, the left horns in 5/6 of bitches subjected to progestagen-withdrawal had recovered (in varying degrees) from cystic endometrial hyperplasia, whereas no recovery was evident in the left horns of bitches (n = 2) that continued to receive progestagen. This study demonstrated that: (i) cystic endometrial hyperplasia was reversible upon withdrawal of progestagen; (ii) progestagen maintained cystic endometrial hyperplasia in the presence or absence of irritant; and (iii) persistent endometrial irritation in the absence of progestagen may not maintain cystic endometrial hyperplasia.

Animals↗

Alteration of foot temperature in diabetic neuropathy: is it another piece of puzzle?

Poor glycaemic control and the duration of diabetes mellitus are known to accelerate development and progression of neuropathy. Diabetic co-morbidities: hypertension and hyperlipidaemia, have been postulated to associate with development of neuropathy. A diabetic foot with low temperature and frequent exposure to low temperature environment has recently been hypothesized to be at higher risk to develop early neuropathy. This cross-sectional study is undertaken to identify risk factors for diabetic neuropathy and the association between foot temperature and development of diabetic neuropathy by using simple clinical examination in the outpatient setting. From April 18, to April 30, 2005, universal sampling method was used to select 134 diabetic patients (type 1 or type 2 for >1 year) with peripheral neuropathy. Excluded are those with chronic alcoholism, drug-induced neuropathy, dietary history of vitamin B deficiency and family history of porphyria and hereditary sensorimotor neuropathy. The patient's duration of diabetes, glycaemic control status and the presence of co-morbids: hypertension and hyperlipidemia, were recorded. The temperature of the foot was measured by using thermo buddy. Of 134 patients representing Malaysian ethnic distribution with an equal number of males and females, 20.1% were in the age group of 61 to 65 years and, 85.1% and 67.9% belonged to lower socioeconomic and educational groups respectively. Associations between diabetic neuropathy and glycaemic control (p = 0.018) and duration of diabetes (p < 0.05) were significant. However, hypertension, hyperlipidaemia and low foot temperature were not significantly associated with development of diabetic neuropathy. Poor glycaemic control is significantly associated with diabetic neuropathy. Foot temperature alteration is merely an effect of autonomic neuropathy with a cold foot is attributed to co-existing peripheral arterial disease.

Adult↗

Necrotizing fasciitis of the lower limb: an outcome study of surgical treatment.

Necrotizing fasciitis is a limb- and life-threatening rapidly spreading infection affecting the deep fascia with secondary necrosis of the subcutaneous tissue. It requires immediate medical attention and emergency surgery to prevent morbidity and death. This study was undertaken to determine its co-morbidity and risk factors affecting the outcome of its surgical treatment. This is a retrospective review of 36 cases of necrotizing fasciitis of the lower limb treated in our center between 1998 and 2002. Only 19% of the cases were correctly diagnosed upon admission and 48.6% were initially diagnosed as 'cellulitis'. Diabetes mellitus was the most common co-morbid. Pseudomonas, Staphylococcus, Streptococcus and Enterobactericae were the common pathogens isolated. Ten patients (27.8%) had major amputation as part of radical debridement. The overall mortality rate was 36% with laboratory parameters: high serum urea and creatinine, and low haemoglobin levels were predictors for higher mortality. Poor white cell response which is common in diabetic patients and a delay in surgical debridement were. notable attributes to a higher mortality. Necrotizing fasciitis is a serious infection associated with significant morbidity and mortality. A poor white blood cell response, high serum urea and creatinine, and low haemoglobin level were the predictors for mortality. Early diagnosis and prompt treatment are of paramount importance in the treatment of this infection.

Adult↗

Integrated microfluidic UV absorbance detector with attomol-level sensitivity for BSA.

An integrated UV absorbance detection system employing a novel silicon-in-plastic technology to seamlessly integrate bare UV photodiode chips into polymer microfluidic systems has been developed. Detection platforms fabricated using this approach exhibit exceptionally low concentration and mass detection limits down to 15 nM and 9.8 amol, respectively, for bovine serum albumin (BSA) as a model protein. In addition to providing high sensitivity, sub-nanoliter detection volumes are enabled by the use of direct photodiode integration. The fabrication methodology is detailed, and system performance metrics including detection limits, detection volume, dynamic range, and linearity are reported.

Animals↗

Calcium/poly(9,9-dioctylfluorene) interaction: a theoretical study.

The geometric and electronic structures of poly(9,9-dioctylfluorene) (PFO) oligomer interacting with Ca atoms were studied using Møller-Plesset perturbation theory. A weak interaction with little charge transfer and with a relatively long Ca-C distance (about 4.0 Angstrom) was found when only one Ca atom was attached to a PFO unit. However, when two Ca atoms were adsorbed at a PFO unit, a strong interaction with a shorter Ca-C distance (about 2.67 Angstrom) took place with considerable charge transfer from the Ca atom to the PFO, resulting in significant deformation in the backbone of the PFO oligomer. In the latter case, the frontier orbitals of the PFO were modified. However, the deformed PFO and its modified frontier orbitals could be recovered when oxygen was added, which is in good agreement with experimental observation.

Journal Article↗

Molecular orientation and film morphology of pentacene on native silicon oxide surface.

The growth morphology and mechanism of pentacene films on native Si oxide surface have been studied by using high-resolution electron energy loss spectroscopy (HREELS), X-ray diffraction (XRD), and atomic force microscopy (AFM). Despite the good agreement between our own and the reported XRD results, the previous XRD interpretation that the pentacene molecules are tilt-standing on the substrate cannot explain our HREELS data. The HREELS results show that a substantial portion of the first two layers of pentacene molecules are tilted-standing or randomly oriented, whereas the upper-layer molecules are mostly lying flat to the substrate. AFM reveals that the first two layers of molecules form a flat and smooth surface, but the upper layers show a rough terrace structure with a mean-square roughness equal to the average thickness (without counting the first two layers). This relationship is explained by a theoretical model which assumes the pentacene molecules to remain on a particular molecule layer after arrival. The observed film growth morphology may have significant implication on the performance of electronic devices based on pentacene thin films. A plausible explanation was proposed for the discrepancy between the HREELS-indicated and the XRD-derived molecular orientations.

Journal Article↗

Prognostic significance of DNA quantification by flow cytometry in ovarian tumors.

OBJECTIVE: The objective of our study is to evaluate prognostic significance of DNA quantification by flow cytometry in ovarian tumor. METHODS: A prospective analysis was performed on 56 ovarian tumor patients treated in the Yonsei Medical Center from Feb. 2000 to Jan. 2003. RESULTS: Regarding the association between tumor grade and the DNA quantitative analysis, as tumor grade increased, the quantity of aneuploid cells and S-phase fraction (SPF) increased. In addition, SPF was increased significantly in the advanced staged patients (P=0.04) and SPF was significantly increased in aneuploid tumors (P=0.03). The overall survival rate was poor for patients with aneuploid tumors and for patients with tumors showing over SPF (10%). CONCLUSION: Our data demonstrated that the prognosis was poor for patients with aneuploid cancers or increased SPF. Therefore, DNA quantification by flow cytometry may provide important information for predicting the prognosis of the disease.

Aneuploidy↗

Gene expression profiling in breast cancer: towards individualising patient management.

Breast cancer is a complex and clinically heterogeneous disease. The increase in knowledge of breast cancer biology has led to a number of clinical advances in the treatment of breast cancer, most notably the implementation of widespread mammography screening and advances in adjuvant treatment of early-stage disease. In the last 20 years, arrays of potential prognostic and/or predictive markers of breast cancer have been analysed. However, relatively few have proven to be clinically useful. To date, the only widely accepted markers for routine use in breast cancer are the oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor, HER-2 (c-erbB2/neu). Expression microarray technology and laser capture microdissection have now been employed to further our understanding of the molecular pathogenesis of breast cancer. Recently reported advances in array technology and RNA amplification methods are having a considerable impact in this field, allowing the analysis of pre-malignant and pre-invasive lesions. A number of studies have identified prognostic and predictive gene 'signatures', whose prediction of disease outcome and response to treatment is superior to conventional prognostic indicators. Despite major technological advances, a number of confounding issues remain concerning the potential clinical utility of gene expression profiling, including differences in study design, patient selection, array technology, chemistry, and methods of analysis. It seems likely, however, that following careful 'hypothesis driven' validation studies and clinical trials, expression profiling will be applied in the future to identify patient-specific disease profiles and provide rationale for individualised treatment. This review focuses on the current use and future potential of microarray profiling in breast cancer.

Breast Neoplasms↗

Molecular cloning and characterization of full-length cDNAs encoding a novel high-molecular-weight Dermatophagoides pteronyssinus mite allergen, Der p 11.

BACKGROUND: Dermatophagoides pteronyssinus (Dp) and D. farinae (Df) mites are the most important source of indoor aeroallergens. Most Dp mite allergens identified to date have relatively low molecular weights (MWs). Identification of high-MW mite allergens is a crucial step in characterizing the complete spectrum of mite allergens and to provide appropriate tools for diagnostic and therapeutic application. METHODS: The full-length Der p 11 cDNA clone was isolated using cDNA library immunoscreening, the 5'-3' rapid amplification of cDNA ends (RACE) system and polymerase chain reactions (PCR). The whole cDNA insert and its PCR-derived DNA fragments (p1 to p4) were generated and expressed in the Escherichia coli expression system. The allergenicity of the recombinant protein and its peptide fragments was examined by IgE immunodot assays. The IgE-binding reactivity of rDer p 11 was analyzed in the serum of 50 asthmatic children with positive reactivity to Dp mite extract. Its recombinant peptide fragments were also examined by immunodot assays in 30 mite-allergic children. RESULTS: Der p 11 cDNA consists of a 2625-bp open reading frame encoding a 103-kDa protein with 875 amino acids. It exhibits significant homology with the paramyosin of other invertebrates. The protein sequence alignment of this newly identified Dp mite allergen (denominated as Der p 11) revealed over 89% identity with Der f 11 and Blo t 1. Among 50 Dp-sensitive asthmatic children, rDer p 11 showed positive IgE-binding reactivity to 39 patients (78%). Using immunodot assays, multiple human IgE-binding activities were demonstrated in all four fragments of Der p 11. Using immunoblot assays, the dominant IgG-binding epitope for monoclonal antibody (mAb642) was located in fragment p3 only. In immunoblot assays, cross-inhibition between rDer p 11 and rDer f 11 was up to 73-80% at concentrations of 100 microg/ml. CONCLUSIONS: This study confirms that the newly identified recombinant Der p 11 is a novel and important high-MW Dp mite allergen for asthmatic children. Our data also indicates that human IgE-binding major epitopes are scattered over the entire molecule of Der p 11.

Adolescent↗

Stromal CD10 expression in mammary fibroadenomas and phyllodes tumours.

BACKGROUND/AIMS: CD10 (CALLA) has recently been reported to be expressed in spindle cell neoplasia, and has been used to differentiate endometrial stromal sarcoma from leiomyoma and leiomyosarcoma. In the breast, myoepithelial cells express CD10, but there are few studies of the expression of CD10 in mammary fibroepithelial lesions. METHODS: Stromal CD10 expression was studied in 181 mammary phyllodes tumours (102 benign, 51 borderline malignant, and 28 frankly malignant) and 33 fibroadenomas using immunohistochemistry, to evaluate whether differences in expression correlated with the degree of malignancy. RESULTS: There was a progressive increase in the patients' age and tumour size, from fibroadenoma to phyllodes tumours with an increasing degree of malignancy (p < 0.001). Stromal CD10 expression was positive in one of 33 fibroadenomas, six of 102 benign phyllodes tumours, 16 of 51 borderline malignant phyllodes tumours, and 14 of 28 frankly malignant phyllodes tumours. The difference was significant (p < 0.001) and an increasing trend was established. Strong staining was seen in subepithelial areas with higher stromal cellularity and activity. Stromal CD10 expression had a high specificity (95%) for differentiating between benign lesions (fibroadenomas and benign phyllodes tumours) and malignant (borderline and frankly malignant) phyllodes tumours. CONCLUSIONS: CD10 may be a useful adjunct in assessing malignancy in mammary fibroepithelial lesions.

Adolescent↗

Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour.

BACKGROUND: Nitric oxide synthase (NOS), particularly endothelial and inducible forms (e/i-NOS), are expressed in various cancers, including breast cancer. In mammary fibroepithelial lesions, NOS expression in stromal cells has been reported to be lower in fibroadenomas than in phyllodes tumours. AIMS: To investigate NOS expression in phyllodes tumours of varying degrees of malignancy. METHODS: One hundred and sixty seven mammary phyllodes tumours (97 benign, 47 borderline malignant, and 23 frankly malignant) were evaluated for e-NOS and i-NOS expression by immunohistochemistry. Correlations with previously reported expression of stromal vascular growth factor (VEGF) and microvessel density were also performed. RESULTS: Stromal expression of e-NOS was absent, weak, moderate, and strong in 43%, 31%, 13%, and 13% of benign tumours; 17%, 26%, 13%, and 44% of borderline malignant tumours; and 17%, 35%, 13%, and 35% of frankly malignant tumours, respectively. Stromal expression of i-NOS was 77%, 18%, 4%, and 1% in benign tumours; 42%, 28%, 19%, and 11% in borderline malignant tumours; and 43%, 13%, 26%, and 18% in frankly malignant tumours, respectively. Stromal expression of both i-NOS and e-NOS was significantly different between the benign and malignant (borderline and frank) groups of phyllodes tumours (p < 0.0001). Furthermore, the expression of i-NOS correlated with stromal VEGF expression and microvessel density. The expression of NOS in the epithelial cells was strong, and showed no differences between the different groups of tumours. CONCLUSIONS: Higher stromal expression of NOS in phyllodes tumours is associated with malignancy, suggesting a possible role in malignant progression, particularly metastasising potential.

Adolescent↗