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Biomedical subjects

D Y Lee

Publications and source records attributed to D Y Lee.

At least 19 recordsLinked to original sources
PubMed2006

Amphiphilic triblock copolymer poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol), enhancement of gene expression and inhibition of lung metastasis by aerosol delivery.

We describe the development of an aerosol system for topical gene delivery to the lungs of C57BL/6 mice. This system is based on the combination of the commercial cationic lipid Lipofectin with a novel amphiphilic triblock copolymer, poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol) (PPDO/PLLA-b-PEG, and abbreviated in the text as polymeric micelles). After optimizing conditions for DNA delivery to the lungs of mice using the combination of polymeric micelles with Lipofectin and LacZ DNA, we used the Lipofectin/polymeric micelle system to deliver the tumor suppressor gene PTEN to the lungs of C57BL/6 mice bearing the B16-F10 melanoma. Lipofectin/PTEN/polymeric micelles significantly improved gene expression of PTEN in the lungs of mice with no evidence of cell toxicity or acute inflammation. Importantly, lung metastasis, as measured by lung weight, was significantly reduced (P<0.001), as were total tumor foci in the lungs (P<0.001) and size of individual tumor nodules in animals treated with Lipofectin/PTEN/polymeric micelles compared with control animals. Survival time was also extended. These results suggest that the Lipofectin/polymeric micelle system is appropriate for enhancing gene delivery in vivo and that it can be applied as a non-invasive gene therapy for lung cancer.

Aerosols↗
PubMed2006

Depression in vascular dementia is quantitatively and qualitatively different from depression in Alzheimer's disease.

BACKGROUND/AIMS: To compare the prevalence and characteristics of depression in vascular dementia (VaD) and Alzheimer's disease (AD) after adjusting for dementia severity and gender. METHODS: One hundred and eight pairs of VaD and AD patients matched for dementia severity and gender were assessed. RESULTS: Major depressive disorder (MDD) was more prevalent in the VaD group than in the AD group (20.4% in VaD, 10.2% in AD, p = 0.04, Cochran-Mantel-Haenszel, CMH, test) regardless of the dementia severity and gender. The odds ratio for developing MDD in the VaD group versus the AD group was estimated to be 2.20 (95% confidence interval = 1.02-4.74). Neurovegetative symptoms such as 'felt tired and weak all the time' (30.6% in VaD, 13.9% in AD, p = 0.003, CMH test) and 'changed weight without trying' (16.7% in VaD, 6.5% in AD, p = 0.02, CMH test) were more prevalent in the VaD group than in the AD group. CONCLUSION: Depression in VaD was quantitatively and qualitatively different from that in AD regardless of the severity of dementia and gender; depression was more prevalent, severer and more retarded and vegetative in VaD than in AD.

Aged↗
PubMed2006

Minimization of immunosuppressive therapy after islet transplantation: combined action of heme oxygenase-1 and PEGylation to islet.

We previously established a type of PEGylated islets to attenuate cellular immune reactions by immobilizing polyethylene glycol (PEG) molecules on islet surfaces, thereby synergistically reducing the dose of immunosuppressant cyclosporine A (CsA; 3 mg/kg/day) to protect transplanted islets. However, higher doses of immunosuppressants should be administered after islet transplantation due to nonspecific inflammation. This study documents that PEGylated islets can be cooperatively protected by the systemic overexpression of heme oxygenase-1 (HO-1), which has a potent cytoprotective function in preventing nonspecific inflammation during an early stage following islet transplantation. Under this scheme, the viability of PEGylated islets was improved; that is, PEG molecules could block cellular immunity and HO-1 could exert its cytoprotective property against inflammation. Interestingly, when employed with a low dose of CsA (1 mg/kg/day), a cooperative action of PEG molecules and HO-1 in immune reactions could result in the complete survival of transplanted islets for 100 days without islet function impairment. However, unmodified islets (control) were completely rejected within 2 weeks despite cotreatment with HO-1 expression and CsA. These results demonstrated that the combinatorial protocol of initial induction of HO-1 expression, followed by the daily administration of a low dose CsA after transplantation of PEGylated islets can be employed as a successful cell therapy in clinical islet transplantation.

Animals↗
PubMed2006

Tob is a potential marker gene for the basal layer of the epidermis and is stably expressed in human primary keratinocytes.

BACKGROUND: Epidermis consists of multiple layers, from the proliferating basal layer to terminal differentiated cornified layers, and these layers are defined by differentiation status. Tob gene product is known to be a member of the BTG antiproliferative protein family. We investigated the expression pattern of Tob gene product to understand the possible role in differentiation of keratinocytes and epidermis. OBJECTIVES: In this study, we examined the expression of Tob gene product in the primary cultured human keratinocytes and in the in vivo epidermis. METHODS: The expression of Tob gene product was assessed by Western blotting analysis. Cellular localization of Tob was detected using the green fluorescent protein-tagged Tob cDNA expression construct. In vivo expression of Tob gene product in the epidermis was determined by immunohistochemistry with paraffin sections. RESULTS: Tob family members are degraded by the ubiquitine-proteasome system triggered by the growth signal. Tob is stably and abundantly expressed in primary cultured human keratinocytes. Furthermore, the expression of Tob in the keratinocytes persists during the differentiation induced by calcium; however, it was not detected in primary cultured fibroblasts. Also, the subcellular localization of Tob is mainly in the cellular membrane in the primary human keratinocytes. We evaluated Tob expression in normal skin, oral mucosa and different diseases, such as psoriasis, X-linked ichthyosis and squamous cell carcinoma (SCC). Using immunohistochemical analysis, we observed that Tob was selectively expressed in the basal layer of X-linked ichythyosis and the hyperproliferative basal layer of psoriasis and oral mucosa as well as in normal epidermis. In SCC, the expression of Tob gene product was relatively decreased. CONCLUSIONS: Tob is stably expressed in primary human keratinocytes and it is specifically expressed in the basal layer of in vivo epidermis.

Blotting, Western↗
PubMed2006

The influence of facet tropism on herniation of the lumbar disc in adolescents and adults.

We carried out a study to determine the effect of facet tropism on the development of adolescent and adult herniation of the lumbar disc. We assessed 149 levels in 140 adolescents aged between 13 and 18 years and 119 levels in 111 adults aged between 40 and 49 years with herniation. The facet tropism of each patient was measured at the level of the herniated disc by CT. There was no significant difference in facet tropism between the herniated and the normal discs in both the adolescent and adult groups, except at the L4-L5 level in the adults. Facet tropism did not influence the development of herniation of the lumbar disc in either adolescents or adults.

Adolescent↗
PubMed2005

Neuroprotective role of microglia expressing interleukin-4.

Little is known about the underlying mechanisms responsible for the death of activated microglia and the functional consequences of the death of these cells, especially in vivo. We show here that intracortical injection of lipopolysaccharide (LPS) led to upregulation of interleukin-4 (IL-4) immunoreactivity, followed by a substantial loss of microglia 3 days later, as visualized by complement receptor type 3 (OX-42) immunostaining and tomato lectin staining. Cells positive for caspase-3 and terminal deoxynucleotidyl transferase mediated fluorescein-dUTP nick-end labeling (TUNEL) were also localized within LPS-activated microglia. IL-4 immunoreactivity was detected as early as 12 hr post-LPS, disappearing at 72 hr. Surprisingly, IL-4 immunoreactivity was detected exclusively in microglia, but not in astrocytes or neurons. In addition, IL-4-neutralizing antibodies markedly increased the survival of activated microglia at 3 days post-LPS. The expression of inducible nitric oxide synthase (iNOS) and tumor-necrosis factor (TNF)-alpha was sustained in parallel in activated microglia, consequently increasing neuronal cell death. To our knowledge, this study is the first to show the endogenous expression of IL-4 in LPS-activated microglia in vivo. Our findings suggest that IL-4 may regulate brain inflammation by inducing the death of activated microglia in vivo and increasing neuronal survival.

Analysis of Variance↗
PubMed2005

Diagnostic accuracy of mini-mental status examination and revised hasegawa dementia scale for Alzheimer's disease.

To compare the diagnostic accuracies of the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental Status Examination (MMSE) for Alzheimer's diseases (AD), we administered them simultaneously to 82 AD patients and 82 age- and sex-matched nondemented control subjects. The area under the receiver operator curve (AUC) for AD of the HDS-R (AUC(HDS-R)) and MMSE (AUC(MMSE)) were bigger than 0.90 indicating that both tests are useful for detecting AD. However, AUC(HDS-R) (0.952) was significantly larger than that of the AUC(MMSE )(0.902) regardless of the educational level of the subjects, indicating that the HDS-R is more accurate than MMSE in diagnosing AD. Moreover, the superiority of the HDS-R (AUC(HDS-R) = 0.894) to the MMSE (AUC(MMSE) = 0.704) remained significant in mild AD patients alone, who are the focus of screening. In conclusion, the HDS-R is better than the MMSE as a screening instrument for AD.

Aged↗
PubMed2005

A new drug carrier, Nalpha-deoxycholyl-L: -lysyl-methylester, for enhancing insulin absorption in the intestine.

AIMS/HYPOTHESIS: The development of an orally active insulin formulation will offer great advantages over conventional injectable insulin therapy in the treatment of patients with diabetes mellitus. Since insulin absorption in the intestine is restricted by the natural physiological characteristics of insulin, we developed a small synthetic compound, Nalpha-deoxycholyl-L: -lysyl-methylester (DCK), as an insulin carrier to enhance oral delivery. METHODS: Streptozotocin-induced diabetic rats orally received single doses of insulin (42 U/kg) or insulin/DCK formulation (10, 21, 30 and 42 U/kg) under fasting conditions. Blood glucose levels and plasma insulin concentrations were measured for 6 h following the administration of the agents. An OGTT was also performed immediately after the administration of the oral insulin/DCK formulation. RESULTS: The administration of 21, 30 and 42 U/kg (based on insulin activity) of insulin/DCK formulation reduced plasma glucose levels by up to 33.0% (median; range 30.6-70.2%), 78.5% (39.4-86.8%) and 75.2% (67.0-87.4%), respectively, compared with baseline levels. Furthermore, plasma insulin concentrations were observed to rapidly increase. In the OGTT, the insulin/DCK formulation reduced the AUC0-240 for glucose by 30.8% (22.3-54.9%) (p<0.01), and stabilized glycaemia for up to 4 h. CONCLUSIONS/INTERPRETATION: The results of this study demonstrate that the insulin/DCK formulation can be absorbed in the intestine and that it is biologically efficacious. We therefore suggest that this oral formulation could be used as an alternative to injectable insulin with enhanced clinical effects.

Animals↗
PubMed2004

The study on photoreflectance characteristic of semi-insulating GaAs surface region by its exposure to 6 MeV electron beam.

Photoreflectance measurements were performed to investigate the optical properties in the electron beam irradiation semi-insulating GaAs(e-beam irradiation GaAs) and semi-insulating GaAs(SI-GaAs). A considerable increase of the PR amplitudes has been registered after the e-beam irradiation in comparison with the GaAs. It is that result of a higher electron scattering on the lattice defects created by the e-beam.

Arsenicals↗
PubMed2004

Method for producing coded micro-carrier and test method by using a novel type biochip.

This paper provides a method for producing a novel type coded micro-carrier. A simple and cost effective solution for bio-molecule applications was developed. Application relevant items such as manufacture process, biospecific interaction, and analysis method are discussed. For low cost fabrication, the use of LIGA-like process is suggested. LIGA-like process is used as a dry patterning process in which an intense beam of light from an excimer laser is used to pattern a material directly. This process has found extensive application in the microelectronics industry for patterning of polymer materials. The use of LIGA-like techniques offers two attractive features: first, we can cut the polymer into many tiny micro-carriers with micrometer precision. Second, LIGA-like process allows to encode with high precision spatial information onto the micro-carrier that can be used in the identification of the bio-molecule. This paper gives a description of the basic idea, describes the fabrication of the novel micro-carrier that we called "coded micro-carrier," and of the image processing algorithms used for the analysis of bio-molecules. This study also provides a test method for identifying a bio-molecule, which includes mixing several coded micro-carriers with the hybridized unknown bio-molecules; and identifying the codes on the micro-carrier via image recognition system. The numbers and types of the known micro-carrier can be flexibly adjusted according to the number of tested bio-molecules.

Animals↗
PubMed2004

Uterine artery embolization for adenomyosis without fibroids.

AIM: To evaluate the potential usefulness of transcatheter uterine artery embolization as a treatment for symptomatic adenomyosis in patients without uterine fibroids. MATERIALS AND METHODS: Uterine artery embolization using polyvinyl alcohol particles sized 250-710 mm was performed in 43 patients (mean; 40.3 years, range; 31-52 years) with dysmenorrhoea, menorrhagia, or bulk-related symptoms (pelvic heaviness, urinary frequency) due to adenomyosis without fibroids. All patients underwent pre-procedural and 3.5 months (range 1-8 months) follow-up magnetic resonance imaging (MRI) with contrast enhancement. Clinical symptoms were also assessed at the time of MRI before and after embolization. RESULTS: Significant improvement of dysmenorrhoea (95.2%) and menorrhagia (95.0%) was reported in most patients. Contrast-enhanced MRI revealed non-enhancing areas suggesting coagulation necrosis of adenomyosis in 31 patients (72.1%), decreased size without necrosis in 11 patients (25.6%), and no change in one patient (2.3%). The mean volume reduction of the uteri after uterine artery embolization was 32.5% (from 321.7+/-142.9 to 216.7+/-130.1 cm(3)). CONCLUSION: Transcatheter uterine artery embolization is an effective therapy for the treatment of symptomatic pure adenomyosis, and may be a valuable alternative to hysterectomy.

Adult↗
PubMed2004

Quantitative analysis of interleukin-6 expression in porcine spleen cells and alveolar macrophages using real-time PCR.

Interleukin-6 (IL-6), a multifocal cytokine produced by lymphoid and non-lymphoid cells, regulates immune responses, acute-phase reactions against bacterial infections, and haematopoiesis. After cloning and sequencing of porcine IL-6, the expression pattern of porcine IL-6 mRNA was evaluated through real-time RT-PCR using porcine immune cells (spleen cells and alveolar macrophages) following stimulation with LPS. The sequence has been reported to GenBank with Accession no. AF 518322. The nucleotide sequence was different at the 89th and 205th positions in comparison with M80258, but only at the 205th with M86722. Comparison of porcine IL-6, Accession no. AF 518322, with IL-6 of human, canine, ovine, and mouse showed homologies of 78%, 81%, 82% and 73% in nucleotide sequence and 42%, 69%, 61% and 42% in amino acids. Expression of IL-6 mRNA was induced by stimulation with LPS. IL-6 mRNA expression in alveolar macrophages peaked at 2 h and decreased sharply to control levels at 4 h, whereas it peaked at 14 h and decreased at 24 h in spleen cells after stimulation with LPS (1 microg/ml). These results suggest that IL-6 mRNA expression in porcine immune cells is cell-type specific and the results of this study could be used as the basis for research on the porcine immune system.

Amino Acid Sequence↗
PubMed2004

Liquid chromatography-accurate radioisotope counting and microplate scintillation counter technologies in drug metabolism studies.

The present study involves an analysis of the performance of liquid chromatography (LC)-accurate radioisotope counting (ARC) and microplate scintillation counter (TopCount) technologies in drug metabolism studies. For the purpose of evaluating these systems, biological samples resulting from the metabolism of a radiolabeled [14C] compound, known as compound B, are analyzed using LC-ARC and TopCount under similar high-performance LC conditions. Counting efficiency is 83% for LC-ARC, 77% for TopCount, and linearity is R2 of 0.9998 versus 0.9984, respectively. The limit of detection for LC-ARC is 12 disintegrations per minute (dpm) with 1-min/fraction counting, yet for TopCount it is 8.7 dpm with 5-min/fraction counting. Under optimal conditions for each, the total run time of LC-ARC is approximately half that of TopCount. These results indicate that there is no significant difference between these two systems in terms of efficiency, linearity, and limit of detection. However, the LC-ARC system does not involve any manual operations, yet TopCount requires manual sample transfer and data import. This study shows that impressive progress has been made in the technology of radioisotope counting in drug metabolism using LC-ARC. This system enhances the resolution of radiochromatograms and is able to measure volatile metabolites that TopCount cannot detect at all. The ability to acquire mass spectra online is also a major advancement. The overall results suggest that the combination of LC-ARC with radioactivity detection and mass spectrometry has great potential as a powerful tool for radioisotope measurement in metabolite identification studies during drug discovery and development.

Chromatography, Liquid↗
PubMed2003

On-line liquid chromatography-accurate radioisotope counting coupled with a radioactivity detector and mass spectrometer for metabolite identification in drug discovery and development.

A novel detection method combining on-line liquid chromatography-accurate radioisotope counting (LC-ARC, advanced stop flow controller) coupled with a radioactivity detector and mass spectrometer has been developed. One of the major benefits of this method is that this system enhances the sensitivity of radioisotope measurement for metabolite identification in drug metabolism studies. Another advantage to this system is the easy interface with the mass spectrometer, which allows acquisition of mass spectrometric data on-line. For purposes of evaluating this system, in vitro microsomal incubations with [3Hlpropranolol were conducted. On-line separation and identification of [3H]propranolol metabolites was achieved without intensive sample preparation, concentration, or fraction collection. Mass spectrometric analysis showed the presence of propranolol major metabolites formed by hydroxylation, correlating with previously published results. Further evaluations of this system also were conducted using two 14C compounds, which are herein labeled X and Y. As our results show, 14C peaks were detected down to 6 cpm, which is approximately 20 times more sensitive than commercially available flow through radioactivity detectors. The overall results suggest that the combination of LC-ARC with radioactivity detection and mass spectrometry has great potential as a powerful tool for improving the sensitivity of radioisotope measurement in metabolite identification studies during drug discovery and development.

Animals↗
PubMed2002

Apolipoprotein E epsilon 4 allele is not associated with the cognitive impairment in community-dwelling normal elderly individuals.

OBJECTIVES: The aim of this study was to examine whether the APOE epsilon 4 allele also confers a risk for the cognitive impairment in normal aging. METHODS: We administered all the eight neuropsychological tests from the CERAD neuropsychological battery to the CVD-free, community-dwelling normal elderly individuals, and compared their performance by the occurrence of the APOE epsilon 4 allele. RESULTS: Either the impact of APOE epsilon 4 allele itself or its interaction terms with age and gender of the subjects did not influence the performance of the eight neuropsychological tests (epsilon p > 0.1 by ANCOVA). CONCLUSIONS: The APOE epsilon 4 allele is not a risk factor for the cognitive decline in normal elderly individuals regardless of age and gender.

Aged↗
PubMed2002

Development of the Korean version of Alzheimer's Disease Assessment Scale (ADAS-K).

OBJECTIVE: The purpose of this study was the development of the Korean Version of Alzheimer's Disease Assessment Scale (ADAS-K). METHOD: ADAS-K was administrated to 84 AD patients as well as 105 non-demented control subjects. Three aspects of reliability were tested. To evaluate the validity of ADAS-K, discriminant validity and concurrent validity were tested. To evaluate the sensitivity of ADAS-K to disease severity, all subjects, AD patients and control subjects, were grouped by CDR scale and their mean scores on ADAS-K were compared. RESULT: ADAS-K demonstrated high levels of reliability. Mean ADAS-K scores for AD patients were significantly different from the control group (p < 0.01). Furthermore, ADAS-K exhibited significant correlations with other tests and scales (range 0.45-0.85, p < 0.01). In ROC curve analysis, ADAS-K displayed high diagnostic efficacy and the optimal cut-off point was selected between 18/19. ADAS-K was able to discriminate the degree of AD severity according to CDR classification. Our results suggested that ADAS-K-cog was sensitive to very mild AD. CONCLUSION: We demonstrated that ADAS-K is a reliable and valid instrument not only for AD diagnosis but also for evaluation of its severity.

Aged↗
PubMed2002

The domain-specific, stage-limited impact of the apolipoprotein E epsilon-4 allele on cognitive functions in Alzheimer's disease.

To examine the impact of the APOE epsilon4 allele on the cognitive functions of Alzheimer's disease (AD) patients, we administered the eight neuropsychological tests from the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery to 118 Korean AD patients. The impact of the APOE epsilon4 allele was significant in the Word List Recall Test (WLRT) and the Word List Recognition Test (WLRcT) only, and its impact was confined to the very mild AD (VMAD) patients (F = 7.65, d.f. = 2, p < 0.01 for WLRT; F = 3.27, d.f. = 2, p = 0.04 for WLRcT). In the VMAD group, the performance on the two tests of the APOE-epsilon4-positive patients was poorer than that of the APOE-epsilon4-negative patients. Our findings suggest that the impact of the APOE epsilon4 allele on cognitive functions in AD may be domain specific and confined to the early stage of AD.

Aged↗