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Biomedical subjects

D H Lee

Publications and source records attributed to D H Lee.

At least 73 records · Page 4Linked to original sources
PubMed2001

Pharmacological properties of a newly synthesized H(+)/K(+) ATPase inhibitor, 1-(2-methyl-4-methoxyphenyl)-4-.

A new compound, 1-(2-methyl-4-methoxyphenyl)-4-[(3-hydroxypropyl)amino]-6-methyl-2,3-dihydropyrrolo[3,2-c]quinoline (DBM-819), given intraduodenally in pylorus-ligated rats, inhibited basal acid secretion with an ED(50) value of 3.5 mg/kg. In addition, DBM-819 reduced histamine- and pentagastrin-stimulated gastric acid secretion with ED(50) values of 4.0 and 5.1 mg/kg, respectively. The duration of the anti-secretory effect was approximately 18 h when DBM-819 was administered orally to rats with a chronic gastric fistula. Oral administration of DBM-819 protected against gastric lesions induced by ethanol, NaOH, indomethacin and aspirin, and the duodenal ulcer induced by cysteamine, in a dose-dependent manner with ED(50) values of 7.0, 20, 3.1, 4.0 and 6.0 mg/kg, respectively. Taken together, these results suggest that DBM-819 acts as an effective oral anti-ulcer agent in vivo, and that DBM-819 could be developed as a new therapeutic agent for peptic ulcer disease.

Animals↗
PubMed2001

Dose-dependent pharmacokinetics of a new reversible proton pump inhibitor, DBM-819, after intravenous and oral administration to rats: hepatic first-pass effect.

The dose-dependent pharmacokinetic parameters of DBM-819 were evaluated after intravenous (5, 10 and 20 mg/kg) and oral (10, 20 and 50 mg/kg) administrations of the drug to rats. The hepatic first-pass effect was also measured after intravenous and intraportal administrations of the drug, 10 mg/kg, to rats. After intravenous administration, the dose-normalized (based on 5 mg/kg) area under the plasma concentration-time curve from time zero to time infinity, AUC, at 20 mg/kg (27.0 and 45.8 microg min/ml) was significantly greater than that at 5 mg/kg due to saturable metabolism. After oral administration, the dose-normalized (based on 10 mg/kg) AUC(0-12 h) at 50 mg/kg (25.1, 18.3 and 49.2 microg min/ml) was significantly greater than those at 10 and 20 mg/kg again due to saturable metabolism. After oral administration of DBM-819, 10 mg/kg, 2.86% of oral dose was not absorbed and the extent of absolute oral bioavailability (F) was estimated to be 46.7%. After intraportal administration of DBM-819, 10 mg/kg, the AUC was 51.9% of intravenous administration, suggesting that approximately 48.1% was eliminated by liver (hepatic first-pass effect). The considerable hepatic first-pass effect of DBM-819 was also supported by significantly greater AUC of M3 (3.70 and 6.86 microg min/ml), a metabolite of DBM-819, after intraportal administration. The AUCs of DBM-819 were not significantly different (comparable) between intraportal and oral administrations of the drug, 10 mg/kg, suggesting that gastrointestinal first-pass effect of DBM-819 was almost negligible in rats. At 10 mg/kg oral dose of DBM-819, the hepatic first-pass effect was approximately 48.1%, F was approximately 46.7 and 2.86% was not absorbed from gastrointestinal tract in rats.

Administration, Oral↗
PubMed2001

In vitro metabolism of a new H(+)/K(+) ATPase inhibitor DBM-819 in liver microsomes using HPLC and electrospray mass spectrometry.

The metabolism of 1-(2-methyl-4-methoxyphenyl)-4-[(3-hydroxypropyl)amino]-6-methyl-2,3-dihydropyrrolo[3,2c]quinoline (DBM-819), a new H(+)/K(+) ATPase inhibitor, has been studied by HPLC with spectrometric detection and on-line LC-electrospray mass spectrometry. In vitro incubation of DBM-819 with rat liver microsomes in the presence of NADPH resulted in the production of four metabolites (M1-4), whereas DBM-819 was oxidized to two metabolites, M2 and M4, by human liver microsomes. M2, M3 and M4 were identified as O-demethyl-DBM-819, 8-hydroxy-DBM-819 and N-dehydroxypropyl-DBM-819, respectively, based on LC/MS/MS analysis with authentic standards. M1 was tentatively identified as 1-(hydroxy-2-methyl-4-methoxyphenyl)-4-[(3-hydroxypropyl)amino]-6-methyl-2,3-dihydropyrrolo[3,2c]quinoline. Rat liver CYP1A1/2 catalyzed the oxidation of DBM-819 to 8-hydroxy-DBM-819 and N-dehydroxypropyl-DBM-819. Human CYP3A4 was a major isozyme for the formation of O-demethyl-DBM-819 as well as N-dehydroxypropyl-DBM-819.

Animals↗
PubMed2001

Systematic methodology for the design of a flexible keel for energy-storing prosthetic feet.

An effective design method is suggested for a flexible keel design for energy-storing prosthetic feet (ESPF). The basic, two-dimensional shape of the keel is based on anthropometric data and normal gait analysis available in the literature. Cost function is defined for the performance evaluation of the keel. Five factors and five levels of their effect on the performance of the keel are established. By use of an orthogonal array table, 25 trials of dynamic simulations of prosthetic walking are designed, from among 3,125 possible combinations, dramatically reducing the number of total simulations needed to examine sufficiently the contribution of each factor to cost function. A prosthetic walking model is built, and a dynamic simulation of prosthetic walking is performed using the finite element method. The contribution of each factor to cost function is investigated by an analysis of variance (ANOVA), and the average main effects of factors for cost function are calculated. The optimum combination of factor levels is obtained by minimisation of cost function. To examine the structural safety of the keel, the deformation and stress distribution of the keel are investigated by static analysis, and failure indices are calculated by three failure criteria. Finally, the optimum flexible keel is designed with increased energy storage capacity, without failure, and suitable for more active prosthetic walking; the recoverable strain energy stored in the optimum ESPF keel is 25.8J.

Analysis of Variance↗
PubMed2001

Studies on the possible mechanisms of protective activity against alpha-amanitin poisoning by aucubin.

Aucubin, an iridoid glucoside, was investigated to determine whether it has a stimulating effect on alpha-amanitin excretion in alpha-amanitin intoxicated rats, and whether there is binding activity to calf thymus DNA. High-performance liquid chromatography (HPLC) analysis of alpha-amanitin in rat urine allowed quantitative measurement of the alpha-amanitin concentration with a detection limit of 50 ng/ml. In this system, a group treated with both alpha-amanitin and aucubin showed that alpha-amanitin was excreted about 1.4 times faster than in the alpha-amanitin only treated group. Our previous results showed that the toxicity of alpha-amanitin is due to specific inhibition of RNA polymerase activity and the resultant blockage of the synthesis of certain RNA species in the nucleus. However, no significant activity change on RNA polymerase from Hep G2 cells was observed when aucubin was treated with alpha-amanitin at any concentration tested. Nevertheless, aucubigenin inhibited both DNA polymerase (IC50, 80.5 microg/ml) and RNA polymerase (IC50, 135.0 microg/ml) from the Hep G2 cells. The potential of both alpha-amanitin and aucubin to interact with DNA were examined by spectrophotometric analysis. Alpha-Amanitin showed no significant binding capacity to calf thymus DNA, but aucubin was found to interact with DNA, and the apparent binding constant (Kapp) and apparent number of binding sites per DNA phosphate (Bapp) were 0.45 x 10(4) M(-1) and 1.25, respectively.

Amanitins↗
PubMed2001

Monitoring cerebral perfusion after subarachnoid hemorrhage using CT.

The aim of this prospective study was to assess the feasibility and diagnostic relevance of repetitive dynamic (contrast-enhanced) CT measurements of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in the first 3 weeks after aneurysmal subarachnoid hemorrhage (SAH). In 15 patients with SAH, 59 dynamic CT studies including 944 regions of interest (ROI) were analyzed. The results were correlated with the clinical course and time after the event and the occurrence of vasospasm. Values for the entire series were 33.8+/-19.3 ml/100 g/min (CBF), 3.3+/-1.3 ml/100 g (CBV), and 7.3+/-3.9 s (MTT). Significant differences in CBF and CBV were found between ROI in grey and white matter, with time after the event, between patients with significant and absent or minor vasospasm, and between patients with and without a presumed vasospasm-related infarct.

Cerebrovascular Circulation↗
PubMed2001

Mutations at the APC exon 15 in the colorectal neoplastic tissues of serial array.

Although the APC protein is known to participate in cellular proliferation and apoptosis, APC mutations have been thought to play a major role in the early stage of colorectal tumorigenesis. The somatic APC mutation of exon 15 was assessed to determine its impact on various stages of colorectal tumorigenesis. The colorectal neoplastic tissues of serial array studied included sporadic adenomas (group 1, n = 36), adenomas (group 2, n = 33), and carcinomas (group 3, n = 32) in the synchronous adenoma and carcinoma as well as sporadic carcinomas (group 4, n = 36). Aberrant DNA was detected by protein truncation test and confirmed by direct sequencing. The mutation prevalence was 36.1% in group 1, 45.5% in group 2, 59.4% in group 3, and 41.7% in group 4 with no differences among the groups. Among the 18 patients with synchronous adenoma and carcinoma, 9 had mutation in their adenomas and 12 in their carcinomas. The mutation loci and patterns did not differ in adenomas and carcinomas. Mutations in the mutation cluster region (MCR) were much more frequent than in the preceding region of MCR, i.e., 85.7% vs. 14.3%. The mutation prevalence of villous adenomas appeared greater than that of tubular adenoma (3/21 vs. 3/4). Predominant pathogenic mutations at MCR suggest that the APC mutation is implicated in all stages of colorectal tumorigenesis.

Adenocarcinoma↗
PubMed2001

Treatment options for complex elbow fracture dislocations.

The management of complex elbow fractures and fracture-dislocations requires an accurate assessment of the patterns of elbow injury. The surgical management of these injuries, in order to restore elbow stability and function, includes reconstruction of the articular surfaces and stabilization of the periarticular soft tissues. A surgical algorithm is presented to provide guidelines for treating these complex injuries.

Algorithms↗
PubMed2001

Molecular cloning and characterization of a mu-class glutathione S-transferase from Clonorchis sinensis.

In biliary passages, Clonorchis sinensis causes epithelial hyperplasia and is assumed to promote carcinogenesis. Glutathione S-transferase (GST) is an antioxidant enzyme involved in phase II defense in trematodes. A clone (pcsGSTM1) encoding a GST was identified by screening a C. sinensis cDNA library with a PCR-synthesized cDNA probe. The predicted amino acid sequence encoded by pcsGSTM1 cDNA had a high degree of sequence identity and folding topology similar to the mu-class GSTs. The estimated molecular mass of the protein, 26 kDa, was consistent with an expression by pcsGSTM1 cDNA. The bacterially expressed recombinant csGSTM1 protein possessed an enzymatic GST activity and conjugated GSH to reactive carbonyls of lipid peroxidation. The recombinant csGSTM1 protein did not share antigenic epitope(s) with GSTs of Fasciola hepatica, Paragonimus westermani and Schistosoma japonicum. The csGSTM1 was identified to a mu-class GST in C. sinensis.

Amino Acid Sequence↗
PubMed2001

Effect of a capsular tension ring on the shape of the capsular bag and opening and the intraocular lens.

PURPOSE: To evaluate the effect of a capsular tension ring (CTR) on the shape of the capsular bag, the extent of the capsular opening, and the shape of intraocular lenses (IOLs). SETTING: Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Korea. METHODS: The corneal button was removed from porcine eyes in vitro. After phacoemulsification was performed, an IOL alone or an IOL and CTR were inserted in the capsular bag in 6 groups of 5 eyes each. The eyes were examined from the posterior aspect using a Miyake technique to assess capsular bag shape and the capsular opening. To evaluate effects of the CTR on IOL shape, rabbit eyes had phacoemulsification and IOL implantation with and without placement of a CTR in vivo. The IOLs were removed from enucleated eyes 3 months postoperatively and compared with unused control IOLs. RESULTS: The differences between the maximum and minimum diameters of the capsular bags and capsular openings were significantly less in groups with a CTR. Intraocular lens size (difference from haptic to haptic) decreased significantly in eyes with only an IOL compared with normal controls or eyes with both an IOL and CTR. CONCLUSIONS: The CTR preserved the integrity of the capsular bag diameter, capsular opening, and IOL shape. It is likely that CTR implantation can avert contracture of the capsular bag and capsular opening, preventing IOL decentration.

Animals↗
PubMed2001

Covered retrievable tracheobronchial hinged stent: an experimental study in dogs.

PURPOSE: To evaluate the safety and technical feasibility of the use of a covered retrievable tracheobronchial hinged stent and investigate the histopathologic airway changes after placement and removal of the stent in dogs. MATERIALS AND METHODS: The experimental stent was composed of tracheal and bronchial stents that were connected together at their ends. Each stent was woven from a single thread of 0.2-mm-diameter nitinol wire filament in a tubular configuration and covered with polyurethane solution by a dipping method. Drawstrings were attached at the upper end of the tracheal stent for stent removal. Under fluoroscopic guidance, 20 stents were placed at the lower trachea and left main bronchus in 20 dogs and were electively removed 4 weeks (n = 10) or 8 weeks (n = 10) after placement. Ten dogs were killed just after stent removal and the remaining 10 were killed 2 weeks after stent removal. RESULT: Stents were successfully placed in all dogs. Pneumonia was observed in three dogs. Stent migration occurred in seven dogs (35%). Except for two cases of stent expectoration, 18 stents were easily removed within a few minutes. There was considerable granulation tissue proliferation and inflammatory reaction in the airways of the dogs that were killed just after stent removal. The pathologic changes of the airways returned to almost-normal conditions 2 weeks after stent removal. CONCLUSION: Placement and removal of a covered retrievable tracheobronchial hinged stent seems to be feasible, and histopathologic changes of the airway related to the stents returned to normal 2 weeks after stent removal.

Animals↗
PubMed2001

Balloon dacryocystoplasty: results and factors influencing outcome in 350 patients.

PURPOSE: To evaluate the initial and long-term results of balloon dacryocystoplasty in the treatment of epiphora caused by obstruction of the lacrimal system with analysis of the procedure's favorable effects. MATERIALS AND METHODS: Four hundred thirty eyes of 350 patients with obstructions of the lacrimal system were enrolled. Dacryocystoplasty was performed with use of a balloon catheter and a ball-tipped guide wire. The lesions were categorized according to cause, severity, site of the obstruction, and diameter and inflation time of the balloon. The technical success, initial success (improvement of symptoms after 1 week), and long-term patency rates were calculated. These rates in each group were compared with the chi(2) test and the Kaplan-Meier method. RESULTS: The overall technical success rate was 95.3%. The overall initial success rate was 57.4%. There was no significant complication except for mild epistaxis in 12%. The 2-month, 1-year, and 5-year patency rates were 48.2%, 39.4%, and 36.9%, respectively. Initial success was influenced by the severity (P =.014) and the site (P <.001) of the obstruction, and the diameter of the balloon (P =.047). Long-term patency was affected by the site of the obstruction (P <.001) and the balloon inflation time (P <.001). Among the 183 initially ineffective and 88 recurrent cases, 62 underwent repeat balloon dacryocystoplasty, and the initial success rate was 38.7%. CONCLUSIONS: The initial success rate of balloon dacryocystoplasty is relatively low. However, long-term patency can be expected in cases with initial success. Some additional factors also should be considered for better results.

Adolescent↗
PubMed2001

Data mining approach to policy analysis in a health insurance domain.

This study examined the characteristics of the knowledge discovery and data mining algorithms to demonstrate how they can be used to predict health outcomes and provide policy information for hypertension management using the Korea Medical Insurance Corporation database. Specifically, this study validated the predictive power of data mining algorithms by comparing the performance of logistic regression and two decision tree algorithms, CHIAD (Chi-squared Automatic Interaction Detection) and C5.0 (a variant of C4.5) using the test set of 4588 beneficiaries and the training set of 13,689 beneficiaries. Contrary to the previous study, the CHIAD algorithm performed better than the logistic regression in predicting hypertension, and C5.0 had the lowest predictive power. In addition, the CHIAD algorithm and the association rule also provided the segment-specific information for the risk factors and target group that may be used in a policy analysis for hypertension management.

Algorithms↗
PubMed2001

Intranet-based quality improvement documentation at the Veterans Affairs Maryland Health Care System.

The Pathology and Laboratory Medicine Service of the Veterans Affairs Maryland Health Care System is inspected biannually by the College of American Pathologists (CAP). As of the year 2000, all documentation in the Anatomic Pathology Section is available to all staff through the VA Intranet. Signed, supporting paper documents are on file in the office of the department chair. For the year 2000 CAP inspection, inspectors conducted their document review by use of these Web-based documents, in which each CAP question had a hyperlink to the corresponding section of the procedure manual. Thus inspectors were able to locate the documents relevant to each question quickly and efficiently. The procedure manuals consist of 87 procedures for surgical pathology, 52 procedures for cytopathology, and 25 procedures for autopsy pathology. Each CAP question requiring documentation had from one to three hyperlinks to the corresponding section of the procedure manual. Intranet documentation allows for easier sharing among decentralized institutions and for centralized updates of the laboratory documentation. These documents can be upgraded to allow for multimedia presentations, including text search for key words, hyperlinks to other documents, and images, audio, and video. Use of Web-based documents can improve the efficiency of the inspection process.

Databases, Factual↗
PubMed2001

Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer's disease.

AIMS: Amyloid has recently been shown to accumulate intracellularly in the brains of patients with Alzheimer's disease (AD), yet amyloid plaques are generally thought to arise from gradual extracellular amyloid deposition. We have investigated the possibility of a link between these two apparently conflicting observations. METHODS AND RESULTS: Immunohistochemistry and digital image analysis was used to examine the detailed localization of beta-amyloid(42) (A beta 42), a major component of amyloid plaques, in the entorhinal cortex and hippocampus of AD brains. A beta 42 first selectively accumulates in the perikaryon of pyramidal cells as discrete, granules that appear to be cathepsin D-positive, suggesting that they may represent lysosomes or lysosome-derived structures. AD brain regions abundantly populated with pyramidal neurones exhibiting excessive A beta 42 accumulations also contained evidence of neuronal lysis. Lysis of these A beta 42-burdened neurones apparently resulted in a local, radial dispersion of their cytoplasmic contents, including A beta 42 and lysosomal enzymes, into the surrounding extracellular space. A nuclear remnant was found at the dense core of many amyloid plaques, strengthening the idea that each amyloid plaque represents the end product of a single neuronal cell lysis. The inverse relationship between the amyloid plaque density and pyramidal cell density in the AD brain regions also supports this possibility, as does the close correlation between plaque size and the size of local pyramidal cells. CONCLUSIONS: Our findings suggest that excessive intracellular accumulation of A beta 42-positive material in pyramidal cells can result in cell lysis, and that cell lysis is an important source of amyloid plaques and neuronal loss in AD brains.

Aged↗
PubMed2001

A bone replaceable artificial bone substitute: cytotoxicity, cell adhesion, proliferation, and alkaline phosphatase activity.

Cellular toxicity, cell adhesion and proliferation, and alkaline phosphatase (ALP) activity were investigated for an artificial bone substitute composed of heated carbonate apatite (CAp) and Type I atelocollagen (AtCol) extracted from bovine tail skins (88/12 in %wt/wt). To enhance the intramolecular crosslinking between collagen molecules, the CAp-AtCol substitutes were irradiated by ultraviolet rays (wave length 254 nm) at 4 degrees C for 4 h or vacuum dried at 150 degrees C for 2 h. Cytotoxicity tests by a direct contact method and an extract dilution method revealed that the CAp-AtCol substitutes were cytocompatible for balb 3T3 fibroblasts. Osteoblast adhesion studies demonstrated that the substitute disks composed of 980 degrees C-heated CAp and AtCol were significantly more adhesive for osteoblasts than those of 1,200 degrees C-sintered CAp and AtCol (p < 0.05). Proliferation studies showed that the number of osteoblasts grown in the media containing substitutes of 980 degrees C-heated CAp and AtCol was statistically higher than grown in those of 1,200 degrees C-sintered CAp and AtCol after 5 days (p < 0.05). It was found that osteoblasts grown in the substitutes of 980 degrees C-heated CAp and AtCol only expressed similar ALP activity to the controls. These results suggested that the substitutes consisting of 980 degrees C-heated CAp and AtCol show more favorable interactions with osteoblasts than those of 1,200 degrees C-sintered CAp and AtCol.

3T3 Cells↗
PubMed2001

A bone replaceable artificial bone substitute: osteoinduction by combining with bone inducing agent.

Bone inducing agent (BIA) isolated from Saos-2 human osteosarcoma cells was added to an artificial bone substitute composed of 980 degrees C-heated carbonate apatite (CAp) and Type I atelocollagen (AtCol) extracted from bovine tail skins (88/12 in wt/wt %), and a CAp-AtCol-BIA substitute was prepared as an osteoinductive bone substitute. Rat calvaria osteoblasts treated by the isolated BIA demonstrated significantly increased alkaline phosphatase (ALP) activity after 3 days (p < 0.05). In vitro cell attachment and proliferation and ALP activity were investigated for the bone substitute combined with BIA. Osteoblasts cultured onto the surface of the CAp-AtCol-BIA substitute demonstrated remarkable morphological changes such as radial spreading, flattening, and projecting filopodia after 5 days. In comparison with the substitute without BIA, osteoblasts grown in the BIA-combined CAp-AtCol substitute expressed significantly increased proliferation and ALP activity, respectively (p < 0.05). Both the substitutes combined with and without BIA were implanted into artificial defects created in rabbit radii. After 4 weeks, the CAp-AtCol-BIA substitute implanted lesion was completely replaced by regenerated host bone in radiological observation whereas the substitute without BIA was partially resorbed. No histologic abnormalities appeared in the substitute either with or without BIA.

Alkaline Phosphatase↗