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Biomedical subjects

H B Lee

Publications and source records attributed to H B Lee.

At least 37 records · Page 2Linked to original sources

Serum levels of interleukins (IL)-4, IL-5, IL-13, and interferon-gamma in acute asthma.

T-cell activation and alteration of cytokine levels are involved in the pathogenesis of bronchial asthma. However, the profile of circulating T-lymphocyte subsets and related cytokines during acute asthmatic attacks is still unclear. We hypothesized that serum levels of interleukin (IL)-4, IL-5, and IL-13 would be increased, whereas IFN-y would be decreased in acute asthma. The subjects enrolled in this study included 58 acute asthmatics, 22 asymptomatic asthmatics, and 10 healthy controls. Serum levels of IL-4, IL-5, IL-13, and IFN-gamma were measured using a sandwich enzyme-linked immunosorbent assay. We correlated serum levels of IL-4, IL-5, IL-13, and IFN-gamma with initial forced expiratory volume in 1 sec (FEV1). Compared with control subjects, acute asthmatics had significantly increased levels of circulating IL-4 (p < 0.001), IL-5 (p < 0.001), and IL-13 (p < 0.001), although the differences were of borderline significance in serum IFN-gamma (p = 0.069). There were also significant differences in the circulating levels of IL-4, IL-5, and IL-13 between acute asthmatics and asymptomatic asthmatics. There was no significant association between initial FEV1 and serum levels of IL-4 or IL-13, however, among acute asthmatics, a lower initial FEV1 was associated with higher IL-5 and/or lower IFN-gamma levels. Our results suggest that serum levels of IL-4, IL-5, and IL-13 may be elevated in acute asthma, and that higher levels of IL-5 and/or lower levels of IFN-gamma are associated with severe airway obstruction.

Acute Disease↗

A short sequence within domain C of duck carboxypeptidase D is critical for duck hepatitis B virus binding and determines host specificity.

Virus-cell surface receptor interactions are of major interest. Hepadnaviruses are a family of partially double-stranded DNA viruses with liver tropism and a narrow host range of susceptibility to infection. At least in the case of duck hepatitis B virus (DHBV), host specificity seems controlled partly at the receptor level. The middle portion in the pre-S region of the viral large envelope protein binds specifically to duck carboxypeptidase D (DCPD) but not to its human or chicken homologue. Although domain C of DCPD is implicated in ligand binding, the exact pre-S contact site remains to be determined. We prepared and tested a panel of chimeric constructs consisting of DCPD and human carboxypeptidase D (HCPD). Our results indicate that a short region at the N terminus of domain C (residues 920 to 949) is critical to DHBV binding and is a major determinant for the host specificity of DHBV infection. Replacing this region of the DCPD molecule with its human homologue abolished the DHBV interaction, whereas introducing this DCPD sequence into HCPD conferred efficient DHBV binding. Extensive analysis of site-directed mutants revealed that both conserved and nonconserved residues were important for the pre-S interaction. There were primary sequence variations and secondary structural differences that contributed to the inability of HCPD to bind the DHBV pre-S domain.

Amino Acid Sequence↗

Prevalences of symptoms of asthma and other allergic diseases in korean children: a nationwide questionnaire survey.

The purpose of this study was to estimate the national prevalence of childhood asthma and other allergic diseases in Korea, and to determine potential risk factors for the diseases. Stratified random samples of 42,886 were selected from 34 elementary (6-12 yr olds) and 34 middle schools (12-15 yr olds) nationwide, and 38,955 were in the final analysis. The Korean-translated modified version of the International Study of Asthma and Allergies in Childhood questionnaire was used in this cross-sectional survey. Twelve-month prevalences of the symptoms of asthma, rhinoconjunctivitis, and flexural eczema were 8.7%, 10.5%, 7.3% in 6-12 yr olds, and 8.2%, 10.0%, 3.9% in 12-15 yr olds, respectively. For allergic conjunctivitis, food allergy, and drug allergy, the prevalences in 6-12 yr olds were 11.2%, 6.5%, and 1.5%, respectively. Asthma and flexural eczema decreased significantly with age. Other significant risk factors were also noted. For 6-12 yr-old asthma, adjusted odds ratio (aOR) of body mass index was 1.21 with 95% confidence interval (CI) 1.0-1.48, aOR of passive smoking was 1.37 with 95%CI 1.24-1.51, aOR of carpet use was 1.28 with 95%CI 1.10-1.49. For 6-12 yr-old eczema, aOR of affluence was 1.22 with 95%CI 1.07-1.39. The control of obesity and passive smoking would be the most important preventive measures of allergic diseases.

Adolescent↗

Comparison of bone morphogenetic protein receptors expression in the fetal and adult skin.

Wounds on fetal skin can be repaired without leaving scars until the second trimester, but after this period, skin wounds leave scars as in adults. It's known that certain growth factors such as TGF-beta, and bFGF are present at a very low levels during wound repair in fetal skin. These low levels of growth factors minimize inflammatory response and fibroblast proliferation at the wound site, which in turn inhibit collagen synthesis, and thus, allows scarless wound healing. Recently bone morphogenetic proteins (BMPs), one of the TGF-beta superfamily members, have been studied in the wound healing process. According to several studies, BMPs are related to the differentiation and growth of epithelial and mesenchymal cells, but the precise functions of BMPs and of BMP receptors on skin wound healing have not been elucidated. In this study, we investigated the expression pattern of BMP receptors in fetal skin during the second trimester and in adult skin by immunohistochemical staining and RT-PCR. BMP receptors were detected on the suprabasal epithelial cells and in the hair follicles in adult skin, but were not defected in the fetal skin except for the hair follicles. This was confirmed by confirming mRNA levels of BMP receptors by RT-PCR in both adult and fetal skins. In conclusion, BMPs and BMP receptors seem to be related to fetal and adult wound healing, and low levels of BMPs and BMP receptors during the second trimester seem to contribute to scarless wound healing in the fetus, as is TGF-beta during the second trimester.

Bone Morphogenetic Protein Receptors↗

Intrathoracic malignant peripheral nerve sheath tumor in von Recklinghausen's disease.

Malignant peripheral nerve sheath tumor (MPNST) is defined as any malignant tumor arising from or differentiating toward the cells of the peripheral nerve sheath. MPNST accounts for about 5-10% of all soft tissue tumors and is often associated with neurofibromatosis type I (NF-1, von Recklinghausen's disease). It is one of the malignant tumors associated with von Recklinghausen's disease. Its common site is the lower and upper extremities, trunk, head and neck. But intrathoracic manifestations are very rare. We report a case of a 40 year-old man with multiple neurofibromatosis who was presented with an intrathoracic malignant peripheral nerve sheath tumor.

Adult↗

In vivo detection of deposition of radiolabeled lupus antikidney antibody and its inhibition by soluble antigen.

UNLABELLED: This investigation in an animal model was designed to test the feasibility of using radiolabeled lupus antikidney antibody to show renal deposition in vivo and the ability to block this deposition with a binding peptide. METHODS: BALB/c mice received injections of radiolabeled murine anti-DNA antibody, antibody with no DNA binding capability, and DNA antibody simultaneously with blocking peptide. RESULTS: Significantly higher renal deposition of anti-DNA antibody than of antibody without DNA binding capability occurred in the animals at 48 h after injection (5.21% of the injected dose per gram of tissue versus 2.5%, P < 0.0004) and at 7-8 d after injection (1.44% versus 0.20%, P < 0.00004). The simultaneous injection of blocking peptide with anti-DNA binding antibody significantly reduced the renal deposition of the anti-DNA antibody at 48 h (1.53%, P < 0.00001) and at 7-8 d (0.64%, P < 0.0017). CONCLUSION: This study showed the feasibility of using a radiolabeled antibody to evaluate deposition of anti-DNA antibody in the kidney and the successful use of a peptide to block antibody deposition-a strategy that may be useful for renal preservation in lupus. These data support the possibility of using antikidney-labeled antibodies to evaluate immunologic renal disease in vivo in humans.

Animals↗

Preparation and characterization of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) microspheres for the sustained release of 5-fluorouracil.

Biodegradable microspheres were prepared with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV, 85:15 by mole ratio of hydroxybutyrate to hydroxyvalerate) by an water-in-oil-in-water (W/O/W), oil-in-water (O/W) and oil-in-oil (O/O) solvent evaporation method for the sustained release of anti-cancer drug, 5-fluorouracil (5-FU) with controlling the fabrication conditions. The shape of microspheres prepared was relatively rough due to highly crystalline property of PHBV and spherical. The efficiency of 5-FU loading into the PHBV microsphere with O/O method was over 80% compared to that 7% for microspheres by O/W method and below 1% for microspheres by a conventional W/O/W method. However, the most desirable release pattern can be achieved from the O/W method due to the cosolvent effect. The effects of preparation conditions such as the type and amount of surfactant, initial amount of loaded drug, the temperature of solvent evaporation, and etc. on the morphology for W/O/W method were investigated. Possible mechanisms of the desirable sustained release pattern for O/W system have been proposed.

Antineoplastic Agents↗

A case of bronchiolitis obliterans organizing pneumonia with renal dysfunction after renal transplantation.

A 35-year-old male renal transplant patient was admitted with 3-week history of cough and myalgia after a 3-month post-transplantation. The patient's posttransplant course was uncomplicated and had no rejection. But on admission, the serum creatinine was 3.0 mg/dl and high-resolution computed tomography (HRCT) showed bilateral patchy densities and peripheral consolidations. Renal biopsy revealed mononuclear cell infiltration and non-specific tubular injury without evidence of rejection. An open lung biopsy was performed which showed multiple fibroblast plugs filling airspaces that were typical pathologic features of bronchiolitis obliterans with organizing pneumonia (BOOP). After prednisone therapy, the patient's pulmonary symptoms and radiographic findings rapidly recovered and serum creatinine also decreased from 3.0 to 2.1 mg/dl. Although the cause of renal dysfunction was not elucidated, we herein report a rare case of BOOP with renal dysfunction after renal transplantation.

Adult↗

Characterization of compression-molded UHMWPE, PMMA and PMMA/MMA treated UHMWPE: density measurement, FTIR-ATR, and DSC.

Considered one of the weak links in the total hip replacement (THR), efforts to enhance the interfacial strength between bone cement and ultra-high molecular weight polyethylene (UHMWPE) acetabular cup had been conducted in this laboratory. Following the successful demonstration of high interfacial strengths for our new acetabular component design, the nature of physical, chemical, and thermal property of the compression-molded specimens, including UHMWPE, PMMA/MMA treated UHMWPE, and PMMA has been investigated in this study. Density results from a density gradient column showed that the molding processes and conditions were adequate for complete sintering of UHMWPE and PMMA powders. FTIR-ATR results gave a direct evidence that PMMA did exist in the PMMA/MMA treated UHMWPE matrix. It also revealed a clear diffusion-related behavior across the interface. Under the high temperature and pressure, the UHMWPE powders undergo drastic changes of their morphology and crystalline structures. These changes were examined by differential scanning calorimeter (DSC) which showed a large difference in terms of % crystallinity. The percent of PMMA deposited in the treated UHMWPE was 17.8%, 18.8%, and 24.3% from the analyses of density, FTIR-ATR, and DSC, respectively. Finally, an evidence of diffusive behavior at the interface exhibited diffusion of PMMA occurring across the interfaces between the treated UHMWPE and UHMWPE or PMMA.

Bone Cements↗

Impact of environment and interspecific interactions between spoilage fungi and Aspergillus ochraceus on growth and ochratoxin production in maize grain.

Using layers of irradiated but still fertile maize grain, the effects of water activity (0.995, 0.95 a(w)) and temperature (18, 30 degrees C) on interspecific interactions between Aspergillus ochraceus and five other spoilage fungi were examined. Asp. ochraceus was not competitive against Asp. flavus, Asp. niger, or Alternaria alternata at 18 degrees C when water was freely available (0.995 a(w)), while at 0.95 a(w) it was dominant against Asp. candidus, Asp. flavus and Alt. alternata. At 30 degrees C and 0.995 a(w), Asp. ochraceus was dominated by other fungi, except Alt. alternata, and was mutually antagonistic to Asp. candidus and Eurotium amstelodami. However, at 30 degreees C and 0.95 a(w), it was competitive against Asp. candidus and Alt. alternata, but not against the other species examined. The overall Index of Dominance showed that Asp. ochraceus was not competitive under the conditions examined here. At 18 degrees C ochratoxin production by Asp. ochraceus was inhibited significantly by Asp. candidus (0.995 and 0.95 a(w)) and Asp. niger (0.995 a(w)). When grown on maize grain at 30 degrees C, ochratoxin production by Asp. ochraceus was significantly inhibited by other spoilage fungi when both were grown on maize grain, especially by Asp. niger and E. amstelodami (0.995 a(w)) and Asp. flavus at 0.95 a(w). These results suggest that, to a large extent, A. ochraceus is not as competitive as some other spoilage fungi in primary resource capture on maize grain at a(w) of 0.95 or above, although it may modify resource quality and influence secondary colonisation by other species under the conditions tested.

Alternaria↗

Nifedipine controlled delivery by sandwiched osmotic tablet system.

The sandwiched osmotic tablet system (SOTS), which is composed of a sandwiched osmotic tablet core surrounded by a cellulose acetate membrane with two orifices on both side surfaces, has been successfully prepared with the purpose of delivering nifedipine. The sandwiched osmotic tablet core consists of a middle push layer and two attached drug layers. Influences of tablet formulation variables, orifice size and membrane variables on nifedipine release of SOTS have been studied. It was found that potassium chloride amount of push layer and polyethylene oxide amount of drug layer had markedly positive effects on nifedipine release. A push layer/drug layer co-controlled osmotic delivery mechanism and the optimal core formulation have been proposed. The appropriate orifice size was observed in the range of 0.50-1.41 mm. It was also found that the drug release rate of SOTS could be increased by incorporating hydrophilic plasticizer in the membrane, whereas it decreased with hydrophobic plasticizer. It has been observed that the SOTS gives fairly comparable in vitro release features as that of commercialized push-pull osmotic tablet system, such as an approximately constant rate up to 24 h and independence of release media and agitation rate. Exempting side identification before drilling, it is easier to prepare the SOTS than the push-pull osmotic tablet system.

Calcium Channel Blockers↗

Monolithic osmotic tablet system for nifedipine delivery.

The monolithic osmotic tablet system, which is composed of a monolithic tablet coated with cellulose acetate (CA) membrane drilled with two orifices on both side surfaces, has been described. The influences of tablet formulation variables including molecular weight (MW) and amount of polyethylene oxide (PEO), amount of potassium chloride (KCl), and amount of rice starch as well as nifedipine loading have been investigated. The optimal tablet formulation and the osmotic-suspending co-controlled delivery mechanisms have been proposed. Orifice size and membrane variables including nature and amount of plasticizers as well as thickness on drug release have also been studied. The in vitro release profiles of the optimal system have been evaluated in various release media and different agitation rates, and compared with commercialized conventional capsule and push-pull osmotic tablet. It was found that PEO with MW of 300000 g/mol was suitable to be thickening agent, both amount of KCl and amount of PEO had comparable and profoundly positive effects, while nifedipine loading had a strikingly negative influence on drug release. It could be found that the optimal orifice size was in the range of 0.25-1.41 mm. It has also been observed that hydrophilic plasticizer polyethylene glycol (PEG) improved drug release, whereas hydrophobic plasticizer triacetin depressed drug release when they were incorporated in CA membrane. The monolithic osmotic tablet system was found to be able to deliver nifedipine at the rate of approximate zero-order up to 24 h, independent of both environmental media and agitation rate, and substantially comparable with the push-pull osmotic tablet. The monolithic osmotic tablet system was simple to be prepared as exempting from push layer and simplifying in the orifice drilling compared with the push-pull osmotic tablet. The monolithic osmotic tablet system may be used in drug controlled delivery field, especially suitable for water-insoluble drugs.

Calcium Channel Blockers↗

Selective involvement of reactive oxygen intermediates in platelet-activating factor-mediated activation of NF-kappaB.

Although it has been suggested that some biological activities of platelet-activating factor (PAF) are mediated by, at least in part, reactive oxygen intermediates (ROI), the precise mechanisms underlying the interaction between the two remains to be elucidated. Antioxidants, such as alpha-tocopherol acid succinate, N-acetyl-L-Cysteine, pyrrolidinedithiocarbamate failed to inhibit PAF-induced immediate systemic reactions such as lethality, symptoms of disseminated intravascular coagulation, and histological changes such as pulmonary edema and hemorrhage in renal medullae 10 min following PAF injection. In contrast. antioxidants significantly inhibited both the in vivo and in vitro PAF-induced NF-kappaB activation and NF-kappaB-dependent TNF-alpha expression. The effects of the antioxidants were due to their inhibition of PAF-induced degradation of IkappaBalpha, a protein responsible for keeping NF-kappaB in an inactive form. A protein tyrosine kinase and N-tosyl-L-phenylalanine chloromethyl ketone sensitive serine protease were involved in both PAF- and H2O2-induced NF-kappaB activation. Collectively, these data indicate that the PAF-induced NF-kappaB activation is selectively mediated through the generation of ROI.

Acetylcysteine↗

Gene polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with asthma.

BACKGROUND: Nitric oxide, including that produced by endothelial constitutive nitric oxide synthase (ecNOS), may regulate vascular and airway tone in the lungs and may influence various aspects of airway homeostasis. Angiotensin-converting enzyme (ACE) is expressed at high levels in the lungs and plays a role in the metabolism of angiotensin II, bradykinin, and substance P, all of which are potentially involved in the pathogenesis of asthma. An insertion-deletion polymorphism of the ACE gene has been shown to be associated with enzyme activity levels of ACE. To examine the possible involvement of the ecNOS and/or ACE genes as the genetic basis of bronchial asthma, we investigated whether there was any association between bronchial asthma and polymorphisms of the ecNOS and/or ACE genes. METHODS: A total of 310 patients with bronchial asthma and 121 healthy subjects took part in this study. The ecNOS and ACE genotypes were determined in all subjects by polymerase chain reaction. RESULTS: 1) The distribution of one genotype (bb) of ecNOS was significantly higher in the asthma group than in the control population. 2) The ACE genotype distribution was not significantly different between the control and the asthma groups. 3) In asthmatic patients, the ACE and ecNOS genotype distribution did not differ significantly among groups of patients with different severities of asthma. CONCLUSIONS: These results suggest that polymorphisms of the ecNOS gene, but not the ACE gene, may be associated with the development of asthma. However, the severity of asthma may not be influenced by polymorphisms of the ecNOS and ACE genes.

Adult↗

Reactive oxygen species as glucose signaling molecules in mesangial cells cultured under high glucose.

BACKGROUND: Oxidative stress is one of the important mediators of vascular complications in diabetes including nephropathy. High glucose (HG) generates reactive oxygen species (ROS) as a result of glucose auto-oxidation, metabolism, and formation of advanced glycosylation end products. The concept of ROS-induced tissue injury has recently been revised with the appreciation of new roles for ROS in signaling pathways and gene expression. METHODS AND RESULTS: High glucose rapidly generated dichlorofluorescein-sensitive cytosolic ROS in rat and mouse mesangial cells. Neither L-glucose nor 3-O-methyl-D-glucose increased cytosolic ROS and cytochalasin B, an inhibitor of glucose transporter, effectively inhibited HG-induced ROS generation, suggesting that glucose uptake and subsequent metabolism are required in HG-induced cytosolic ROS generation. H2O2 up-regulated fibronectin mRNA expression and protein synthesis; this up-regulation was effectively inhibited by protein kinase C (PKC) inhibitor or by depletion of PKC. The HG-induced generation of ROS was, in turn, related to activation of PKC and transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) as well as to the up-regulation of transforming growth factor-beta1 (TGF-beta1), fibronectin mRNA expression and protein synthesis, because antioxidants effectively inhibited HG-induced PKC, NF-kappaB, AP-1 activation, and TGF-beta1 and fibronectin expression in mesangial cells cultured under HG. CONCLUSIONS: Although signal transduction pathways linking HG, ROS, PKC, transcription factors, and extracellular matrix (ECM) protein synthesis in mesangial cells have not been fully elucidated, the current data provide evidence that ROS generated by glucose metabolism may act as integral signaling molecules under HG as in other membrane receptor signaling.

Animals↗

Effect of lovastatin on small GTP binding proteins and on TGF-beta1 and fibronectin expression.

We have shown that lovastatin, an inhibitor of 3 hydroxy-3-methylglutary coenzyme A (HMG CoA) reductase, delays development and progression of diabetic nephropathy in streptozotocine-induced diabetic rats through suppression of glomerular transforming growth factor (TGF)-beta1 mRNA expression. We have also shown that lovastatin suppresses both control and high glucose (HG)-induced TGF-beta1 and fibronectin mRNA expression and protein synthesis by rat mesangial cell (RMC) and that this down-regulation by lovastatin is reversed by mevalonate. It was postulated that this down-regulation may be linked to signaling of small guanine triphosphate (GTP)-binding proteins and mediated by the limitation of isoprenoids such as farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) in RMC. To determine the isoprenoid and small GTP-binding proteins involved in TGF-beta1 and fibronectin expression. FPP or GGPP was added alone or in combination to RMC treated with lovastatin cultured under normal or high glucose condition. Suppression of TGF-beta1 and fibronectin expression by lovastatin was reversed effectively when GGPP was added alone. Partial reversal of lovastatin effect on fibronectin and TGF-beta1 expression was found when FPP was added alone. Adding both GGPP and FPP resulted in complete reversal of lovastatin effect on fibronectin but not TGF-beta1 suggesting that fibronectin and TGF-beta1 are regulated differently. Furthermore, luciferase activity of RMC cotransfected with fibronectin promoter reporter system and plasmid-expressing C3 exoenzyme (a specific inactivator of Rho family GTP binding proteins, pEFC3) was completely suppressed when compared with RMC cotransfected with empty vector, pEF. Because geranylgeranylation is usually involved in post-translational modification and membrane targeting of Rho family small GTP binding proteins, these data indicate that Rho family small GTP-binding proteins rather than Ras family small GTP binding proteins may play a key role in the TGF-beta1 and fibronectin expression in RMC.

Animals↗