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Biomedical subjects

H Choi

Publications and source records attributed to H Choi.

At least 127 records · Page 7Linked to original sources
PubMed1997

Role of particulate antigens of Aspergillus in murine eosinophilia.

OBJECTIVE: Allergic bronchopulmonary aspergillosis, a disabling hypersensitivity lung disease, results from inhalation of Aspergillus fumigatus antigens present in contaminated environments. A murine model has been developed to understand the immune mechanism involved in allergic bronchopulmonary aspergillosis. We have investigated the immunoregulatory role of different physical forms of A.fumigatus antigens, such as A.fumigatus spores, soluble antigens. and soluble antigen coupled inert particles, in the model. METHODS: BALB/c mice were exposed to soluble A.fumigatus antigens, spores, or inert particles of comparable size to the spores coupled with A.fumigatus soluble antigens. Antibody and eosinophil response, pulmonary pathology, and cytokine expressions were studied. RESULTS: Peripheral blood eosinophilia and pulmonary inflammation with influx of eosinophils into the lung was detected more in animals exposed to particulate antigens than in those exposed to soluble antigen. However, the total serum IgE and Aspergillus-specific IgG levels showed only a slight increase in the former groups as opposed to elevated levels in animals exposed to soluble antigen. The cytokine expression in in vitro antigen stimulated spleen cells showed a typical Th2 pattern in all antigen-exposed animals. IL-5 mRNA could be detected in the spleen cells cultured with antigen from all groups of antigen-exposed animals. CONCLUSION: Particulate A.fumigatus antigens induced eosinophilia in mice prior to the elevation of serum IgE levels. This pattern of IgE and eosinophilia is reversed with the soluble antigen exposure in this model.

Animals↗
PubMed1997

Combination of tracheal gas insufflation and airway pressure release ventilation.

STUDY OBJECTIVE: We hypothesized that the continuous gas flow administration delivered through an insufflation catheter positioned above the carina during airway pressure release ventilation (APRV) would facilitate carbon dioxide (CO2) elimination, resulting in normocarbia with a substantially reduced peak airway pressure (Paw). To test this hypothesis, we compared intermittent positive pressure ventilation (IPPV), tracheal gas insufflation (TGI), APRV, and combined TGI and APRV (TGI + APRV). DESIGN: Animal study with random application of four ventilatory modes in a canine restrictive-thorax model with and without pulmonary edema. SETTING: Research laboratory at Kumamoto (Japan) University School of Medicine. SUBJECTS: Six mongrel dogs. INTERVENTIONS: Application of four ventilatory modes (IPPV, TGI, APRV, and TGI + APRV). MEASUREMENTS AND RESULTS: TGI + APRV facilitated CO2 elimination. The peak Paw was significantly lower during TGI + APRV than during IPPV (nonpulmonary edema model; 15 +/- 4 vs 28 +/- 9 cm H2O; p < 0.05; pulmonary edema model: 20 +/- 4 vs 34 +/- 10 cm H2O; p < 0.05). Normocarbia was observed in both models. Neither TGI nor APRV alone maintained normocarbia. CONCLUSION: The combined use of TGI and APRV is a more effective method of maintaining normocarbia with reduced peak Paw than either IPPV or APRV alone.

Animals↗
PubMed1996

Recombinant adenovirus deleted of all viral genes for gene therapy of cystic fibrosis.

Recombinant adenoviruses are being developed for gene therapy of inherited disorders such as cystic fibrosis because they efficiently transduce recombinant genes into nondividing cells in vivo. First generation recombinant adenoviruses, rendered defective by deletion of sequences spanning E1a and E1b, express low levels of early and late viral genes that activate destructive cellular immune responses. Current strategies for improving recombinant adenoviruses attempt to inactivate other essential genes through deletion and growth in new packaging cell lines or incorporation of temperature sensitive mutations which allow propagation of the virus in available packaging cell lines at permissive temperatures. We describe in this report a new type of recombinant adenovirus that is deleted of all viral open reading frames. This recombinant (called delta-rAd), which contains only the essential cis elements (i.e., ITRs and contiguous packaging sequence), is propagated in 293 cells in the presence of E1-deleted helper virus. Concatamers of the monomeric vector genome were passaged and capable of transduction. The delta-rAd genome is packaged into virions that sediment at a lower density than the helper virus in cesium gradients forming the basis for a purification protocol. A fully deleted recombinant adenovirus that expresses human cystic fibrosis transmembrane conductance regulator was produced and used to transduce human airway epithelial cells derived from a cystic fibrosis patient. Packaging and propagation of a fully deleted adenovirus is an important step toward the development of a safer vector. Improved production and purification strategies need to be developed before this new vector system can be evaluated in vivo.

Adenoviridae↗
PubMed1996

Anatomic delineation of the ulnar nerve and ulnar artery in relation to the carpal tunnel by axial magnetic resonance imaging scanning.

In a number of publications the distal branches of both the ulnar artery and ulnar nerve have been identified as being positioned ulnar to the hook of the hamate. We undertook a magnetic resonance imaging project in patients who presented for carpal tunnel release to determine how far radially vital structures of Guyon's canal may be located and if they may overlap the carpal tunnel at the hook of the hamate. Cross-sectional magnetic resonance imaging scans of 20 patients were performed prior to carpal tunnel release with the wrist positioned in neutral, flexed, and extended positions. Linear measurements were made either radial or ulnar to the hook of the hamate taken as the reference point. In the neutral position, the ulnar nerve was found to be, on average, 3.6 mm ulnar to the hook of the hamate (range of 5.8 mm radial to 7.5 mm ulnar). The ulnar artery averaged 0.7 mm to the radial side of the hook of the hamate (range 7.8 mm radial to 2.8 mm ulnar). Guyon's canal extended 28% of the way across the carpal ligament (range 9 to 63%). With the wrist in flexion and extension, there was an ulnar displacement and a radial displacement, respectively, of these structures relative to the hook of the hamate.

Carpal Bones↗
PubMed1995

Catalytically active forms of the individual subunits of Vibrio harveyi luciferase and their kinetic and binding properties.

Contradictory findings have recently been reported regarding the (in)abilities of individual subunits of the Vibrio harveyi alpha beta dimeric luciferase to catalyze bioluminescence. We have produced individual alpha and beta subunits separately in Escherichia coli JM109 cells by recombinant DNA techniques. Both subunits were purified to more than 90% homogeneity and found to be catalytically active, with their general catalytic properties and the specific activities similar to those reported earlier (Sinclair, J. F., Waddle, J. J., Waddill, E. F., and Baldwin, T. O. (1993) Biochemistry 32, 5036-5044). Individual subunits were significantly distinct from the native luciferase with respect to inactivations by trypsin and N-ethylmaleimide, and the stability of the flavin 4a-hydroperoxide intermediate. The active species in isolated alpha and beta samples were each the predominant protein species, corresponding to a 42,000 M(r) alpha monomer and a 67,000 M(r) beta dimer, respectively. These findings clearly indicate that the activities of the individual subunits are not due to trace contaminations of the respective counter subunits. The much reduced specific activities of the individual subunits are, in part, a consequence of diminished abilities to oxidize the aldehyde substrate. Kinetic and equilibrium measurements indicate that alpha and beta 2 each contained a reduced flavin site, an aldehyde substrate site, and an aldehyde inhibitor site. The on and off rates of the decanal inhibitor binding were substantially slower than the bindings of decanal and reduced riboflavin 5'-phosphate substrates. These findings are consistent with a scheme that the aldehyde inhibitor blocks the binding of the reduced flavin substrate.

Binding Sites↗
PubMed1995

Interferon-gamma and tumor necrosis factor-alpha protect mice from invasive aspergillosis.

The immunopathogenesis of invasive aspergillosis and the role played by cytokines are not fully understood. The roles of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were investigated in BALB/c mice infected intravenously with 5 x 10(5) Aspergillus fumigatus conidia. Eight groups of animals were studied, including 2 control groups (mice only infected with A. fumigatus and those given cortisone acetate and infected with A. fumigatus) and 6 groups of infected mice either treated or not treated with cortisone acetate and given IFN-gamma, anti-IFN-gamma, TNF-alpha, or anti-TNF-alpha. No deaths occurred among the mice treated with IFN-gamma and TNF-alpha, compared with 40%-80% mortality in the other groups. IFN-gamma- and TNF-alpha-treated mice also had fewer organs from which A. fumigatus could be cultured or demonstrated on histologic examination. These observations suggest that IFN-gamma and TNF-alpha have protective roles in invasive aspergillosis.

Animals↗
PubMed1995

Pigeon-serum-induced hypersensitivity pneumonitis in the dog.

Pigeon serum (PS) is one of the most common causes of hypersensitivity pneumonitis (HP). PS-induced HP was examined in a dog model. The dogs (n = 6) were immunized by i.m. injections of PS, followed by insufflation with aerosolized PS, while all control dogs (n = 3) received saline only. All animals insufflated with PS developed tachypnea 2-4 h after PS inhalation. After PS insufflation, a significant decrease in arterial oxygen tension (PaO2) was detected in sensitized dogs. No change in PaO2 was detected in sensitized dogs after saline or in the controls after PS insufflation. In intradermal skin tests with PS antigen, a positive skin reaction was found in 3/6 dogs in 30 min, and in 5/6 dogs in 6 and 48 h after the PS injections. Sensitized dogs showed a significant increase in PS-specific IgG in serum and lavage fluid (LF). In LF of sensitized dogs, an increase in the percentage of lymphocytes, eosinophils, and neutrophils was detected. Sensitized dogs developed chronic interstitial inflammation with lymphocytes, macrophages, plasma cells, and eosinophils in lungs. Granulomas with lymphocytes, histiocytes, and giant cells were detected in both the interstitium and the bronchiolar wall in the lungs of sensitized dogs. PaO2 was lowest in dogs showing the most severe interstitial inflammation in the lungs. The results indicate that dogs can be successfully used in immunologic and physiologic studies of PS-induced HP.

Alveolitis, Extrinsic Allergic↗
PubMed1995

Percutaneous drainage of splenic abscess in typhoid fever--a case report.

Salmonella typhi splenic abscesses are a very rare complication of typhoid fever. Splenectomy is the standard surgical treatment for these lesions. But these days, with improvements in imaging techniques, percutaneous drainage of splenic abscesses has been demonstrated to be one of the alternative treatment in selected cases. We report the case of a 7 year-old male, who presented with Salmonella typhi in blood and urine cultures, and a 1: 320 in O titer of Widal test. Ultrasound and computed tomography showed a single splenic abscess, 3 cm in diameter. He was treated with antibiotics, but the symptoms were not relieved. Thus we performed the percutaneous drainage of the splenic abscess under ultrasound guidance. A culture of the aspirated material was positive for Salmonella typhi, and the boy's condition improved. We think that percutaneous drainage of a single lesion was an excellent alternative to surgery, particularly because our patient was young and spleen conservation was desirable.

Abscess↗
PubMed1994

Stopped lower buffer flow electrofractionation: simple electrofractionation for complex protein mixture.

The standard electrofractionation technique simulated the liquid chromatography to create a continuous elution system. Though this continuous lower buffer flow electrofractionation system served as an excellent model for preparative electrophoresis, the restricted current flow caused by electric resistance arising from the column holder prevented the application to the purification of complex protein mixtures. To overcome the electric current problem, the stopped lower buffer flow electrofractionation (SFE) system is designed to work without using a column holder and use prestained markers as the detection tool of protein position during the electrofractionation process. Through this improvement, the SFE system widens the availability of electrofractionation to the purification of complex and low-concentration protein mixtures. In this report, the efficiency of this technique is shown through the partial purification of a 32P-labeled protein in the rat liver microsome.

Animals↗
PubMed1994

Preparation of mixed ligand immobilized artificial membranes for predicting drug binding to membranes.

Mixed ligand immobilized artificial membranes (IAMs) are surfaces that contain at least two immobilized membrane phospholipids which are designated as either the primary phospholipid or the secondary phospholipid. The primary immobilized phospholipid refers to the immobilized phospholipid that has the highest surface density. For this work, the primary immobilized phospholipid was a single-chain ether phosphatidylcholine (PC) analog. Four mixed-ligand IAMs were prepared by use of immobilized PC as the primary immobilized phospholipid. The secondary immobilized phospholipid ligand was either phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, or phosphatidic acid. All of these secondary phospholipids are bonded at approximately 6-10 mol % relative to the molar amount of immobilized PC. Each secondary phospholipid contains functional groups in the polar head group region that require protecting groups during the immobilization process. The four-step synthetic strategy to prepare mixed-ligand IAMs involves (i) immobilization of the PC analog at high density to silica propylamine (SPA), (ii) immobilization of the second phospholipid (PL) analog at low density, (iii) end capping residual amines with a long-chain anhydride followed by end capping with a short-chain anhydride, and (iv) deprotection of the polar head group protecting groups. The surface density of the mixed PLs bonded to the silica support was approximately 130 mumol of PLs/g of SPA. High-performance liquid chromatography using these mixed lipid IAMs can be exploited to rapidly predict the membrane binding properties of drugs.

Adrenergic alpha-Agonists↗
PubMed1994

Two craniosynostotic syndrome loci, Crouzon and Jackson-Weiss, map to chromosome 10q23-q26.

Crouzon syndrome (MIM 123500) is a common autosomal dominant form of craniosynostosis with shallow orbits, ocular proptosis, and maxillary hypoplasia. Jackson-Weiss syndrome (MIM 123150) is another autosomal dominant craniosynostosis with highly variable phenotypic expression. Unlike Crouzon syndrome, Jackson-Weiss syndrome is associated with foot anomalies. We performed two point linkage and haplotype analyses using 13 dinucleotide repeat markers on chromosome 10, spanning a genetic distance of 108 cM. The Crouzon syndrome locus (CFD1) maps to the region of chromosome 10q2, with the tightest linkage to locus D10S205 (Z = 3.09, theta = 0.00). the Jackson-Weiss syndrome locus in the large Amish pedigree in which the condition was originally described was also linked to the chromosome 10q23-q26 region between loci D10S190 and D10S186. The D10S209 locus was most strongly linked (Z = 11.29, theta = 0.00).

Abnormalities, Multiple↗
PubMed1994

Inhibitors of sterol synthesis: synthesis and spectral properties of derivatives of 3 beta-hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholest-8(14)-en-15-one fluorinated at carbon 7 or carbon 9 and their effects on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured mammalian cells.

As part of a program to prepare delta 8(14)-15-ketosterols that cannot readily be metabolized to cholesterol or side-chain oxygenated species, we have prepared 3 beta-hydroxy-7 alpha-fluoro-5 alpha-cholest-8(14)-en-15-one (VII) and the 9 alpha-hydroxy (IV), 9 alpha-fluoro (VI) and 7 alpha-fluoro (VIII) derivatives of 3 beta-hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholest-8(14)-en-15-one (II). Sterol IV was prepared by oxidation of the delta 8,14 dienol ethyl ether of the 3 beta-acetate of II with m-chloroperbenzoic acid, followed by mild alkaline hydrolysis of the 3 beta-acetate derivative of IV. Treatment of IV with hydrogen fluoride-pyridine gave VI. The 7 alpha-fluoro-15-ketosterols VII and VIII were synthesized by treating the 3 beta,15-bis-trimethylsilyl delta 7,14-dienol ether derivative of the appropriate delta 8(14)-15-ketosterol with N-fluoropyridinium triflate, followed by hydrolysis of residual trimethylsilyl ethers and purification by high-performance liquid chromatography. The combined results of 1H and 13C nuclear magnetic resonance (NMR) chemical shifts, 1H-1H coupling constants, 1H-19F long-range coupling constants and molecular modeling indicated that a 7 alpha-fluoro, 9 alpha-fluoro or 9 alpha-hydroxy substituent has negligible effect on the conformation of the 15-ketosterols. 1H and 13C-NMR data are also given for delta 6,8(14)- and delta 8(14),9(11)-15-ketosterols, synthetic byproducts that could not be detected readily in samples of the fluoro-15-ketosterols by chromatographic methods. Mass spectra of VI and of previously reported 9 alpha-fluoro and 9 alpha-hydroxy-delta 8(14)-15-ketosterols showed abundant M-62 or M-60 ions that appear to correspond to loss of ketene and HF or H2O. The 9 alpha-hydroxy-F7-15-ketosterol IV, the 7 alpha-fluoro-15-ketosterol VII and the 7 alpha-fluoro-F7-15-ketosterol VIII were of equivalent potency to the parent 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (I) in lowering the levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in CHO-K1 cells. The 9 alpha-fluoro-F7-15-ketosterol VI showed high potency but appeared to be slightly less active than I.

Animals↗
PubMed1994

Hyperimmune serum modulates allergic response to spores in a murine model of allergic aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a disease in atopic asthmatics characterized by eosinophilia and elevated levels of immunoglobulin E (IgE) and IgG antibodies to the ubiquitous fungus Aspergillus fumigatus (Af). The role of specific antibodies in the disease process is not clear. In this study, BALB/c mice were injected with hyperimmune serum from syngeneic mice exposed to soluble antigen of Af. These mice were then exposed to either Af spores or soluble antigen. Total IgE, Af-specific IgG1 (enzyme-linked immunosorbent assay) in serum, and eosinophils (eosinophil peroxidase assay) in lungs and bone marrow were measured. Histologic sections of lungs were examined for cellular infiltration and morphologic changes. Results indicate a suppression of increase in levels of antibodies and eosinophilia in mice receiving immune serum and exposed to spores compared with controls receiving phosphate-buffered saline treatment. Spores being the primary source of exposure to Af in ABPA, these results are significant in understanding the role of preexisting specific antibodies in patients.

Animals↗
PubMed1994

IgE and eosinophil regulation in a murine model of allergic aspergillosis.

Exposure of BALB/c mice to Aspergillus fumigatus (Af), the antigen responsible for causing allergic bronchopulmonary aspergillosis in humans, caused elevated levels of serum immunoglobulin E (IgE) and peripheral blood and lung eosinophilia similar to that observed in the human disease. We have investigated the role of interleukin-4 (IL-4), IL-5 and interferon-gamma in regulating IgE and eosinophilia in the mouse model. Animals were immunized by intraperitoneal injections of soluble Af antigens adsorbed to alum. These animals developed elevated IgE and Af specific IgG1 and were then treated with anticytokine monoclonal antibodies before the final exposure to particulate Af antigens by the intranasal route. The results showed that anti-IL-5 abrogated eosinophilia in mice, while those treated with anti-IL-4 retained the same or reduced IgE levels compared to pretreatment levels. All anti-IL-5, anti-IFN-gamma, and control antibody-treated animals showed enhanced IgE levels. Anti-IFN-gamma treatment of mice resulted in marked enhancement of eosinophilia compared to all other groups. Eosinophil numbers observed in the histological sections of the lungs confirmed the eosinophilia detected in the peripheral blood. These results indicate that the increase in IgE and eosinophils after exposure to Af antigens in BALB/c mice are due to Af-induced production of IL-4 and IL-5 and that both IgE and eosinophilia are independently regulated.

Animals↗
PubMed1994

Latex-induced dermal and pulmonary hypersensitivity in rabbits.

BACKGROUND: Natural rubber latex (NRL) causes immediate, IgE-mast cell-mediated reactions in sensitized individuals, especially among health care workers and children with spina bifida. The immunopathogenesis of the reaction is obscure. METHODS: To study the immunologic mechanisms of NRL allergy, rabbits were sensitized with two nonammoniated and one ammoniated NRL antigens. Subcutaneous and intratracheal injections were used to immunize rabbits. Intradermal skin tests, IgG antibodies against NRL in serum and lung lavage fluid, and pulmonary histologic features were evaluated. RESULTS: One of nine sensitized rabbits died of anaphylaxis immediately after the third intratracheal injection with nonammoniated NRL. All sensitized rabbits, but not the controls, showed an immediate wheal and flare reaction in intradermal skin testing with NRL antigens. A positive skin reaction was detected 6 and 48 hours after the intradermal injections in four of five sensitized rabbits. A significant increase in NRL-specific IgG antibodies was detected in serum and lung lavage fluid of immunized rabbits. Lung histologic evaluation of NRL-sensitized rabbits showed a granulomatous interstitial and bronchial inflammation with a predominance of eosinophils and histiocytes in both intratracheally and subcutaneously sensitized rabbits. Vasculitis, hypertrophia, and contraction of pulmonary arteries could be detected in sensitized animals. CONCLUSION: The results of the first NRL rabbit model study indicate that eosinophils and IgE antibodies play a major role in the immunopathogenesis of NRL-induced allergy and anaphylaxis. A wide range of inflammatory responses detected in rabbits injected by subcutaneous route without intratracheal exposure suggests that NRL exposure may pose a risk for a subsequent systemic reaction.

Anaphylaxis↗
PubMed1994

Particulate Aspergillus fumigatus antigens elicit a TH2 response in BALB/c mice.

BACKGROUND: In order to understand the immunoregulation in allergic aspergillosis, a murine model was developed by exposing animals to particulate and soluble antigens of Aspergillus fumigatus. METHODS: BALB/c mice were exposed to soluble Aspergillus antigen intranasally. Animals showing moderate levels of IgE were subsequently exposed to soluble antigen or antigen conjugated to polystyrene beads intranasally. The IgE and IgG1 in the sera and the eosinophils in the blood and lungs were studied. The spleen and lung mononuclear cells were stimulated with both concanavalin A and antigen and evaluated for production of interleukin (IL)-4, IL-5, IL-10, and interferon-gamma. RESULTS: Animals exposed to particulate antigens showed more elevated serum IgE levels and increased numbers of eosinophils in the blood and lungs than those exposed to soluble antigen. Lung cell cultures from animals exposed to particulate antigens when stimulated with Aspergillus produced IL-4 and IL-5, indicating a TH2 type of response. Animals exposed to soluble antigens showed a weaker TH2 response, as evidence by low IgE levels in sera, fewer eosinophils in the blood, and low levels of cytokine production from lung and spleen cells. CONCLUSION: The results indicate that the physical nature of the antigen may have a major role in determining the type of immune response of the host.

Administration, Inhalation↗
PubMed1994

Effects of midazolam and flumazenil on carotid sinus baroreflex control of circulation in rabbits.

We have studied the effects of midazolam and flumazenil on the carotid sinus baroreflex, by examining mean arterial pressure (MAP) and heart rate (HR) responses to partial or complete bilateral carotid occlusion (BCO) in 12 conscious rabbits after aortic denervation. In eight rabbits, the responses to complete BCO were evaluated before and after cumulative doses of midazolam 0.5 and 1.0 mg kg-1, and after flumazenil 0.3 mg kg-1 following administration of midazolam. Midazolam and flumazenil had no effect on MAP or HR before complete BCO and neither affected the MAP response to complete BCO. Midazolam 0.5 and 1.0 mg kg-1 decreased the HR response to 60% and 58% of control, respectively. Flumazenil restored the midazolam-induced depression of the HR response to the control level. In the other four rabbits, we examined the MAP and HR responses to partial BCO (carotid artery pressure reduced by 5, 10 and 20 mm Hg) before and after midazolam 0.5 mg kg-1 and after flumazenil 0.3 mg kg-1 following administration of midazolam. The response to partial occlusion showed the same tendency as the response to complete BCO. These results indicate that midazolam attenuated the HR response of the carotid sinus baroreflex, flumazenil restored this midazolam-induced depression and neither drug affected the MAP response.

Animals↗