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Biomedical subjects

Y Lim

Publications and source records attributed to Y Lim.

At least 37 records · Page 2Linked to original sources

Validation of a gastrointestinal explant system for measurement of mucosal antibody production.

A gastrointestinal explant culture system was developed and compared to the mononuclear cell extraction and enzyme-linked immunospot assay method for measurement of immunoglobulin A (IgA) and IgG antibody-secreting cells (ASCs) in gastric antral and duodenal biopsies of non-Helicobacter pylori-infected volunteers. IgA and IgG were detected in explant supernatants during 6 to 7 days of culture in all subjects. IgA containing secretory component was also detected throughout the culture period, although peak production occurred only in the first 3 days. During 7 days of culture, the cumulative geometric mean IgA levels produced were 2.2 and 8.02 microg/ml/10 mg of antral and duodenal biopsy tissues, respectively, while the cumulative geometric mean IgG levels were 1.54 and 2.92 microg/ml/10 mg of antral and duodenal biopsy tissues, respectively. Cycloheximide treatment resulted in a >90% reduction in both immunoglobulin classes after 6 days of treatment compared to levels in untreated controls. The detection of IgA and IgG ASCs extracted from biopsies on days 1 and 6 of culture confirmed that the antibody detected was derived from mucosal lamina propria. The IgA and IgG ASC responses were positively correlated with antibody concentrations detected in culture supernatants (r = 0.87 and 0.85, respectively). These results validate the potential usefulness of our gastrointestinal explant system for the evaluation of mucosal effector B-cell function.

Adolescent↗

Aplastic anemia in a petrochemical factory worker.

A petrochemical worker with aplastic anemia was referred to our hospital. He worked in a petroleum resin-producing factory and had been exposed to low-level benzene while packaging the powder resin and pouring lime into a deactivation tank. According to the yearly environmental survey of the working area, the airborne benzene level was approximately 0.28 ppm. Exposure to benzene, a common chemical used widely in industry, may progressively lead to pancytopenia, aplastic anemia, and leukemia. The hematotoxicity of benzene is related to the amount and duration of exposure. Most risk predictions for benzene exposures have been based on rubber workers who were exposed to high concentrations. In the petroleum industry, the concentration of benzene is relatively low, and there are disputes over the toxicity of low-level benzene because of a lack of evidence. In this paper we report the case of aplastic anemia induced by low-level benzene exposure.

Anemia, Aplastic↗

Environmental measurements of total dust and fiber concentration in manufacturer and user of man-made mineral fibers.

Man-made mineral fibers (MMMF), most of which are referred to as man-made vitreous fibers (MMVF), are mostly amorphous silicates manufactured from glass, rock, or other minerals. Analysis for MMMF have been restricted largely to the measurement of total airborne mass concentrations, but more recently to the determination of airborne fiber levels by phase contrast optical microscopy. In Korea, many small factories are related with manufacturing and using MMMF without any special evaluation of environmental measurements. Though MMMF are known as the substitute of asbestos and their toxicity are regarded as very low, MMMF do not totally excluded from the respiratory and/or skin diseases now. Therefore, we evaluated the environments of many workplaces with total dust and fiber concentration. Most dust and fiber concentrations were below threshold limit value (TLV) at various industries and working processes. However, these data showed a slight relationship between total dust and fiber concentration.

Air Pollutants, Occupational↗

A human transferrin-binding protein of Staphylococcus aureus is immunogenic in vivo and has an epitope in common with human transferrin receptor.

To understand human immune responses against the human transferrin-binding protein of Staphylococcus aureus (SA-tbp), we examined cell wall proteins from S. aureus ATCC 6538 using human convalescent sera, and a monoclonal antibody specific for human transferrin receptor (McAb-HTR). The SA-tbp, detected by immunoblot assay, was iron-repressible, reacted with the convalescent sera, and cross-reacted with McAb-HTR. Immunoelectron microscopy probed with McAb-HTR showed a reaction zone around the test strain from the deferrated BHI. After being preincubated with an S. aureus-bacteremic serum, the electroblot of the SA-tbp still reacted with McAb-HTR, but not with human transferrin-horseradish peroxidase conjugate. We conclude, there are at least two kinds of epitopes in the SA-tbp; one able to bind to human transferrin is immunogenic in humans, but the other sharing epitopes common with human transferrin receptor is not immunogenic in humans.

Antibodies, Bacterial↗

Iron repressibility of siderophore and transferrin-binding protein in Staphylococcus aureus.

In order to investigate whether the iron acquisition mechanisms of Staphylococcus aureus are induced by iron restriction in vitro, we examined S. aureus ATCC 6538 for production of siderophore and expression of transferrin-binding protein (SA-tbp) in normal or deferrated brain heart infusion broth (BHI). Siderophore production was earlier and greater in the deferrated BHI. The SA-tbp, detected by ligand blot assay, was expressed only in the deferrated BHI. When human transferrin was added to the deferrated BHI, siderophore production was later and lower than when transferrin was not present. In conclusion, both iron acquisition mechanisms of S. aureus were found to be iron-repressible and via both of them, human transferrin-bound iron was utilized for growth under iron-restricted condition.

2,2'-Dipyridyl↗

Investigation of the roles of toxin-coregulated pili and mannose-sensitive hemagglutinin pili in the pathogenesis of Vibrio cholerae O139 infection.

In this study, adult volunteers were fed tcpA and mshA deletion mutants of V. cholerae O139 strain CVD 112 to determine the role of toxin-coregulated pili (TCP) and mannose-sensitive hemagglutinin (MSHA) in intestinal colonization. Eight of 10 volunteers who received CVD 112 or CVD 112 delta mshA shed the vaccine strains in their stools; the geometric mean peak excretion for both groups was 1.4 x 10(5) CFU/g of stool. In contrast, only one of nine recipients of CVD 112 delta tcpA shed vibrios in his stool (P < 0.01); during the first 24 h after inoculation, 3 x 10(2) CFU/g was recovered from this volunteer. All recipients of CVD 112 and 8 (80%) of the recipients of CVD 112 delta mshA developed at least a fourfold rise in vibriocidal titer after immunization. In contrast, only one (11%) of the nine recipients of CVD 112 delta tcpA developed a fourfold rise in vibriocidal titer (P < 0.01). We conclude that TCP are an important colonization factor of V. cholerae O139 and probably of El Tor V. cholerae O1. In contrast, MSHA does not appear to promote intestinal colonization in humans.

Adult↗

Effect of silica on phospholipase D activity in rat alveolar macrophages.

Silica may act as a stimulator of pulmonary inflammation and fibrosis. The effect of silica on phospholipase D (PLD) activity assayed as accumulation of [3H]phosphatidylethanol ([3H]PtdEt) was examined in [3H]palmitic acid-labeled primary cultures of rat alveolar macrophages. Silica induced a rapid accumulation of [3H]PtdEt in a time (0, 15, 30 and 45 min)- and concentration (0.5, 1.0, 2.5 and 5.0 mg/ml)-dependent manner indicating PLD activation. This silica-stimulated PLD activity was attenuated by the pretreatment with calcium chelator ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) or/and 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester (BAPTA/AM) (EGTA: 54.3 +/- 8.6%, BAPTA/AM: 67.5 +/- 7.8% and EGTA + BAPTA/AM: 35.8 +/- 2.9, respectively). Also, silica-induced PLD activation was partially inhibited by the pretreatment with nonspecific phospholipase C (PLC) and PLD inhibitor (neomycin; 66.4 +/- 4.8%) or specific PLC inhibitor (U73122; 70.8 +/- 4.6%). Sphingosine as a protein kinase C (PKC) inhibitor did not change silica-induced PLD activity indicating that PKC might not play a role in PLD activation by silica. Based on these results, we concluded that a silica-stimulated phospholipase D activity is present in the rat alveolar macrophages and is predominantly regulated by PLC-mediated intracellular calcium.

Analysis of Variance↗

Pasteurella multocida epiglottitis.

Pasteurella multocida, a small gram-negative coccobacillus, colonizes the nasopharynx and gastrointestinal tract of many animals, including cats and dogs. Most human infections with P multocida are due to animal bites, but the respiratory tract is the second most common site of infection. We describe the third case report (to out knowledge) of acute P multocida epiglottitis. The mode of transmission in this case was inhalation of infectious nasopharyngeal secretions from cats. The patient responded well to treatment with penicillin, the drug of choice for P multocida infections. Therefore, infection with P multocida, though rare, should be considered in the differential diagnosis in any case involving acute epiglottitis and exposure to cats.

Acute Disease↗

Audit of waste collected over one week from ten dental practices. A pilot study.

An audit of the waste practices of ten general dental surgeries identified problems that have occurred due to the lack of specific dental guidelines or codes of practice in this area. Occupational health and safety requirements for types and locations of sharps containers, and lack of consensus on what constitutes a sharp, were identified as areas needing attention. Cross-infection control items, such as gloves, masks, single-use cups, and protective coverings, were found to constitute up to 91 per cent of total waste. When infectious waste was reclassified by the audit team as 'that waste which was visibly blood stained,' a reduction in waste in this category was made, during the audit, at each practice. The practice of disposing of radiographic fixer and developer into the sewerage system occurred in three out of the ten practices, even though the Australian Dental Association Inc. has discouraged this practice.

Blood↗

Vibriocidal antibody responses in North American volunteers exposed to wild-type or vaccine Vibrio cholerae O139: specificity and relevance to immunity.

The emergence of a new agent of cholera, Vibrio cholerae O139, has prompted a reevaluation of the vibriocidal antibody assay. This assay, primarily directed to lipopolysaccharide, is an important correlate of O1 immunity. V. cholerae O139 strains are encapsulated, rendering them relatively resistant to killing by serum. Recent reports suggest that there is strain-to-strain variability in the sensitivity of the vibriocidal assay to fully encapsulated O139 strains. We have assessed a modified vibriocidal assay for fully encapsulated O139 strain AI-1837 and its unencapsulated mutant 2L in sera from 53 volunteers given wild-type AI-1837 or its attenuated derivative CVD 112 and from 48 controls challenged with V. cholerae O1 or strains of the family Enterobacteriaceae. Vibriocidal responses to the AI-1837 and 2L strains were seen in 67 and 89% of volunteers, respectively, following a single exposure to the wild-type strain. However, >50% of all controls had low-level vibriocidal responses to both strains. These nonspecific responses were transient and of the immunoglobulin G isotype. No binding activity against purified O139 lipopolysaccharide (LPS) by immunoblotting was seen in control sera. In contrast, vibriocidal assay and strain 2L LPS responses by immunoblotting were detectable in 91% of tested volunteers following a single exposure to O139. The presence of vibriocidal antibody to AI-1837 or 2L was not associated with protection in rechallenge studies with O139 strain AI-1837. The vibriocidal assay with unencapsulated strain 2L may be used to detect exposure to O139 strain AI-1837 in controlled research trials. However, its lack of specificity does not make it useful for determining exposure to V. cholerae O139 in the field.

Antibodies, Bacterial↗

Involvement of protein kinase C, phospholipase C, and protein tyrosine kinase pathways in oxygen radical generation by asbestos-stimulated alveolar macrophage.

Although asbestos stimulates oxygen radical generation in alveolar macrophages, the exact mechanism is still not clear. The purpose of this study was to compare the ability of three asbestos fibers (amosite, chrysotile, and crocidolite) to generate oxygen radicals in macrophages and examine the mechanism of this action. All asbestos fibers were able to induce chemiluminescence but chrysotile induced maximal chemiluminescence at higher concentrations than amosite and crocidolite. Protein kinase C (PKC) inhibitors (sphingosine and staurosporine) suppressed the ability of asbestos to induce oxygen radical generation. Phospholipase C (PLC) inhibitors (U73122 and neomycin) and protein tyrosine kinase (PTK) inhibitors (erbstatin and genistein) decreased oxygen radical generation of asbestos-stimulated alveolar macrophages. Oxygen radical generation was not suppressed by an adenylate cyclase activator (forskolin), a protein kinase A inhibitor (H-8), and a protein serine-threonine phosphatase inhibitor (okadaic acid). PLC and PTK inhibitors suppressed the increment of phosphoinositide turnover by amosite. These results suggest that asbestos fibers induce the generation of oxygen radicals through PTK, PLC, and PKC pathways in a dose-response pattern.

Animals↗

Silica-induced oxygen radical generation in alveolar macrophage.

Silica is a well-known occupational fibrogenic agent and its primary target cell is alveolar macrophage. Particle-stimulated macrophages are believed to release various mediator which can regulate the inflammation as well as pulmonary fibrosis. Even though oxygen radicals play the major role among these mediators, the mechanisms concerning the stimulation of alveolar macrophages are not clear yet. The present study was carried out to investigate the signal transduction pathway on oxygen radical generation in silica-stimulated alveolar macrophages. Silica induced oxygen radical generation in a dose-response pattern. Extracellular calcium depletion, calcium channel blockers, and calcium release blocker decreased the effect of silica on oxygen radical generation. Silica increased intracellular calcium through the influx of calcium through the calcium channel and the calcium release from the intracellular calcium store. To know the role of protein kinase C (PKC), phospholipase C (PLC), and protein tyrosine kinase (PTK) in silica-induced oxygen radical generation, we pretreated alveolar macrophages with inhibitors of these enzymes. Inhibitors of PKC (sphingosine and staurosporine), PLC (neomycin and U-73122), and PTK (genistein and erbstatin) suppressed the silica-induced oxygen radical generation. Silica increased the PLC activity at the concentration of 5 mg/ml. The inhibitors of PTK and PLC suppressed the action of silica on the PLC activity. From these results, we suggest that silica induces oxygen radical generation through PTK, PLC, and PKC in alveolar macrophages.

Animals↗

The intratracheal administration of endotoxin: X. Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo.

Intratracheal instillation of endotoxin (LPS) causes acute pulmonary inflammation characterized by the accumulation of plasma proteins and leukocytes within the pulmonary airways. The synthetic glucocorticoid dexamethasone 1) inhibits the LPS-initiated vascular leak of plasma proteins into the airspace, 2) inhibits the LPS-initiated emigration of neutrophils and lymphocytes into the airspace in a dose-dependent fashion, and 3) inhibits LPS-initiated mRNA and/or bronchoalveolar lavage protein expression of cytokines (TNF, IL-1 and IL-6) and chemokines (MIP-1 alpha, MIP-2 and MCP-1). In conclusion, dexamethasone inhibits both the vascular and cellular aspects of acute inflammation by downregulation of a broad spectrum of inflammatory cytokines and chemokines.

Animals↗

AL072, a novel anti-Legionella antibiotic produced by Streptomyces sp.

AL072 is a potent anti-Legionella antibiotic produced by Streptomyces strain AL91. The compound was isolated from the fermentation broth with 1 volume of isopropyl alcohol, followed by an ethyl acetate extraction and subsequent concentration under reduced pressure. Purification was performed on an octadecyl silica gel column followed by preparative HPLC. AL072 purified as mentioned above showed extremely specific activity only towards Legionella pneumophila. No antibacterial activity against any other bacteria tested was demonstrable. Its molecular weight was determined by FAB-MS (m/z 648) and the compound was identified as a novel 1,3-diacyl glycerol with the molecular formula C41H76O5. One of the two acyl groups is linoleyl and the other is 3,5-dimethyl octadecanoyl.

Anti-Bacterial Agents↗

Cepacidine A, a novel antifungal antibiotic produced by Pseudomonas cepacia. I. Taxonomy, production, isolation and biological activity.

Cepacidine A is a potent antifungal antibiotic produced by Pseudomonas cepacia AF 2001. The compound was isolated from the fermentation broth with 1 vol isopropyl alcohol, followed by the collection of the precipitation formed upon concentration of the extract. Purification was effected by chromatography on Diaion HP-20, alumina and reversed phase C18 followed by TLC on silica gel. These techniques afforded the two closely related compounds, cepacidine A1 and cepacidine A2. A mixture of these two compounds called capacidine A, showed high in vitro antifungal activity against the various animal and plant pathogenic fungi. The activity was diminished by the presence of serum. No antibacterial activity was demonstrable.

Anti-Bacterial Agents↗

Cepacidine A, a novel antifungal antibiotic produced by Pseudomonas cepacia. II. Physico-chemical properties and structure elucidation.

Cepacidine A is a novel glycopeptide with a potent antifungal activity, which is produced by Pseudomonas cepacia AF 2001. Its molecular weight was determined by FAB-MS (m/z 1215). The compound is comprised of glycine (1), serine (2), 2,4-diaminobutyric acid (1), aspartic acid (1), beta-hydroxy tyrosine (1), beta-hydroxy asparagine (1), xylose (1) and 5,7-dihydroxy-3,9-diamino-octadecanoic acid (1). Unfortunately, cepacidine A is a mixture of A1 and A2, either of which is barely distinguishable. Cepacidine A2 includes asparagine (1) instead of beta-hydroxy asparagine (1) of cepacidine A1. The MS data and the NOESY, TOCSY and HMBC spectra show that cepacidine A is a cyclic peptide and xylose is connected to 5,7-dihydroxy-3,9-diaminooctadecanoic acid.

Anti-Bacterial Agents↗

Systemic and mucosal immune responses to rhesus rotavirus vaccine MMU 18006.

Thirty-four children 3 to 20 months of age ingested either 10(5), 10(4) or 10(3) plaque-forming units of rhesus rotavirus vaccine, MMU 18006, which possesses human rotavirus serotype 3 neutralization antigen. Immune responses were evaluated by a plaque reduction neutralization (PRN) assay to rotavirus serotypes 1, 2 and 3 and by a serum IgG, IgM and IgA and fecal IgA class-specific enzyme-linked immunosorbent assay. Homotypic PRN antibody seroconversions to serotype 3 rotavirus were detected in 31 of 34 children (91%), whereas rises in heterotypic PRN antibody to human rotavirus serotypes 1 or 2 were found in only 3 of 21 (14%) (p less than 0.00000001). Thirty of the 34 vaccinated children (88%) had at least one class of rotavirus-specific serum antibody detected by enzyme-linked immunosorbent assay. A rotavirus-specific IgA coproantibody response was seen in 11 of 16 children (69%) following vaccination. Two children who had no evidence of PRN antibody to serotype 3 after vaccination had evidence of both a fecal and a serum rotavirus-specific IgA response, suggesting that in these children the response to the vaccine was primarily mucosal. These data show that orally administered rhesus rotavirus vaccine MMU 18006 elicits local intestinal immunity but produces primarily a homotypic serum neutralization response as measured by plaque reduction neutralization assays.

Antibodies, Viral↗