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Biomedical subjects

O S Kwon

Publications and source records attributed to O S Kwon.

At least 37 records · Page 2Linked to original sources
PubMed2000

Identification of propentofylline metabolites in rats by gas chromatography/mass spectrometry.

Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been reported to be a compound for treatment of both vascular dementia and dementia of the Alzheimer type. The short half-life (about 15 min) of PPF at the terminal elimination phase and poor bioavailability after oral administration of PPF to rabbits (Kim et al., 1992) suggest in part that this drug takes the extensive first-pass metabolism in the liver. In addition, the metabolic pathway for PPF remains unclear. The objective of this experiment is to identify urinary metabolites of PPF in rats. For the identification of the metabolites, rat urine was collected after oral administration of 100 mg/kg PPF. PPF metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine, was synthesized and confirmed by gas chromatography/mass spectroscopy (GC/MS) and 1H nuclear magnetic resonance spectroscopy. The urinary metabolites of PPF were extracted with diethyl ether and identified by electron impact and chemical ionization GC/MS. One urinary metabolite was confirmed to be 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine by synthesized authentic compound. Several metabolites of monohydroxy- and dihydroxy-PPF were identified based on mass fragmentation of both intact and trimethylsilylated derivatives of PPF metabolites and the novel structure of these metabolites is suggested based on mass spectra.

Animals↗
PubMed2000

Human brain GABA transaminase tissue distribution and molecular expression.

Human brain gamma-aminobutyrate transaminase is differentially expressed in a tissue-specific manner. mRNA master dot-blot analysis for 50 different human tissues, including different brain regions and fetal tissues, provided a complete map of the tissue distribution. Genomic Southern analysis revealed that the gamma-aminobutyrate transaminase gene is a single copy, at least 15 kb in size. In addition, human brain gamma-aminobutyrate transaminase cDNA was expressed in Escherichia coli using a pGEX expression vector system. Catalytically active gamma-aminobutyrate transaminase was expressed in large quantities and the purified recombinant enzyme had kinetic parameters that were indistinguishable from those isolated from other mammalian brains. The human enzyme was inactivated by a well-known antiepileptic drug vigabatrin. Values of Ki and kinact were 1 mM and 0.35 min-1, respectively. Results from inactivation kinetics suggested that human gamma-aminobutyrate transaminase is more sensitive to the vigabatrin drug than the enzyme isolated from bovine brain.

4-Aminobutyrate Transaminase↗
PubMed2000

Detection of hepatitis A viral RNA in sera of patients with acute hepatitis A.

BACKGROUND AND AIMS: The Detection of hepatitis A virus (HAV) is important for diagnosis and epidemiological studies of hepatitis A. The polymerase chain reaction (PCR) technique is a sensitive test to detect HAV-RNA in specimens. The aims of the present study were to clarify the detection rate of serum HAV-RNA by PCR and the natural history of HAV viraemia, and to determine the correlation between viraemia and the clinical characteristics in patients with acute hepatitis A. METHODS: Hepatitis A virus RNA was tested in 74 serum samples which were serially collected from 27 patients with acute hepatitis A. A nested reverse transcription (RT)-PCR for HAV-RNA was performed with primer sets located at the VP1 region of the HAV genome and the PCR products were electrophoresed on a 1.5% agarose gel. RESULTS: Hepatitis A virus RNA was found in 18 of 27 (67%) patients with hepatitis A. There were no significant differences between groups positive and negative for HAV-RNA in clinical and laboratory data, except the time interval between clinical onset and initial serum sampling for RT-PCR (10 +/- 6 vs 19 +/- 14 days) and the alanine aminotransferase (ALT) level at initial serum sampling for RT-PCR (1436 +/- 1416 vs 518 +/- 432 IU/L). The mean duration of HAV viraemia was 30 +/- 19 days (range, 5-59 days). The duration of HAV viraemia and duration of abnormal ALT levels from clinical onset were positively correlated (r = 0.685, P = 0.007). CONCLUSION: In conclusion, HAV-RNA RT-PCR is a useful tool to detect HAV viraemia and to study the molecular epidemiology of HAV infection.

Adult↗
PubMed2000

Cyclo(dehydroala-L-Leu), an alpha-glucosidase inhibitor from Penicillium sp. F70614.

A diketopiperazine (1) has been isolated from the culture broth of Penicillium sp. F70614 and its structure has been determined to be cyclo(dehydroala-L-Leu) by various spectroscopic analyses. This compound selectively inhibited yeast alpha-glucosidase and porcine intestinal alpha-glucosidase with IC50 values of 35 and 50 microg/ml, respectively. However, it did not show significant inhibitory effects against almond beta3-glucosidase, Aspergillus alpha-galactosidase, Escherichia coli beta-galactosidase and jack bean alpha-mannosidase.

Binding, Competitive↗
PubMed1999

Isolation of a psychrotrophic Azospirillum sp. and characterization of its extracellular protease.

A novel psychrotrophic bacterium secreting a protease was isolated from a mountain soil in Korea. On the basis of a 16S rDNA sequence analysis and physiological properties, the isolate was identified as an Azospirillum sp. The protease purified from the culture supernatant was a monomer in its native form with an apparent molecular mass of 48.6 kDa on SDS-PAGE. The protease was active in a broad pH range around 8.5 and at temperatures up to 40 degrees C and stable at temperatures below 30 degrees C for 3 days. The proteolytic activity was inhibited by iodoacetamide and EDTA. The Mg2+ ion did not activate the enzyme much but reversed the inhibition by EDTA, suggesting that the protease belongs to a cysteine protease stabilized by the Mg2+ ion.

Azospirillum↗
PubMed1999

Refolding of pyridoxine-5'-P oxidase assisted by GroEL.

The unfolding of brain pyridoxine-5'-P oxidase by guanidinium chloride has been investigated at equilibrium. Circular dichroism, fluorescence spectroscopy and gel exclusion chromatography were used to monitor the unfolding process. The enzyme dissociates reversibly into monomers, but the fluorescence properties of the cofactor FMN are not restored upon dilution with potassium phosphate buffer (pH 7.4). Spontaneous refolding leads to 20% recovery of the catalytic activity. Addition of GroEL to the renaturing buffer accelerates the recovery of catalytic activity that approaches a level of 80% with respect to the native enzyme. The rate of recovery of catalytic activity assisted by GroEL parallels the rate of FMN fluorescence quenching, suggesting that structural rearrangements of the catalytic domain is the last step to take place in the refolding process.

Animals↗
PubMed1999

Protein-losing enteropathy with an endoscopic feature of 'the watermelon colon'.

A watermelon lesion involving the gastrointestinal tract other than the stomach has not been reported previously except for two cases with rectal involvement and another case with caecal involvement. This report describes a case of protein-losing enteropathy with endoscopic features of 'the watermelon lesion' involving nearly the entire colon. A 57-year-old man presented with a six-month history of generalized oedema and diarrhoea. Laboratory findings included elevated erythrocyte sedimentation rate and decreased serum total protein and albumin. Serum fluorescent anti-nuclear antibody, anti-dsDNA antibody and anti-La antibody were positive. Upper gastrointestinal endoscopy was unremarkable. Colonoscopy showed seven or eight longitudinal reddish stripes along the entire length of the colon and rectum sparing the caecum. Biopsies from the duodenum and colon revealed mildly ectatic lymphatics in the submucosa. Colonic biopsy also exhibited some haemosiderin-laden macrophages in the muscularis mucosae and submucosa. 99mTc-human serum albumin scintigraphy demonstrated a leak into the intestinal lumen. Oral prednisolone therapy was started and his symptoms and signs gradually improved over months. Steroid could be withdrawn after 7 months of therapy, and the patient has remained free of symptoms for 1 year of follow-up after withdrawal of the steroid.

Anti-Inflammatory Agents↗
PubMed1998

Quantitative analysis of free sphingoid bases in the brain and spinal cord tissues by high-performance liquid chromatography with a fluorescence detection.

The o-phthaldialdehyde precolumn derivatives of psychosine, sphinganine and sphingosine extracted from brain and spinal cord tissues were determined by high-performance liquid chromatography-fluorescence detection. This method was developed with the purpose of detecting an endogenous amount of psychosine, sphingosine and sphinganine using small aliquots of brain tissues and spinal cord in rats. These sphingolipid bases were extracted in various ratios of chloroform-methanol and several pH values. Recovery of the method is about 81% in 12 ng/tube (final volume, 320 microl), 90-95% in 45 ng/tube of sphingosine and sphinganine within 2-12% relative standard deviation. Detection limits of these sphingoid bases were about 0.05 pmol/mg brain tissue. In the forebrain, brainstem and spinal cord of rats at three different ages of postnatal days (PND) 1, PND 13 and 6 months old, the endogenous concentrations of psychosine, sphingosine and sphinganine were determined. From these results, this method is suitable for the determination of sphingoid bases in small aliquot of brain and spinal cord tissues.

Aging↗
PubMed1998

Pharmacokinetics of propentofylline and the quantitation of its metabolite hydroxypropentofylline in human volunteers.

Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been reported to be effective for the treatment of both vascular dementia and dementia of the Alzheimer type. The pharmacological effects of PPF may be exerted via the stimulation of nerve growth factor, increased cerebral blood flow, and inhibition of adenosine uptake. The objectives of this experiment are to determine the kinetic behavior of PPF, to identify, and to quantify its metabolite in human. Blood samples were obtained from human volunteers following oral administration of 200 mg of PPF tablets. For the identification and quantification of the metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine (PPFOH), PPFOH was synthesized and identified by gas chromatography/mass spectroscopy (GC/MS) and 1H-nuclear magnetic resonance spectroscopy. The molecular weight of synthesized metabolite is 308 dalton. The PPF and PPFOH in plasma were extracted with diethyl ether and identified by electron impact GC/MS. The plasma concentrations of PPF and PPFOH were determined by gas chromatography/nitrogen phosphorus detector in plasma and their pharmacokinetic parameters were determined. The mean half-life of PPF was 0.74 hr. The areas under the curve (AUCs) of PPF and PPFOH were 508 and 460 ng.hr/ml, respectively. Cmax of PPF was about 828.4 ng/ml and the peak concentration was achieved at about 2.2 hr (Tmax). These results indicate that PPF is rapidly disappeared from blood due to extensive metabolism into PPFOH.

Administration, Oral↗
PubMed1998

Apoptosis in the pathogenesis of cutaneous lupus erythematosus.

Defective regulation of apoptosis may play a role in the development of autoimmune diseases such as systemic lupus erythematosus, in which the skin is a prominent target. To our knowledge, however, the nature of epidermal changes in cutaneous lupus erythematosus (LE) has not previously been investigated. We investigated the involvement of apoptosis in cutaneous LE. A total of 44 lesional skin samples from patients with cutaneous LE, 44 skin samples from patients with scleroderma, five skin specimens from patients suffering from dermatomyositis, and 13 normal skin samples were stained immunohistochemically with monoclonal antibodies to Ki-67, p53 (DO-7), and bcl-2. The lesional skin from cutaneous LE, except LE profundus, showed a marked increase in Ki-67- and p53-positive keratinocytes, which were predominantly located in the basal layer of the epidermis and follicle, and a drastic reduction in the number of bcl-2-positive cells localized in the basal cell compartment. With TdT-mediated dUTP-biotin nick end-labeling staining, we demonstrated that extensive apoptosis occurred in almost the whole epidermis of cutaneous LE, except in cases of LE profundus. This abnormal expression of Ki-67, p53, and bcl-2 and the occurrence of apoptosis in the epidermis was also observed in epidermis from patients with dermatomyositis, but not in that from patients with scleroderma.

Apoptosis↗
PubMed1998

Endoscopic treatment in a case with extensive spontaneous intramural dissection of the oesophagus.

Spontaneous intramural dissection of the oesophagus has been recognized as a separate clinical entity between a transmural oesophageal rupture (Boerhaave syndrome) and an oesophageal mucosal tear (Mallory-Weiss syndrome). It is important to differentiate this condition from myocardiac infarction, dissecting aneurysm and other acute surgical conditions. Conservative management is usually thought to be adequate. We report a case of spontaneous intramural oesophageal dissection, in which the symptom of dysphagia did not improve with the conservative management and an endoscopic incision of the septum between true and false lumens using a needle-type diathermy knife was done safely and effectively.

Endoscopy↗
PubMed1997

Human oral buccal mucosa reconstructed on dermal substrates: a model for oral epithelial differentiation.

To develop a model for the study of oral epithelial differentiation, we reconstructed artificial buccal mucosa equivalents using keratinocytes and fibroblasts or de-epidermized dermis derived from non-cornifying buccal mucosa. The buccal mucosa equivalents reconstructed in this way showed a morphology closely mimicking that of their in vivo counterparts. There was no formation of horny layers and granular layers. The expression of various differentiation markers such as K13, involucrin and loricrin was consistent with that of the in vivo state, and indicative of the hyperproliferative state. We also demonstrated that the differentiation of oral epithelial cells was influenced by the de-epidermized dermis and subepithelial fibroblasts. The epidermis of buccal mucosa equivalents seemed to be less sensitive to retinoic acid than that of the skin. The effects of calcipotriol on the buccal mucosa equivalent and the skin epidermis were different. These results suggest that the pharmacological effects of retinoic acid and calcipotriol on the buccal mucosa are different from those on the skin. A useful model system for studies of oral keratinocyte differentiation and pharmacological research could be based on these artificial buccal mucosa equivalents.

Calcitriol↗
PubMed1997

Regulations of collagen synthesis by ascorbic acid, transforming growth factor-beta and interferon-gamma in human dermal fibroblasts cultured in three-dimensional collagen gel are photoaging- and aging-independent.

Decreased collagen synthesis and loss of responsiveness to growth factors are well known phenomena in in vivo or in vitro aged cells. Ascorbic acid and some cytokines such as transforming growth factor-beta and interferon-gamma are important regulators of collagen synthesis. To investigate the responsiveness of fibroblasts with regard to the photoaging and aging process, we examined the effect of ascorbic acid, TGF-beta, and IFN-gamma on collagen synthesis in dermal fibroblasts from three newborn foreskins (1 day old) and in both exposed and unexposed skin fibroblasts from 4 old individuals (60-76 years old) cultured in monolayer and in collagen gel. We demonstrated that basal levels of collagen synthesis decreased with increasing age. Photoaged fibroblasts in collagen gel showed greater basal collagen synthesis than aged fibroblasts in the same individuals, but similar basal collagen synthesis in monolayer cultures. Even though basal levels of collagen synthesis in collagen gel are downregulated in a photoaging- and aging-dependent manner, collagen synthesis by ascorbic acid in collagen gel, and by TGF-beta and IFN-gamma in both monolayer culture and collagen gel were regulated in a photoaging- and aging-independent manner. In monolayer culture, however, the responsiveness to ascorbic acid in newborn fibroblasts was greater than in photoaged and aged fibroblasts. Our results suggest that there are differences in collagen synthesis between photoaged and aged cells, depending on culture conditions. Responsiveness to ascorbic acid, TGF-beta and IFN-gamma related to collagen synthesis in photoaged and aged fibroblasts in collagen gel appears to be the same as in newborn fibroblasts, even though basal levels of collagen synthesis are downregulated in a photoaging- or aging-dependent manner.

Aged↗
PubMed1997

Binding of the activating ion Co(II) to myo-inositol monophosphatase monitored by fluorescence and phosphorescence spectroscopy.

Two extrinsic probes, pyrene-maleimide and eosin-maleimide, were used to label specific SH groups of the enzyme myo-inositol monophosphatase. The fluorescence of pyrene-monophosphatase is enhanced upon addition of the activating metal ions Co(II) and Mg(II). Co(II) ions bind with a dissociation constant of 4 microM, whereas the apparent activation constant Ka is 0.4 mM. Energy transfer measurements demonstrated that the pyrene chromophore, covalently linked to Cys-218, is within 9 A of the metal ion Tb(III) coordinated to the metal-binding site. The phosphorescence emitted by eosin covalently linked to the protein is quenched by the addition of the activating cations Co(II) and Mg(II). Phosphorescence titrations conducted under anaerobic conditions were used to determine a dissociation constant of approximately 3 microM for the binding of Co(II) ions. The results are consistent with the hypothesis that two activating ions per monomeric subunit participate in the catalytic mechanism. The affinity of the tightly bound ion is at least 100-fold greater than the affinity of the weakly bound ion.

Animals↗
PubMed1997

Primary cutaneous Langerhans cell histiocytosis treated with photochemotherapy.

A 23-year-old man with Langerhans cell histiocytosis presented with asymptomatic, purplish, slightly scaly, confluent papules of one year's duration. Histological studies of biopsy specimens revealed a dense infiltrate of histiocytic mononuclear cells beneath the epidermis; these cells reacted strongly with anti-S-100 antibodies. Extensive investigations failed to detect systemic involvement. He was treated with repeated oral 8-methoxypsoralen (8-MOP) plus ultraviolet A (PUVA) therapy three times a week for two months and then once or twice with maintenance phototherapy. The lesions did not recur during the four-month follow-up period.

Administration, Oral↗
PubMed1997

Prenatal fumonisin (FB1) treatment in rats results in minimal maternal or offspring toxicity.

To investigate the neurobehavioral and developmental effects of the mycotoxin, FB1, Sprague-Dawley rats were treated with FB1 on gestational days 13-20. In Experiment 1, FB1 was obtained from culture material and pregnant rats were gavaged with 0, 0.8 or 1.6 mg/kg. In Experiment 2, pregnant rats were gavaged with purified FB1 at doses of 0, 1.6 or 9.6 mg/kg. Offspring were evaluated on a battery of behavioral tests as well as measures of whole and regional brain weight. There were no effects on maternal weight gain, reproductive outcomes, or offspring body weight through adulthood in either experiment. Complex maze performance, open field and running wheel activity were not altered by prenatal FB1 treatment. In Experiment 2, acoustic startle response was depressed at two ages during the first or second block of 9 trials in males treated with purified FB1. Females exhibited no such alterations. Play behavior at PND 33, but not PND 26, was increased in males prenatally treated with 9.6 mg/kg relative to those treated with 1.6 mg/kg. There were no substantive treatment effects on regional brain weight. These results suggest that doses of < or = 9.6 mg purified FB1/kg and/or < or = 1.6 mg FB1/kg obtained from culture material cause minimal maternal toxicity and produce few development functional alterations. In addition, potential FB1-related functional alterations were evident only in males providing further support for a mild sex-specific effect for fumonisin.

Animals↗