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Biomedical subjects

D H Kim

Publications and source records attributed to D H Kim.

At least 127 records · Page 7Linked to original sources
PubMed2001

Metabolism of chiisanoside from Acanthopanax divaricatus var. albeofructus by human intestinal bacteria and its relation to some biological activities.

The metabolic pathway of chiisanoside isolated from leaves of Acanthopanax divaricatus var. albeofructus (Araliaceae) by human intestinal bacteria and by the protein fraction of leaves of this plant were investigated, and the cytotoxic and anti-rotaviral activities of chiisanoside and its metabolite, chiisanogenin, were assayed. Chiisanogenin was produced as a main metabolite, when chiisanoside were incubated for 15 h with human intestinal bacteria. This metabolic pathway proceeded more potently with the protein fraction than with human intestinal bacteria. The in vitro cytotoxicity of chiisanogenin was superior to that of chiisanoside. H+/K+ ATPase was more potently inhibited by chiisanogenin than by chiisanoside. However, the anti-rotaviral activity of chiisanoside was more potent than that of chiisanogenin.

Animals↗
PubMed2001

Purification and characterization of ginsenoside Rb1-metabolizing beta-glucosidase from Fusobacterium K-60, a human intestinal anaerobic bacterium.

Fusobacterium K-60, a ginsenoside Rb1-metabolizing bacterium, was isolated from human intestinal feces. From this Fusodobacterium K-60, a ginsenoside Rb1-metabolizing enzyme, beta-glucosidase, has been purified. The enzyme was purified to apparent homogeneity by a combination of butyl-Toyopearl, hydroxyapatite ultragel, Q-Sepharose, and Sephacryl S-300 HR column chromatographies with a final specific activity of 1.52 micromol/min/mg. It had optimal activity at pH 7.0 and 40 degrees C. The molecular mass of this purified enzyme was 320 kDa, with 4 identical subunits (80 kDa). The purified enzyme activity was inhibited by Ba++, Fe++, and some agents that modify cysteine residues. This enzyme strongly hydrolyzed sophorose, followed by p-nitrophenyl beta-D-glucopyranoside, esculin, and ginsenoside Rb1. However, this enzyme did not change 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (IH-901) to 20(S)-protopanaxadiol, while it weakly changed ginsenoside Rb1 to IH-901. These findings suggest that the Fusobacterial beta-glucosidase is a novel enzyme transforming ginsenoside Rb1.

Fusobacterium↗
PubMed2001

Serum leptin, IGF-I and insulin levels in preterm infants receiving parenteral nutrition during the first week of life.

Leptin is involved in the regulation of body weight through a feedback signal between adipose tissue and the satiety center, to decrease food intake and increase energy expenditure. Newborn infants experience physiological weight loss during the first week of life. The leptin level may be decreased to enhance food intake and to decrease energy expenditure for physiological adaptation during early postnatal days. Insulin-like growth factor-I (IGF-I) and insulin are involved in the regulation of perinatal growth. Leptin might be interrelated with IGF-I or insulin, since both of these have adipogenic and somatotropic effects. We therefore hypothesized that leptin, IGF-I and insulin would be decreased during the first week of life, concurrently with physiological weight loss. Thirty preterm AGA infants (birth weight 1.574+/-313 g; GA 31.9+/-2.2 wk) were studied. All infants received parenteral nutrition from the third day after birth. Leptin was significantly decreased during the first week of life, and insulin was significantly increased at day 7 vs. day 1 and day 3. IGF-I did not change during the first week of life. Leptin was positively correlated with body weight (r = 0.368, p<0.01), body mass index (r = 0.267, p<0.05), and serum IGF-I (r = 0.330, p <0.01), but not with serum insulin. The percent of weight reduction during the first week of life was not correlated with the percent of leptin reduction during the first week of life. In conclusion, leptin was significantly decreased and positively correlated with body weight and IGF-I during the first week of life. Changes of leptin and insulin might be related to postnatal adaptation in metabolism, but the exact role of leptin, IGF-I and insulin in postnatal physiological weight loss is not clear.

Aging↗
PubMed2001

Mechanism-based inhibition of zinc proteases.

The functions of zinc proteases have been implicated in a host of physiological and pathological processes in living organisms. Mechanism-based inhibitors are highly sought as biologically active molecules that afford high selectivity in targeting specific enzymes. Mechanism-based inhibitors for zinc-dependent proteases have been developed in the past several years. These inhibitors exploit the chemistry inherent to transition metals in their mechanisms of enzyme inhibition. These efforts have been reviewed in this manuscript.

Animals↗
PubMed2001

Origin of chiral pharmacology: stereochemistry in metalloprotease inhibition.

The stereospecificity shown by a wide variety of inhibitors that are effective for carboxypeptidase A (CPA), a representative zinc protease is analyzed on the basis of inhibitor type. In cases of ground state analog inhibitors and transition state analog inhibitors, the stereoisomers having the stereochemistry that corresponds to stereochemistry of substrate are more potent, but in the case of irreversible inhibitors including mechanism-based inactivators the preferred inhibitory stereochemistry cannot be predicted simply from the substrate stereospecificity. The Ogston's three point fit concept may be of great value in understanding the inhibitory stereochemistry of reversible competitive inhibitors. On the other hand, the stereochemistry of irreversible inhibitors may possibly be predicted on the ground of the transition state structure that plays a critical role in the inactivation pathway.

Binding Sites↗
PubMed2001

Surgical management and outcome in patients with radial nerve lesions.

OBJECT: The goal of this paper was to review surgical management and outcomes in patients treated for radial nerve (RN) lesions at Louisiana State University Health Sciences over a period of 30 years. METHODS: Two hundred sixty patients with RN injuries were evaluated. The most common mechanisms of injuries involving the RN included fracture of the humerus, laceration, blunt contusions, and gunshot wounds. One hundred and eighty patients (69%) underwent surgery. Lesions not in continuity required primary or secondary end-to-end suture repairs or graft repairs. With the use of direct intraoperative nerve action potential recording, RN injuries in which the lesion was in continuity required external or internal neurolysis or resection of the lesion followed by end-to-end suture or graft repair. A minimum of 1.5 years follow-up review was available in 90% of the patients who underwent surgery. Motor function recovery to Grade 3 or better was observed in 10 (91%) of 11 patients who underwent primary suture repair, 25 (83%) of 30 who underwent secondary suture repair, 43 (80%) of 54 who received graft repair, and 63 (98%) of 64 in whom neurolysis was performed. Sixteen (71%) of 21 patients with superficial sensory RN injury achieved satisfactory pain relief after complete resection of a neuroma or neurolysis. CONCLUSIONS: This study clearly demonstrates that excellent functional recovery can be achieved with proper surgical management of RN injuries.

Adolescent↗
PubMed2001

Surgical management and outcomes in patients with median nerve lesions.

OBJECT: One hundred sixty-seven of 250 patients with median nerve (MN) lesions, excluding carpal tunnel syndrome and nerve sheath tumors, at the levels of the arm, elbow, forearm, and wrist, underwent surgical treatment at Louisiana State University Health Sciences over a 30-year period. The most common causes of MN injuries were laceration, fracture-associated stretch and contusion, gunshot wound, compression, and injection injuries. In this study, surgically treated patients were followed and evaluated retrospectively for favorable functional outcomes. METHODS: Lesions not in continuity required primary or secondary end-to-end suture or graft repairs. With the aid of direct intraoperative recording of nerve action potentials (NAPs), MN injuries in which the lesion was in continuity underwent external or internal neurolysis, or resection of the lesion, followed by end-to-end suture or graft repair. A minimum of 12 months follow-up review (mean 18 months) was available in 85% of the surgically treated patients. For lesions in continuity, a functional recovery of Grade 3 or better was seen in 72 (95%) of 76 patients who underwent neurolysis, 18 (86%) of 21 who received suture repair, and 21 (75%) of 28 who received graft repair. In lesions not in continuity, favorable results (Grade > or = 3) were seen in 10 (91%) of 11 patients who received primary suture repair, seven (78%) of nine who received secondary suture repair, and 15 (68%) of 22 who received graft repair. CONCLUSIONS: Surgical intervention for MN injuries with complete or severe deficits achieved favorable outcomes.

Adolescent↗
PubMed2001

Gastric lymphangioma.

Gastric lymphangioma is a rare benign gastric tumor composed of unilocular or multilocular lymphatic spaces. On gastrofiberscopy a submucosal tumor covered with smooth transparent normal mucosa is revealed in the stomach with or without a stalk. Endoscopic ultrasonography has become an indispensable tool for differentiating these gastric tumors. Treatment of lymphangioma depends on its size, location, and presence of complications. Endoscopic resection is safe and easy and plays an important role in confirming the diagnosis and treatment of the tumors especially of small-sized ones. We report a case of gastric lymphangioma in a 68-yr-old woman who presented with nausea and vague epigastric discomfort for two months. She was diagnosed by gastrofiberscopy with endoscopic ultrasonography and treated successfully with endoscopic resection by strip biopsy method.

Aged↗
PubMed2001

Metabolism of dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) by human liver microsomes: characterization of metabolic pathways and of cytochrome P450 isoforms involved.

Metabolic fate of DDB and identification of P450 isozymes involved in the metabolism of DDB were investigated in human liver microsomes. DDB was rapidly metabolized to five different metabolites, and the structures of each metabolite were characterized based on UV, mass, and NMR spectral analyses. The major metabolic pathways of DDB in human liver microsomes were identified as O-demethylation of the carboxymethyl moiety (M4) and demethylenation of the methylenedioxyphenyl group (M2). The intramolecular lactonization between the hydroxyl group at the C6 and carboxymethyl group at the C2' of M2 resulted in the generation of M5, which was either hydrolyzed to its hydrolyzed derivative (M1) or further metabolized to the O-demethylated derivative (M3). The interconversion of M1, M2, and M5 took place nonenzymatically depending on the solvent condition. M5 was predominantly detected at the acidic condition, whereas M1 was preferentially detected at the basic environment. Cytochrome P450 (P450) isoform(s) involved in the metabolism of DDB was identified using several in vitro approaches. Chemical inhibition using isoform-selective P450 inhibitors, correlation of DDB metabolites formation with several isoform-specific P450 activities in a panel of liver microsomes, metabolism by microsomes derived from P450 cDNA-expressed B-lymphoblastoid cells, and immunoinhibition by isoform-specific anti-P450 antibodies collectively indicated that CYP1A2, CYP2C9, and CYP3A4 are responsible for the metabolism of DDB. O-Dealkylation of the carboxymethyl group was preferentially catalyzed by CYP1A2, whereas demethylenation of the methylenedioxyphenyl moiety was catalyzed by CYP3A4 and CYP2C9.

Antibodies↗
PubMed2001

Tissue-engineered pancreatic islets: culturing rat islets in the chitosan sponge.

Subcutaneous islet transplantation has become an attractive modality. With development of tissue-engineering techniques, it is possible to rectify the disadvantage of poor blood supply in the subcutaneous site by reconstruction of the capillary network. According to reports, the Chitosan sponge (CS) could be used for reconstruction of in vitro capillary-like network and could be used in artificial skin equivalent. In this study, we cultured the islets in CS for future application. CSs, having 200-500 microm pore size, were prepared by freeze-drying method. Rat islets were isolated from the pancreas of Lewis rats (10 weeks old, 280-300 g, male) by collagenase digestion followed by discontinuous dextran gradient centrifugation method. Each 20 islets were seeded equally into the CSs and were cultured for 62 days with various culture media such as RPMI-1640, Dulbecco's modified Eagle's medium (DMEM), and Eagle's MEM. They contained 10% fetal bovine serum (FBS) and 5 ml/L antibiotic-antimycotic mixed stock solution in the culture dishes. Insulin concentration both inside and outside of the islet-seeded CS was measured during culture. Changes in the morphology of islets were also observed in this study. Freshly isolated islets had a loose appearance with an irregular border, and most were seen as a single islet. Occasionally a cluster, consisting of 2-4 islets ranging mainly from 150 to 250 microm in diameter, was observed. Islets cultured in the CSs in different culture media retained initial morphology, which had well-delineated smooth borders for at least 53 days. The insulin release behavior of islets cultured in the CS showed constant secretory capacities for 49 days. After that they exhibited a rapid and definitive decline from the initial insulin release. Until this stage, insulin concentration in the CS was well maintained. The properties were dependent on culture medium used and insulin diffusion released from islets. This experiment is a new study model for establishment of islet culture in a three-dimensional matrix. Also extension of this observation will provide new insights for islet transplantation at the subcutaneous site by a tissue-engineering approach.

Animals↗
PubMed2001

Characterization of the selectivity and mechanism of cytochrome P450 inhibition by dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'-dicarboxylate.

In vitro studies with human liver microsomes and cytochrome P450 (P450) prototype substrates were performed to characterize the selectivity and mechanism of inhibition of P450 by dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'-dicarboxylate (DDB). DDB was found to be a strong inhibitor of testosterone 6beta-hydroxylation activity (CYP3A4) with a K(i) value of 0.27 +/- 0.21 microM. At higher concentrations, DDB marginally inhibited caffeine N(3)-demethylation (CYP1A2), diclofenac 4'-hydroxylation (CYP2C9), and dextromethorphan O-demethylation (CYP2D6) activities, but this compound had no effect on CYP2A6-, CYP2C19-, and CYP2E1-mediated reactions. Spectral analysis indicated that the formation of metabolite-P450 complex having absorbance at 456 nm was concentration-dependent; 5 to 33% of the total P450 was complexed in rat and human liver microsomes after a 5-min incubation with DDB. In addition, microsomal incubations with DDB in the presence of NADPH resulted in a loss of spectral P450 content, which was restored after adding K(3)Fe(CN)(6). This complex formation resulted in a time-dependent loss of CYP3A-catalyzed marker activity (testosterone 6beta-hydroxylation) in human liver microsomes. The inhibition was only partially restored upon dialysis. These results collectively suggest that formation of a metabolite-CYP3A complex with DDB was responsible for the CYP3A-selective time-dependent loss of catalytic function of CYP3A.

Animals↗
PubMed2000

Flow cytometric analysis and chromosome sorting of barley (hordeum vulgare L).

Flow cytometric analysis was systematically performed to optimize the concentration and duration of hydroxyurea (DNA synthesis inhibitor) and trifluralin (metaphase blocking reagent) treatments for synchronizing the cell cycle and accumulating metaphase chromosomes in barley root tips. A high metaphase index (76.5% in the root tip meristematic area) was routinely achieved. Seedlings of about 1.0-cm length were treated with 1.25 mM hydroxyurea for 14 h to synchronize the root tip meristem cells at the S/G2 phase. After rinsing with hydroxyurea, the seedlings were incubated in a hydroxyurea-free solution for 2 h and were treated with 1 microM trifluralin for 4 h to accumulate mitotic cells in the metaphase. The consistent high metaphase index depended on the uniform germination of seeds prior to treatment. High-quality and high-quantity isolated metaphase chromosomes were suitable for flow cytometric analysis and sorting. Flow karyotypes of barley chromosomes were established via univariate and bivariate analysis. A variation of flow karyotypes was detected among barley lines. Two single chromosome types were identified and sorted. Bivariate analysis showed no variation among barley individual chromosomes in AT and GC content.

Analysis of Variance↗
PubMed2000

The asp-rich region at the carboxyl-terminus of calsequestrin binds to Ca(2+) and interacts with triadin.

Calsequestrin (CSQ) is a high capacity Ca(2+) binding protein in the junctional sarcoplasmic reticulum of striated muscles, and has been shown to regulate the ryanodine receptor (RyR) through triadin and junctin. In order to identify the functional roles of specific regions on CSQ, several CSQ deletion mutants were prepared by molecular cloning and Escherichia coli expression. 45Ca(2+) overlay assay using a native gel system revealed that the major Ca(2+) binding motif of CSQ resides in the asp-rich region (amino acids 354-367). In an in vitro binding assay using a glutathione-S-transferase affinity column, the interaction between CSQ and triadin was found to be Ca(2+)-dependent, and the site of interaction was confined to the asp-rich region of CSQ. Our results suggest that the asp-rich region of CSQ could participate in the RyR-mediated Ca(2+) release process by offering a direct binding site to luminal Ca(2+) as well as triadin.

Animals↗
PubMed2000

Increased plasma corticosterone, aggressiveness and brain monoamine changes induced by central injection of pertussis toxin.

The effects of intracerebroventricular (i.c.v.) injection of pertussis toxin, a specific inhibitor of G(i)/G(o) proteins, on plasma corticosterone levels, aggressiveness, and hypothalamic and hippocampal monoamines and their metabolites levels were examined in mice. Plasma corticosterone level was markedly increased at 3 h after pertussis toxin injection (0.03 and 0.2 microg/mouse), peaked at 6 h and was still increased for up to 6 days after injection. Mice injected with pertussis toxin (0.2 microg/mouse) did not show weight gain between day 0 and day 6 after injection. In addition, pertussis toxin (0.2 microg/mouse) induced a progressive increase in aggressiveness, i.e. a decrease in attack latency and an increase in number of attacks, on day 1 and 6 after injection. Brain monoamines and their metabolites levels were changed on day 1 and 6 after pertussis toxin injection (0.2 microg/mouse): in the hypothalamus, levels of dopamine and 3,4-dihydroxyphenylacetic acid were increased, norepinephrine level decreased, and 5-hydroxyindole acetic acid (5-HIAA) level was markedly increased, with no changes in 5-hydroxytryptamine (5-HT) level, whereas in the hippocampus, 5-HT level was significantly decreased, with no changes in 5-HIAA and catecholamines. These results suggest that signal transduction through G(i)/G(o) proteins in the brain is involved in the modulation of hypothalamo-pituitary-adrenal axis, aggressiveness, and monoamine levels in vivo.

Aggression↗
PubMed2000

Development of spontaneous hyperplastic skin lesions and chemically induced skin papillomas in transgenic mice expressing human papillomavirus type 16 E6/E7 genes.

Human papillomavirus type 16 (HPV16) has been known to be the major factor for the development of uterine cervical carcinomas. We have developed a line of transgenic mice that express the HPV16 E6 and E7 genes in certain organs using a fusion gene which consists of the tyrosinase promoter and E6/E7 of HPV16, and have chosen the tyrosinase minigene as a co-injected visual marker for the identification of transgenic mice. Our transgenic mice (1) expressed E6/E7 transgene mainly in skin and heart, and (2) showed skin and eye pigmentation profiles, and (3) raised incidence of hyperplastic skin lesions. We had performed two-stage skin carcinogenesis experiment to detect the susceptibility of skin papilloma development in our transgenic mice, using dimethylbenz-anthracene (DMBA) as a initiating agent and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). After 1 week of DMBA treatment (25 microg dissolved in 0.2 ml acetone) and 15 consecutive weeks of TPA treatment (2.5 microg dissolved in 0.2 ml acetone) on the back of transgenic and non-transgenic control mice (Fv-1(b) strain mice which are Friend virus B-type susceptible (FVB)/N), papilloma incidence was increased in our transgenic mice approximately 2-fold higher than in control (in female mice, 69.2 vs. 30%, respectively). Thus our transgenic mice may be useful for the development of immunological or other therapies for HPV-associated cancers.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Calcineurin regulates ryanodine receptor/Ca(2+)-release channels in rat heart.

The present study was undertaken to examine the physical and physiological interaction of protein phosphatase 2B, calcineurin, with the ryanodine receptor (RyR) in rat cardiac tissue and neonatal cardiomyocytes. The presence of calcineurin, the RyR and FK506-binding protein (FKBP)12.6 in rat cardiac sarcoplasmic reticulum (SR) was identified by Western blot analysis. The possible interactions between calcineurin, the RyR and FKBP12.6 were further studied by co-immunoprecipitation using CHAPS-solubilized cardiac-membrane fractions (CSMFs) or SR preparations. Physical interactions between the RyR and calcineurin were found in the CSMF in the presence of added 100 microM Ca(2+); however, the interactions were interrupted in the presence of 20 mM EGTA, 1 microM rapamycin or 1 microM FK506, suggesting that the interaction is Ca(2+)-dependent, and is mediated by FKBP12.6. The Ca(2+)-dependent interaction between FKBP12.6 and the RyR was also found by co-immunoprecipitation. Effects of calcineurin inhibitors were tested on neonatal-rat-heart cardiomyocytes. Treatment of neonatal cardiomyocytes with 20 microM deltamethrin, 10 microM cyclosporin A (CsA), or 10 mciroM FK506 led to Ca(2+) oscillations in originally quiescent cardiomyocytes. Preincubation of cardiomyocytes with 20 microM rapamycin which dissociates FKBP12.6 from the RyR, evoked Ca(2+) oscillations, probably due to the leakiness of the RyR. However, Ca(2+) oscillations by rapamycin were not further affected by 10 microM CsA or 10 mciroM deltamethrin, suggesting that only RyR-associated calcineurin could regulate the channel activities. In spontaneously Ca(2+)-oscillating cardiomyocytes, CsA or FK506 treatments increased the frequency of oscillations. In 10 microM ryanodine-treated cardiomyocytes, CsA failed to induce Ca(2+) oscillations. These data show evidence that calcineurin associated with the RyR could modulate Ca(2+) release in rat heart.

Animals↗