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Biomedical subjects

Y B Kim

Publications and source records attributed to Y B Kim.

At least 19 recordsLinked to original sources
PubMed2001

Biosynthesis of polyhydroxyalkanoate copolyester containing cyclohexyl groups by Pseudomonas oleovorans.

Production of polyhydroxyalkanoates (PHAs) substituted with cyclohexyl groups by Pseudomonas oleovorans grown with 4-cyclohexylbutyric acid (4-CHB) and its mixtures with nonanoic acid (NA) was investigated. Addition of NA to medium gave rise to an increase in the total concentration of 3-hydroxy-4-cyclohexylbutyrate repeating unit in the PHAs, indicating that the bioconversion rate of 4-CHB to polyester was significantly improved by the cometabolic effect. Increasing the proportion of NA from 1.0 to 7.5 mM at a concentration of 10 mM total carbon substrate also accelerated the uptake speed of 4-CHB by the organism and resulted in an increase of the ratio of 3-hydroxynonanoate to 3-hydroxyheptanoate from 1.28 to 2.05. Differential scanning calorimetric analysis of the PHAs bearing the corresponding functional groups showed one melting transition and one glass transition temperature varying according to the composition. These results indicated that random copolyesters were obtained from the carbon substrates used in this study.

Butyric Acid↗
PubMed2001

Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett's esophagus: clue for the chemoprevention of esophageal carcinoma by antioxidants.

Oxidative damage has long been related to mucosal damages of gastrointestinal tracts and their ensuing carcinogenesis. In spite of treatment with anti-secretory medications for reflux esophagitis, considerable portions of patient did not achieve the complete mucosal healings or suffered from sustaining symptoms or development of dread complication like Barrett's esophagus, suggesting other damaging factors or impaired mucosal resistance are also involved in their pathogenesis. The present study was designed either to evaluate the oxidative stress as the major pathogenic factor of reflux esophagitis or to find out the usefulness of antioxidant in the treatment of reflux esophagitis and the prevention of development of Barrett's esophagus. Acute or chronic reflux esophagitis was induced through either narrowing the third portion of duodenal lumen or performing myotomy of lower esophageal sphincter in rats, respectively. DA-9601, a new phytopharmaceutical possessing antioxidative properties, significantly attenuated the gross and histopathologic scores of acute reflux esophagitis in a dose-dependent manner compared to those treated with ranitidine alone. Only scattered erosions were observed in antioxidant pre-treated group, but acid suppression by ranitidine was not so effective in decreasing the severity of reflux esophagitis. Significantly increased amounts of malondialdehyde (MDA), increased NF-kappa B activations, and depletions of reduced glutathione (GSH) were observed in experimentally induced reflux esophagitis, but DA-9601 pre-treatment attenuated the decrement of mucosal GSH levels and decreased MDA formations significantly. DA-9601 treatment showed significant reductions in the activation of NF-kappa B transcription factor. DA-9601 significantly decreased the proliferating cell nuclear antigen-labeling index (PCNA-LI) of esophagus (P<0.05) in chronic reflux esophagitis model and prevented the development of Barrett's esophagus. In conclusion, reflux esophagitis provoked considerable levels of oxidative stress in the esophageal mucosa. Antioxidant treatment seems to be the first line therapeutics in the prevention or treatment of reflux esophagitis. Moreover, antioxidant possibly played the chemopreventive role through preventing the development of Barrett's esophagus.

Acute Disease↗
PubMed2001

Restriction fragment length dimorphism-PCR method for the detection of extended-spectrum beta-lactamases unrelated to TEM- and SHV-types.

The diagnostic ability of the restriction fragment length dimorphism-polymerase chain reaction (RFLD-PCR) method was evaluated. Seven primer pairs, newly designed from 44 beta-lactamase genes encoding extended-spectrum beta-lactamases not related to TEM- and SHV-types, were used to differentiate OXA-2, FOX-3, CMY-3, IMP-1, and IMI-1 beta-lactamases. The RFLD-PCR was carried out successfully, and these genes were differentiated by the sizes of their PCR products and by the difference in restriction fragment length when each amplicon was digested with a unique restriction enzyme. This discriminatory detection of the genes was confirmed by sequencing the PCR products.

Bacterial Proteins↗
PubMed2001

Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes.

beta cells sense glucose through its metabolism and the resulting increase in ATP, which subsequently stimulates insulin secretion. Uncoupling protein-2 (UCP2) mediates mitochondrial proton leak, decreasing ATP production. In the present study, we assessed UCP2's role in regulating insulin secretion. UCP2-deficient mice had higher islet ATP levels and increased glucose-stimulated insulin secretion, establishing that UCP2 negatively regulates insulin secretion. Of pathophysiologic significance, UCP2 was markedly upregulated in islets of ob/ob mice, a model of obesity-induced diabetes. Importantly, ob/ob mice lacking UCP2 had restored first-phase insulin secretion, increased serum insulin levels, and greatly decreased levels of glycemia. These results establish UCP2 as a key component of beta cell glucose sensing, and as a critical link between obesity, beta cell dysfunction, and type 2 diabetes.

Adenosine Triphosphate↗
PubMed2001

The significance of granzyme B expression in patients with angiocentric lymphoma of the head and neck.

BACKGROUND: The objectives of this study were to establish a correlation between granzyme B expression and the clinicopathologic characteristics of patients with angiocentric lymphomas of the head and neck and to determine whether the expression of granzyme B had any influence on the treatment outcomes of such patients. METHODS: Fifty-seven patients with angiocentric lymphoma of the head and neck who were treated between 1987 and 1996 were divided into two groups according to whether their tumors were immunoreactive for granzyme B: the granzyme B negative group (n = 22 patients) and the granzyme B positive group (n = 35 patients). The clinicopathologic features, immunohistochemical findings, patterns of disease failure, and survival data for the granzyme B positive group were compared with those for the granzyme B negative group. RESULTS: Greater than 60% of patients with angiocentric lymphoma of the head and neck were shown to have granzyme B positive tumors. All tumors that expressed granzyme B also consistently coexpressed CD56, indicating that they probably are the neoplastic equivalent of either natural killer (NK) cells or activated cytotoxic T cells. Although there were no significant differences in histopathologic features or expression of CD45RO and polyclonal CD3-epsilon between the groups, the Epstein-Barr virus genomes were detected more frequently in the granzyme B positive group compared with the granzyme B negative group. Despite a similar rate of complete remission after initial treatment, the locoregional recurrence rate of patients in the granzyme B positive group was much higher compared with patients in the granzyme B negative group. In addition, compared with patients in the granzyme B negative group, patients in the granzyme B positive group also had an increased risk of systemic disease recurrence and a decreased overall survival rate. CONCLUSIONS: The data indicate that the cytotoxic granule-associated protein, granzyme B, may be used as an additional marker for identifying NK/T-cell lymphoma and as a prognostic indicator for risk assessment in patients with angiocentric lymphoma of the head and neck.

Adult↗
PubMed2001

Human mdm2 mediates multiple mono-ubiquitination of p53 by a mechanism requiring enzyme isomerization.

The mdm2 gene product is an important regulator of p53 function and stability. mdm2 is an E3 ubiquitin ligase for p53 and the RING finger domain of mdm2 is critical for ligase activity. Ubiquitin (Ub) conjugation is a general targeting modification and poly-ubiquitin chains specifically target proteins to the proteasome for degradation. In this report, we show that the multistep cascade of mdm2-mediated p53 ubiquitination can be reduced to three purified recombinant proteins: ubiquitin-conjugated E2, mdm2, and p53. This simplification allows enzymatic analysis of the isolated ligase reaction. The simplified reaction recapitulates the ubiquitination of p53 observed with individual components and the p53-Ub((n)) is qualitatively similar to p53-Ub((n)) detected in lactacystin-treated cells. Surprisingly, we find that p53 is modified with multiple mono-ubiquitin moieties as opposed to a poly-ubiquitin chain. Finally, kinetic analysis indicates the transfer reaction proceeds either through a modified Ping Pong mechanism involving requisite enzyme isomerization steps, or through a Rapid Equilibrium Random Bi Bi mechanism involving very large anti-cooperative interactions between the two substrate binding pockets on the enzyme, mediated through allosteric changes in enzyme structure.

Ethylmaleimide↗
PubMed2001

Isolation and characterization of cultured human periodental ligament fibroblast-specific cDNAs.

The molecular mechanisms that control the function of periodontal ligament (PDL) fibroblasts remain unclear. We speculated that the character of differentiating PDL fibroblasts is defined by the altered expansion of specific genes not found in neighboring gingival fibroblasts in the periodontium. To expand this set, subtractive hybridization was applied between cultured human PDL and gingival fibroblasts to identify genes differentially expressed in PDL. Consequently five candidate clones, PDLs (periodontal ligament specific) 5, -17, -22, -25, and -31 were identified and characterized by homology search, Northern analysis, and in situ hybridization. Although the mRNAs of these clones were expressed by bone marrow cells and rarely by gingival fibroblasts, the highest expression was detected in the PDL cells, which were uniformly distributed throughout the whole PDL. Amongst the five candidate clones, we focused on PDLs17, because it is a hypothetical protein whose biological function has not been reported yet in the database. Polyclonal antiserum raised against PDLs17 peptide was made, and stained the PDL fibroblasts, osteoblast-like cells and stromal cells in the bone marrow, but not gingival fibroblasts. The results suggest that clones, PDLs5, -17, -22, -25, and -31 may be used as PDL fibroblast-specific markers, and that PDLs17 could act as an important factor in the differentiation process of PDL fibroblasts.

Blotting, Northern↗
PubMed2001

Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance.

Previous reports indicate that the expression and/or activity of the protein-tyrosine phosphatase (PTP) LAR are increased in insulin-responsive tissues of obese, insulin-resistant humans and rodents, but it is not known whether these alterations contribute to the pathogenesis of insulin resistance. To address this question, we generated transgenic mice that overexpress human LAR, specifically in muscle, to levels comparable to those reported in insulin-resistant humans. In LAR-transgenic mice, fasting plasma insulin was increased 2.5-fold compared with wild-type controls, whereas fasting glucose was normal. Whole-body glucose disposal and glucose uptake into muscle in vivo were reduced by 39-50%. Insulin injection resulted in normal tyrosyl phosphorylation of the insulin receptor and insulin receptor substrate 1 (IRS-1) in muscle of transgenic mice. However, phosphorylation of IRS-2 was reduced by 62%, PI3' kinase activity associated with phosphotyrosine, IRS-1, or IRS-2 was reduced by 34-57%, and association of p85alpha with both IRS proteins was reduced by 39-52%. Thus, overexpression of LAR in muscle causes whole-body insulin resistance, most likely due to dephosphorylation of specific regulatory phosphotyrosines on IRS proteins. Our data suggest that increased expression and/or activity of LAR or related PTPs in insulin target tissues of obese humans may contribute to the pathogenesis of insulin resistance.

Animals↗
PubMed2001

Oxidative damages are critical in pathogenesis of reflux esophagitis: implication of antioxidants in its treatment.

BACKGROUND: The facts that the severity of reflux esophagitis cannot be accurately predicted on the basis of acid exposure and acid suppression treatment is not enough for the complete healing, suggested that other damaging factors might be involved in pathogenesis of reflux esophagitis. AIMS: The present study was designed to evaluate the oxidative stress as the major pathogenic factor of reflux esophagitis and the importance of antioxidant in treatment of reflux esophagitis. MATERIALS AND METHODS: Reflux esophagitis was induced by the insertion of small caliber ring (3 mm in diameter) into the duodenum 1 cm distal to the ligament of Treitz in rats. RESULTS: DA-9601, a novel antioxidant substance, attenuated the gross esophagitis significantly compared to that treated with ranitidine, histamine-2 receptor antagonist (H2-RA), in a dose-dependent manner. Severe, hemorrhagic, and longitudinal ulcerations were developed in H2-RA pretreated group, whereas mildly scattered erosions were observed in antioxidant-pretreated group. Significantly increased amounts of malondialdehyde (MDA), increased NF-kappaB activation, and the mucosal depletion of reduced glutathione (GSH) were observed in the esophagus of reflux esophagitis. H2-RA treatment didn't affect the levels of GSH and MDA, whereas DA-9601 attenuated the decrement of the GSH levels and significantly decreased lipid peroxides in the esophagus. Antioxidants treatment showed significant reductions in the activation of NF-kappaB, inflammation-associated transcription factor, especially p50 component in accordance with significant higher levels of NF-kappaB repressor, IkappaBalpha expression. CONCLUSION: Oxygen-derived free radicals seem to be one of the important mediators in generation of reflux esophagitis, which suggests that the combination of antioxidant and anti-secretory medications will be ideal and more beneficial in the prevention and treatment of reflux esophagitis than currently prescribed antisecretory treatment alone.

Animals↗
PubMed2001

Molecular cloning and expression pattern of porcine myeloid DAP12-associating lectin-1.

DAP12 is an ITAM-bearing membrane protein that is associated with activating receptors in natural killer cells, granulocytes, macrophages, and monocytes. Myeloid DAP12-associating lectin-1 (MDL-1) is a type II membrane protein that associates with DAP12. In this study, we report the molecular cloning of two isoforms of porcine MDL-1 cDNA from pulmonary alveolar macrophages. The porcine MDL-1 short form has 165 amino acids and 70% sequence identity with the mouse MDL-1 short form. The long form has 20 more amino acids in the stalk region and 71% sequence identity with human MDL-1 and 67% with the mouse MDL-1 long form. Porcine MDL-1 contains a conserved lysine in the transmembrane domain. There are six putative N-linked glycosylation sites in the MDL-1 long form. MDL-1 transcripts were detected exclusively in macrophages and monocytes by RT-PCR. When transfected into 293 cells, porcine MDL-1 is expressed on the cell surface associated with DAP12.

Amino Acid Sequence↗
PubMed2001

Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with neurobehavioral test scores in South Korean lead workers.

The authors performed a cross-sectional study to evaluate associations between blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead and measures of neurobehavioral and peripheral nervous system function among 803 lead-exposed workers and 135 unexposed controls in South Korea. The workers and controls were enrolled in the study between October 1997 and August 1999. Central nervous system function was assessed with a modified version of the World Health Organization Neurobehavioral Core Test Battery. Peripheral nervous system function was assessed by measuring pinch and grip strength and peripheral vibration thresholds. After adjustment for covariates, the signs of the beta coefficients for blood lead were negative for 16 of the 19 tests and blood lead was a significant predictor of worse performance on eight tests. On average, for the eight tests that were significantly associated with blood lead levels, an increase in blood lead of 5 microg/dl was equivalent to an increase of 1.05 years in age. In contrast, after adjustment for covariates, tibia lead level was not associated with neurobehavioral test scores. Associations with DMSA-chelatable lead were similar to those for blood lead. In these currently exposed workers, blood lead was a better predictor of neurobehavioral performance than was tibia or DMSA-chelatable lead, mainly in the domains of executive abilities, manual dexterity, and peripheral motor strength.

Adult↗
PubMed2001

Haloperidol and clozapine increase neural activity in the rat prefrontal cortex.

Haloperidol and clozapine have been widely used to alleviate schizophrenic symptoms, but their physiological effects in the prefrontal cortex (PFC) are not known. Effects of haloperidol and clozapine on single unit activity were investigated in the medial PFC of anesthetized rats. Injection (intraperitoneal) of haloperidol (1 mg/kg) or clozapine (20 mg/kg) significantly elevated discharge rates of PFC neurons. Considering that hypofrontality is one characteristic of schizophrenic symptoms, these results raise the possibility that enhancement of PFC neural activity contributes to therapeutic effects of haloperidol and clozapine.

Action Potentials↗
PubMed2001

Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver.

The earliest defect in developing type 2 diabetes is insulin resistance, characterized by decreased glucose transport and metabolism in muscle and adipocytes. The glucose transporter GLUT4 mediates insulin-stimulated glucose uptake in adipocytes and muscle by rapidly moving from intracellular storage sites to the plasma membrane. In insulin-resistant states such as obesity and type 2 diabetes, GLUT4 expression is decreased in adipose tissue but preserved in muscle. Because skeletal muscle is the main site of insulin-stimulated glucose uptake, the role of adipose tissue GLUT4 downregulation in the pathogenesis of insulin resistance and diabetes is unclear. To determine the role of adipose GLUT4 in glucose homeostasis, we used Cre/loxP DNA recombination to generate mice with adipose-selective reduction of GLUT4 (G4A-/-). Here we show that these mice have normal growth and adipose mass despite markedly impaired insulin-stimulated glucose uptake in adipocytes. Although GLUT4 expression is preserved in muscle, these mice develop insulin resistance in muscle and liver, manifested by decreased biological responses and impaired activation of phosphoinositide-3-OH kinase. G4A-/- mice develop glucose intolerance and hyperinsulinaemia. Thus, downregulation of GLUT4 and glucose transport selectively in adipose tissue can cause insulin resistance and thereby increase the risk of developing diabetes.

Adipocytes↗
PubMed2001

Uncoupling protein 3 (UCP3) stimulates glucose uptake in muscle cells through a phosphoinositide 3-kinase-dependent mechanism.

UCP3 is a mitochondrial membrane protein expressed in humans selectively in skeletal muscle. To determine the mechanisms by which UCP3 plays a role in regulating glucose metabolism, we expressed human UCP3 in L6 myotubes by adenovirus-mediated gene transfer and in H(9)C(2) cardiomyoblasts by stable transfection with a tetracycline-repressible UCP3 construct. Expression of UCP3 in L6 myotubes increased 2-deoxyglucose uptake 2-fold and cell surface GLUT4 2.3-fold, thereby reaching maximally insulin-stimulated levels in control myotubes. Wortmannin, LY 294002, or the tyrosine kinase inhibitor genistein abolished the effect of UCP3 on glucose uptake, and wortmannin inhibited UCP3-induced GLUT4 cell surface recruitment. UCP3 overexpression increased phosphotyrosine-associated phosphoinositide 3-kinase (PI3K) activity 2.2-fold compared with control cells (p < 0.05). UCP3 overexpression increased lactate release 1.5- to 2-fold above control cells, indicating increased glucose metabolism. In H(9)C(2) cardiomyoblasts stably transfected with UCP3 under control of a tetracycline-repressible promotor, removal of doxycycline resulted in detectable levels of UCP3 at 12 h and 2.2-fold induction at 7 days compared with 12 h. In parallel, glucose transport increased 1.3- and 2-fold at 12 h and 7 days, respectively, and the stimulation was inhibited by wortmannin or genistein. p85 association with membranes was increased 5.5-fold and phosphotyrosine-associated PI3K activity 3.8-fold. In contrast, overexpression of UCP3 in 3T3-L1 adipocytes did not alter glucose uptake, suggesting tissue-specific effects of human UCP3. Thus, UCP3 stimulates glucose transport and GLUT4 translocation to the cell surface in cardiac and skeletal muscle cells by activating a PI3K dependent pathway.

3T3 Cells↗
PubMed2001

Polyesters from microorganisms.

Bacterial polyesters have been found to have useful properties for applications as thermoplastics, elastomers, and adhesives and are biodegradable and biocompatible. Poly(3-hydroxyalkanoates) (PHAs) and poly(beta-malate) are the most representative polyesters synthesized by microorganisms. PHAs containing a wide variety of repeating units can be produced by bacteria, including those containing many types of pendant functional groups which can be synthesized by microorganisms that are grown on unnatural organic substrates. Poly(beta-malate) is of interest primarily for medical applications, especially for drug delivery systems. In this chapter, the bacterial production and properties of poly(3-hydroxyalkanoates) and poly(beta-malate) are described with emphasis on the former.

Acyltransferases↗
PubMed2001

Molecular cloning and characterization of pig immunoreceptor DAP10 and NKG2D.

Pig immunoreceptor DAP10 cDNA was cloned from a peripheral blood lymphocyte (PBL) cDNA library using human DAP10 cDNA as a probe. The length of the pig DAP10 cDNA is 465 bp and it contains an open reading frame of 237 bp. The predicted polypeptide sequence is 79 amino acids, consisting of an 18-amino acid leader, a 16-amino acid extracellular domain, a 24-amino acid transmembrane segment, and a 21-amino acid cytoplasmic domain. The amino acid sequence of pig DAP10 has 68% and 78% sequence identity with human DAP10 and mouse DAP10, respectively. Pig DAP10 has a conserved aspartic acid in the transmembrane domain, two cysteines in the extracellular domain, and a phophatidylinositol-3 kinase-binding site (YxxM) in the cytoplasmic region. Genomic organization reveals that pig DAP10 comprises four exons and three introns. Pig DAP10 and DAP12 are genetically linked on Chromosome (Chr) 6 at 6q21 in opposite transcriptional orientation, separated by 152 bp. In Northern blot analysis, DAP10 transcripts were detected predominantly in lymphohematopoietic tissues. Pig NKG2D cDNA has an open reading frame of 642 bp. Its expected polypeptide sequence is 214 amino acids. Pig NKG2D has 66% sequence identity with human NKG2D and 56% identity with mouse NKG2D. The NKG2D gene maps to pig Chr 5q25. RT-PCR analysis reveals that pig NKG2D transcripts are expressed in PBLs, NK cells, macrophages, and monocytes. When transiently transfected into COS-7 cells, pig NKG2D requires DAP10 for cell surface expression.

Amino Acid Sequence↗
PubMed2001

Solution structure of the SL1 RNA of the M1 double-stranded RNA virus of Saccharomyces cerevisiae.

The 20-nucleotide SL1 VBS RNA, 5'-GGAGACGC[GAUUC]GCGCUCC (bulged A underlined and loop bases in brackets), plays a crucial role in viral particle binding to the plus strand and packaging of the RNA. Its structure was determined by NMR spectroscopy. Structure calculations gave a precisely defined structure, with an average pairwise root mean square deviation (RMSD) of 1.28 A for the entire molecule, 0.57 A for the loop region (C8-G14), and 0.46 A for the bulge region (G4-G7, C15-C17). Base stacking continues for three nucleotides on the 5' side of the loop. The final structure contains a single hydrogen bond involving the guanine imino proton and the carbonyl O(2) of the cytosine between the nucleotides on the 5' and 3' ends of the loop, although they do not form a Watson-Crick base pair. All three pyrimidine bases in the loop point toward the major groove, which implies that Cap-Pol protein may recognize the major groove of the SL1 loop region. The bulged A5 residue is stacked in the stem, but nuclear Overhauser enhancements (NOEs) suggest that A5 spends part of the time in the bulged-out conformation. The rigid conformation of the upper stem and loop regions may allow the SL1 VBS RNA to interact with Cap-Pol protein without drastically changing its own conformation.

Base Sequence↗