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Biomedical subjects

Y G Kim

Publications and source records attributed to Y G Kim.

At least 91 records · Page 5Linked to original sources

Discordant evolution of asymptomatic proteinuria in identical twins.

We describe a pair of 17-year-old identical twin brothers with asymptomatic proteinuria, one of whom showed focal segmental glomerulosclerosis (FSGS) while the other showed immunoglobulin M (IgM) nephropathy. For each twin, audiological examination was normal. There was no family history of renal failure, deafness, or hematuria. HLA typing revealed an identical phenotype consisting of A25, A33, B44, B54, Cw1, Cw7, DR7 and DRB1. There is still controversy about whether minimal change disease, IgM nephropathy, and FSGS are discrete entities or different aspects of the same disease. The coexistence of IgM nephropathy and FSGS in identical twins suggests that the same genetic factors may be involved in the development of both diseases. However, although the brothers are identical twins, they had different eating habits and body weight. The twin who preferred to eat a protein-rich diet and who was heavier developed early proteinuria and manifested FSGS on renal biopsy. The discordant evolution of asymptomatic proteinuria in identical twins may provide a clue for the existence of environmental factors on the progression from IgM nephropathy to FSGS. Therefore, this report provides indirect support for the hypothesis that IgM nephropathy and FSGS represent different aspects in the spectrum of a single disease.

Adolescent↗

Suppression of NF-kappaB activation in normal T cells by supernatant fluid from human renal cell carcinomas.

T lymphocytes from patients with renal cell carcinoma (RCC) show reduced immune function and impaired activation of the transcription factor, NF-kappaB. We determined the mechanism of NF-kappaB suppression in T cells of RCC patient and determined whether supernatant fluid from RCC explants (RCC-S) induced the same phenotype of NF-kappaB suppression in normal T cells that is observed in patient T cells. The pattern of kappaB-binding activity in T cells of RCC patient was altered as compared to that seen in T cells obtained from normal volunteers. In some patients, no activation of RelA/NFkappaB1-binding activity was detectable, while in others kappaB-binding activity was modestly induced but the duration was reduced. IkappaBalpha was degraded normally following stimulation in both normal controls and T cells from RCC patients. RCC-S did not alter the cytoplasmic levels of RelA and NF-kappaB1 but did suppress their nuclear localization and inhibited the activation of RelA/NF-kappaB1 binding complexes. These results show that RCC-S can induce in normal T cells the same phenotype of impaired NF-kappaB activation that is detected in T cells of RCC patient. It also appears that NF-kappaB suppression by RCC-S may contribute to the immunosuppression of host immunity.

Carcinoma, Renal Cell↗

Setting shrinkage and hygroscopic expansion of resin-modified glass-ionomer in experimental cylindrical cavities.

The effects of the C-value (bonded surface area/unbonded surface area) and the volume of the cavity on the volumetric dimensional changes [volumetric setting shrinkage (VSS) and volumetric hygroscopic expansion (VHE)] of a resin-modified glass-ionomer (RMGI) filled in experimental cylindrical cavities were evaluated. The VSS and the VHE rate decreased with increasing C-value. There was a high inverse regression between the cavity C-value and volumetric dimensional changes, but a low regression between cavity volume and volumetric dimensional changes. Therefore, it was thought that greater contraction stress would remain in high C-value cavities than low C-value cavities during the setting process. It was also confirmed that the volumetric dimensional changes of RMGI in cavity were influenced primarily by the cavity C-value.

Absorption↗

Determination of a new asiatic acid derivative, AS 2-006A in rat plasma and urine, and human plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for the determination of a new wound healing agent, AS 2-006A (ethoxymethyl 2-oxo-3, 23-O-isopropylideneasiatate), in rat plasma and urine, and human plasma. The sample preparation was simple: 2 volumes of acetonitrile were added to the biological samples to deproteinize it. A 50-microl aliquot of the supernatant was injected onto the reversed-phase column. The mobile phase employed was acetonitrile : H2O (9:1, v/v) and run at a flow rate of 1.1 ml/min. The column effluent was monitored by a UV detector set at 205 nm. The retention time for AS 2-006A was approximately 29.5 min. The detection limits for AS 2-006A in rat and human plasma were both 1 microg/ml, and in rat urine was 2 microg/ml. The coefficients of variation of the assay (within-day and between-day) were generally low (below 10.8%) for rat plasma and urine, and human plasma. No interferences from endogenous substances were found.

Animals↗

Spectroscopic characterization of a DNA-binding domain, Z alpha, from the editing enzyme, dsRNA adenosine deaminase: evidence for left-handed Z-DNA in the Z alpha-DNA complex.

Double-stranded RNA adenosine deaminase (ADAR1) is an ubiquitous enzyme in metazoa that edits pre-mRNA changing adenosine to inosine in regions of double-stranded RNA. Zalpha, an N-terminal domain of human ADAR1 encompassing 76 amino acid residues, shows apparent specificity for the left-handed Z-DNA conformation adopted by alternating (dGdC) polymers modified by bromination or methylation, as well as for (dGdC)13 inserts present in supercoiled plasmids. Here, a combination of circular dichroism, fluorescence, and gel-retardation studies is utilized to characterize recombinant Zalpha peptide and to examine its interaction with DNA. Results from laser-Raman spectroscopy experiments provide direct evidence for the existence of Z-DNA in peptide-DNA complexes.

Adenosine Deaminase↗

Structure-related inhibition of human hepatic caffeine N3-demethylation by naturally occurring flavonoids.

The effects of flavonoids on caffeine N3-demethylation, a marker activity of CYP1A2, in human liver microsomes were investigated to elucidate the inhibition mechanism and the structure-activity relationship. Caffeine N3-demethylase activity was inhibited by the presence of various flavonoids, whose structures seem to be closely related to the degree of inhibition. Among twenty-one compounds tested, the most active was chrysin with an IC50 value of 0.2 microM. Others had IC50 values ranging from 1 to more than 500 microM. Kinetic analysis revealed that the mechanism of inhibition varied among the flavonoids. The inhibitory effect was postulated to be governed by factors such as the number of hydroxyl groups and glycosylation of these free hydroxyl groups. An increase in the number of free hydroxyl groups reduced the inhibitory effect on P450 activity. Analysis of the quantitative structure-activity relationship (QSAR) showed that the volume to surface area ratio was the most effective factor on the inhibition of caffeine N3-demethylation, and the electron densities on the C3 and C4' atoms exercised significant influence on the inhibitory effect. The calculated inhibitory effect of flavonoids on CYP1A2 activity was highly correlated with the antimutagenicity of flavonoids in 2-amino-3,4-dimethylimidazo[4,5-flquinoline (MelQ)-induced umu response.

Anticarcinogenic Agents↗

A multifunctional repeated motif is present in human bifunctional tRNA synthetase.

Tandem repeats located in the human bifunctional glutamyl-prolyl-tRNA synthetase (EPRS) have been found in many different eukaryotic tRNA synthetases and were previously shown to interact with another distinct repeated motifs in human isoleucyl-tRNA synthetase. Nuclear magnetic resonance and differential scanning calorimetry analyses of an isolated EPRS repeat showed that it consists of a helix-turn-helix with a melting temperature of 59 degrees C. Specific interaction of the EPRS repeats with those of isoleucyl-tRNA synthetase was confirmed by in vitro binding assays and shown to have a dissociation constant of approximately 2.9 microM. The EPRS repeats also showed the binding activity to the N-terminal motif of arginyl-tRNA synthetase as well as to various nucleic acids, including tRNA. Results of the present work suggest that the region comprising the repeated motifs of EPRS provides potential sites for interactions with various biological molecules and thus plays diverse roles in the cell.

Amino Acid Sequence↗

Pharmacokinetics of a new reversible proton pump inhibitor, YH1885, after intravenous and oral administrations to rats and dogs: hepatic first-pass effect in rats.

The pharmacokinetics of YH1885 were evaluated after intravenous (iv) and oral administrations of the drug to rats and dogs. The reason for the low extent of bioavailability (F) of YH1885 after oral administration of the drug to rats and the absorption of the drug from various rat gastrointestinal (GI) segments were also investigated. After iv administration of YH1885, 5-20 mg kg(-1), to rats, the pharmacokinetic parameters of YH1885 seem to be independent of the drug at the dose ranges studied. After oral administration of YH1885, 50-200 mg kg(-1), to rats, the area under the plasma concentration-time curve from time zero to 12 or 24 h (AUC(0-12 h) or AUC(0-24 h)) was proportional to the oral dose of the drug, 50-100 mg kg(-1), however, the AUC(0-24 h) value at 200 mg kg(-1) increased with less proportion to the dose increase (324, 689, and 815 microg x min mL(-1) for 50, 100, and 200 mg kg(-1), respectively) due to the poor water solubility of the drug. This was proved by the considerable increase in the percentages of the oral dose remaining in the entire GI tract as unchanged YH1885 at 24 h (11.8, 15.3, and 42.8% for 50, 100, and 200 mg kg(-1), respectively). The F value after oral administration of YH1885 to rats was relatively low; the value was approximately 40% at the oral dose of 50 and 100 mg kg(-1). The reason for the low F in rats was investigated. The liver showed the highest metabolic activity for YH1885 based on an in vitro rat tissue homogenate study; hence, the liver first-pass effect was estimated. The value of AUC after intraportal administration of the drug, 5 mg kg(-1), was approximately 70% (116 versus 163 microg x min mL(-1)) of that after iv administration of the drug, 5 mg kg(-1), to rats; the liver first-pass effect of YH1885 in rats was estimated to be approximately 30%. The total body clearance of YH1885 after iv administration of the drug, 5-20 mg kg(-1), to rats were considerably lower than the cardiac output of rats, indicating that the lung and/or heart first-pass effect of YH1885 could be negligible in rats. After oral administration of YH1885, 50 and 100 mg kg(-1), to rats, the F value was approximately 40%, and approximately 15% of the oral dose was recovered from the entire GI tract as unchanged YH1885 at 24 h, and 30% of the oral dose disappeared with the liver first-pass effect. Therefore, the remainder, approximately 15% of the oral dose, could have disappeared with the small intestine first-pass effect and/or degradation of the drug in the GI tract. YH1885 was absorbed from ileum, duodenum, and jejunum of rat, however, YH1885 was under the detection limit in plasma when the drug was instilled into the rat stomach and large intestine. After iv administration of YH1885, 5-20 mg kg(-1), to dogs, the pharmacokinetic parameters of YH1885 also seemed to be independent of the drug at the dose ranges studied. However, after oral administration of YH1885, 0.5 and 2 g per whole body weight, to dogs, the AUC(0-10 h) values were not significantly different (96.8 versus 98.2 microg x min mL(-1)) and this could be due to the poor water-solubility of the drug. YH1885 was not detected in the urine after both iv and oral administration of the drug to both rats and dogs.

Administration, Oral↗

Heterogeneity of human papillomavirus DNA in a patient with Bowenoid papulosis that progressed to squamous cell carcinoma.

Bowenoid papulosis (BP) of the genitalia, characterized by the histological findings of a squamous cell carcinoma, follows a largely benign clinical course. The detection of oncogenic human papilloma viruses (HPV) from BP points to an aetiological role of these viral infections. A 47-year-old man with multiple genital skin lesions was seen over a 10-year period with the diagnosis of BP. Recently, he attended again with a recurrent genital tumour that was diagnosed as squamous cell carcinoma. His genital lesions progressed and became polymorphic in appearance, from a wart-like tumour to a reddish invasive plaque. To screen for the presence of different HPV sequences from different skin lesions and to correlate each HPV type with distinct clinical manifestations, polymerase chain reaction and single-strand conformational polymorphism (PCR-SSCP) were performed. PCR-SSCP revealed the presence of several types of HPV from different genital lesions. Sequencing results disclosed that he had a mixed infection of HPV6b, HPV16, HPV18 and HPV33, respectively. Interestingly, the clinical findings were fairly well correlated with the oncogenic potential of HPV found from each lesion.

Bowen's Disease↗

Prevalence and risk factors of urinary stones in Koreans.

To estimate the prevalence of urinary stone disease in Koreans, and to determine the inter-relationships between urinary stone disease and various epidemiological factors, 1,521 controls and 1,177 cases with urinary stones were evaluated. Of special interest in this study were: 1) proportion of past urinary stone history among controls; 1.9% 2) the point prevalence rate of urinary stones among controls; 0.2% 3) the recurrence rate of urinary stones (the proportion of past history of urinary stone) among cases; 56.8% 4) high incidences (76.3%) in the thirties to the fifties among cases 5) the risk factors for urolithogenesis; obesity [higher than 25 of BMI (body mass index, weight/height2)], more than 10 year-experience as a production worker, past stone history, familial stone history, low physical activity (< 2,000 Kcal/day), and low intake of fruit. However, the well-known risk factors for urinary stones; over intake of meat or fish and milk or dairy products, perspiration, amount and kind of drinking water, and stress unexpectedly were not significantly different between the controls and the cases.

Adolescent↗

Site-specific cleavage of DNA-RNA hybrids by zinc finger/FokI cleavage domain fusions.

Zinc-finger proteins of the Cys2His2 type bind DNA-RNA hybrids with affinities comparable to those for DNA duplexes. Such zinc-finger proteins were converted into site-specific cleaving enzymes by fusing them to the FokI cleavage domain. The fusion proteins are active and under optimal conditions cleave DNA duplexes in a sequence-specific manner. These fusions also exhibit site-specific cleavage of the DNA strand within DNA-RNA hybrids albeit at a lower efficiency (approximately 50-fold) compared to the cleavage of the DNA duplexes. These engineered endonucleases represent the first of their kind in terms of their DNA-RNA cleavage properties, and they may have important biological applications.

Base Sequence↗

Construction of a Z-DNA-specific restriction endonuclease.

Novel restriction enzymes can be created by fusing the nuclease domain of FokI endonuclease with defined DNA binding domains. Recently, we have characterized a domain (Z alpha) from the N-terminal region of human double-stranded RNA adenosine deaminase (hADAR1), which binds the Z-conformation with high specificity. Here we report creation of a conformation-specific endonuclease, Z alpha nuclease, which is a chimera of Z alpha and FokI nuclease. Purified Z alpha nuclease cleaves negatively supercoiled plasmids only when they contain a Z-DNA forming insert, such as (dC-dG)13. The precise location of the cleavage sites was determined by primer extension. Cutting has been mapped to the edge of the B-Z junction, suggesting that Z alpha nuclease binds within the Z-DNA insert, but cleaves in the nearby B-DNA, by using a mechanism similar to type IIs restriction enzymes. These data show that Z alpha binds Z-DNA in an environment similar to that in a cell. Z alpha nuclease, a structure-specific restriction enzyme, may be a useful tool for further study of the biological role of Z-DNA.

Cloning, Molecular↗

A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase.

Editing of RNA changes the read-out of information from DNA by altering the nucleotide sequence of a transcript. One type of RNA editing found in all metazoans uses double-stranded RNA (dsRNA) as a substrate and results in the deamination of adenosine to give inosine, which is translated as guanosine. Editing thus allows variant proteins to be produced from a single pre-mRNA. A mechanism by which dsRNA substrates form is through pairing of intronic and exonic sequences before the removal of noncoding sequences by splicing. Here we report that the RNA editing enzyme, human dsRNA adenosine deaminase (DRADA1, or ADAR1) contains a domain (Zalpha) that binds specifically to the left-handed Z-DNA conformation with high affinity (KD = 4 nM). As formation of Z-DNA in vivo occurs 5' to, or behind, a moving RNA polymerase during transcription, recognition of Z-DNA by DRADA1 provides a plausible mechanism by which DRADA1 can be targeted to a nascent RNA so that editing occurs before splicing. Analysis of sequences related to Zalpha has allowed identification of motifs common to this class of nucleic acid binding domain.

Adenosine Deaminase↗

Effect of mandibular setback surgery on occlusal force.

PURPOSE: This study investigated the effect of mandibular setback surgery on occlusal force and evaluated the extent to which postsurgical changes in such force can be explained by the type of operation, the duration of maxillo-mandibular fixation (MMF), and the changes in the mechanical advantage of the jaw musculature. MATERIALS AND METHODS: Maximal molar bite force was measured before surgery and at MMF removal, and 3, 6, and 12 months thereafter in 26 patients with mandibular prognothism. To correlate bite force and skeletal change, the cephalometric tracings were measured, tabulated, and statistically analyzed. RESULTS: Mean bite force was 13.7 kg before surgery, 7.6 kg at MMF removal, 14.2 kg at 3 months, 19.7 kg at 6 months, and 26.1 kg at 12 months post-surgery. The bite force was positively correlated with the surgical change in mandibular plane angle and mandibular body length. The recovery of bite force was significantly affected by the type of operation and duration of MMF. CONCLUSIONS: To hasten recovery and increase bite force after orthognathic surgery, long periods of MMF and injury to the masticatory muscles should be avoided.

Adolescent↗

Inflammatory nodules of the lower legs: a clinical and histological analysis of 134 cases in Korea.

We analysed 134 Korean cases with inflammatory nodules of the lower legs on the basis of clinicopathological findings, responsiveness to various therapeutic agents, and clinical course. There were 53 cases of erythema induratum (EI), 18 of erythema nodosum (EN), 40 of EN-like lesions of Behcet's disease, 15 of other entities, including superficial migratory thrombophlebitis, cutaneous periarteritis nodosa, sarcoidosis, malignant lymphoma, Churg-Strauss syndrome, and parasitosis, and eight unclassified cases. The unclassified group was composed of a spectrum of diseases with clinicopathologic features ranging between those typical of EN and EI. The present study revealed that the profiles of diseases featuring inflammatory nodules of the lower legs in Korea differed from those found in other areas. These geographic and demographic differences should be kept in mind when managing a patient with inflammatory nodules of the lower legs.

Adolescent↗

In vitro and in vivo antibacterial efficacies of CFC-222, a new fluoroquinolone.

CFC-222 is a novel fluoroquinolone containing a C-7 bicyclic amine moiety with potent antibacterial activities against gram-positive, gram-negative, and anaerobic organisms. We compared the in vitro and in vivo activities of CFC-222 with those of ciprofloxacin, ofloxacin, and lomefloxacin. CFC-222 was more active than the other fluoroquinolones tested against gram-positive bacteria. CFC-222 was particularly active against Streptococcus pneumoniae (MIC at which 90% of isolates are inhibited [MIC90], 0.2 microg/ml), Staphylococcus aureus (MIC90, 0.2 microg/ml for ciprofloxacin-susceptible strains), and Enterococcus faecalis (MIC90, 0.39 microg/ml). Against Escherichia coli and other members of the family Enterobacteriaceae, CFC-222 was slightly less active than ciprofloxacin (MIC90s for E. coli, 0.1 and 0.025 microg/ml, respectively). The in vitro activity of CFC-222 was not influenced by inoculum size, medium composition, or the presence of horse serum. However, its activity was decreased significantly by a change in the pH of the medium from 7.0 to 6.0, as was the case for the other quinolones tested. The in vivo protective efficacy of CFC-222 by oral administration was greater than those of the other quinolones tested in a mouse model of intraperitoneally inoculated systemic infection caused by S. aureus. CFC-222 exhibited efficacy comparable to that of ciprofloxacin in the same model of infection caused by gram-negative organisms, such as E. coli and Klebsiella pneumoniae. In this infection model, CFC-222 was slightly less active than ciprofloxacin against Pseudomonas aeruginosa. These results suggest that CFC-222 may be a promising therapeutic agent in various bacterial infections.

Animals↗