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Biomedical subjects

D S Kim

Publications and source records attributed to D S Kim.

At least 19 recordsLinked to original sources
PubMed1998

Expression of calcium channel alpha1A mRNA and protein in the leaner mouse (tgla/tgla) cerebellum.

Homozygous leaner mice carry an autosomal recessive mutation in the Ca2+ channel subunit gene, alpha1A, causing them to exhibit severe ataxia, petit-mal-like epilepsy and a myoclonus-like movement disorder. Expression of alpha1A mRNA in cerebella from 20-day-old homozygous leaner mice was compared to control mice, using in situ hybridization histochemistry. Expression of alpha1A protein was examined in cerebella from 20-day-old homozygous leaner and control mice using immunocytochemistry. No differences in either mRNA or protein expression of the alpha1A subunit were observed when homozygous leaner mice were compared to age-matched controls. Therefore, functional alterations in P/Q-Type Ca2+ channels containing the alpha1A subunit need to be explored to further understand the relationship of mutations in the alpha1A gene to the pathogenesis of the neurologic disorders occurring in leaner mice.

Animals↗
PubMed1998

X-ray diffraction studies on the structural changes of rigor muscles induced by binding of phosphate analogs in the presence of MgADP.

To clarify the structure of the ATP hydrolysis intermediates (ADP.Pi bound state) formed by actomyosin crossbridges, the effects of various phosphate analogs in the presence of MgADP on the structures of the thin and thick filaments in glycerinated rabbit psoas muscle fibers in the rigor state have been investigated by X-ray diffraction with a short exposure time using synchrotron radiation. When MgADP and phosphate analogs such as metallofluorides (BeFx = 3,4 and AlF4) and vanadate (VO4(Vi)) were added to rigor fibers in the presence of the ATP-depletion backup system, the intensities of the actin-based layer lines were markedly weakened. The greatest effect (approximately 50% decrease in intensity) was observed in the presence of BeFx among the analogs examined. The intensity distribution of the 5.9 nm actin-based layer line shifted towards that observed in the Ca(2+)-activated fibers, while the first actin layer line at approximately 1/36.7 nm-1 retained a rigor-like profile with an intensity weakened by approximately 50%. The intensity of the equatorial 10 reflection increased while that of the 11 reflection changed little, resulting in only a small increase (approximately 1.7 fold) in the intensity ratio of the 10 to the 11 reflection. No resting-like pattern appeared upon the addition of MgADP and BeFx. These results indicate that a substantial fraction (approximately 40%) of the myosin heads dissociate from actin but the detached heads remain in the vicinity of the actin filaments when MgADP and BeFx bind. The states produced by binding phosphate analogs to a rigor muscle differ from the resting-like state produced by adding them to a contracting muscle (Takemori et al., J. Biochem. (Tokyo) 117 (1995) 603-608). Our conclusion put forward to explain the data is that one of the two heads of a crossbridge is detached and the other retains a rigor-like attachment.

Adenosine Diphosphate↗
PubMed1998

Purification and molecular cloning of a platelet aggregation inhibitor from the snake (Agkistrodon halys brevicaudus) venom.

A platelet glycoprotein IIb-IIIa (GP IIb-IIIa) antagonist, salmosin, was purified to homogeneity from Korean snake (Agkistrodon halys brevicaudus) venom by means of chromatographic fractionations. We have isolated the cDNA encoding salmosin by using the cDNA library of the snake venom gland and analyzed its complete nucleotide sequence. The molecular identity was confirmed by comparison of the deduced amino acid sequence with the directly determined primary structure of salmosin. This protein is a single-chain polypeptide composed of 73 amino acids including 12 cysteines as well as the sequence Arg-Gly-Asp, a proposed recognition site of adhesive proteins. The primary sequence of salmosin shows considerable homology to previously described proteins of snake venom GP IIb-IIIa antagonist family. A molecular mass of 7474 for the protein was determined by matrix-assisted laser desorption ionization mass spectrometry. Salmosin inhibits GP IIb-IIIa binding to immobilized fibrinogen with an IC50 of 2.2 nM and ADP-induced platelet aggregation with an IC50 of 131 nM, respectively. This work demonstrates the purification, characterization, and cDNA cloning of salmosin, a platelet aggregation inhibitor that may have therapeutic potential as an antithrombotic agent.

Agkistrodon↗
PubMed1998

Magnone A and B, novel anti-PAF tetrahydrofuran lignans from the flower buds of Magnolia fargesii.

In a search for platelet-activating-factor (PAF) antagonists, two new lignan compounds were isolated from the Chinese crude drug shin-i, the flower buds of Magnolia fargesii. Their structures were elucidated as (2S,3R,4R)-tetrahydro-2-(3,4-dimethoxyphenyl)-4-(3, 4-dimethoxybenzoyl)-3-(hydroxymethyl)furan (magnone A, 1) and (2S,3R, 4R)-tetrahydro-2-(3,4,5-trimethoxyphenyl)-4-(3, 4-dimethoxybenzoyl)-3-(hydroxymethyl)furan (magnone B, 2). Magnones A and B showed antagonistic activity against PAF in the [3H]PAF receptor binding assay with the IC50 values of 3.8 x 10(-5) M and 2.7 x 10(-5) M, respectively.

Animals↗
PubMed1998

Tyrosine kinase inhibitors, emodin and its derivative repress HER-2/neu-induced cellular transformation and metastasis-associated properties.

We have previously shown that emodin suppresses tyrosine kinase activity of HER-2/neu-encoded p185neu receptor tyrosine kinase. In this study, we examine the relationship between the chemical structure and the activity of emodin and nine derivatives, and identified that one methyl, one hydroxy, and one carbonyl functional groups are critical for the biological activities of emodin. We also found that one of the derivatives 10-(4-acetamidobenzylidene)-9-anthrone (DK-V-47) is more effective than emodin in repressing the tyrosine phosphorylation of p185neu and in inhibiting the proliferation and transformation of HER-2/neu-overexpressing human breast cancer cells. Using mutation-activated HER-2/neu transformed 3T3 cells, we also investigated whether emodin and DK-V-47 can inhibit malignant transformation induced solely by the HER-2/neu oncogene. We found that DK-V-47 is more potent than emodin in suppressing transformation phenotypes of activated HER-2/neu transformed 3T3 cells including anchorage-dependent and -independent growth, metastasis-associated properties. These results clearly indicate that the inhibition of p185neu tyrosine kinase by both emodin and DK-V-47 is capable of suppressing the HER-2/neu associated transformed phenotypes including the ability to induce metastatic potential. Our results also support the chemotherapeutic implications of the use of either emodin or DK-V-47 to target HER-2/neu-overexpressing cancer cells.

3T3 Cells↗
PubMed1998

Can antioxidant supplementation slow the aging process?

The oxidative stress theory of aging is well supported by accumulated evidence from various aging intervention studies. Early antioxidant supplementation studies indicate life span extensions by antioxidant feeding in various experimental organisms. Data collected under tightly controlled conditions show that the feeding of 2-mercaptoethanol (0.25%) effectively prolonged both the median and maximum life spans of mice. Evidence has been obtained showing dietary vitamin E to protect against oxidative damage to DNA in human lymphocytes and white blood cells. Other clear evidence of vitamin E's protective effect has been seen in its suppressive action of LDL oxidation both in vitro and in vivo. New evidence on the physiological roles of antioxidants, in addition to their well-known role as free radical scavengers, is emerging from recent research. For instance, the beneficial effect of vitamin E in improving glucose transport and the insulin sensitivity and its putative role as a regulator of cell proliferation should open new research dimensions. This presentation will review some of the anti-aging aspects of dietary antioxidant supplementation, as well as the potential problems of its long-term administration that stem from our lack of knowledge about free radical metabolism and the regulation of endogenous defense mechanisms.

Aging↗
PubMed1998

Anticomplementary activity of ginseng saponins and their degradation products.

The anticomplementary activity of ginseng saponins and their degradation products obtained by chemical treatment of Korean red ginseng saponins was investigated. The total saponin and its major components showed strong anticomplementary activity and their structure-activity relationship was evaluated.

Complement Inactivator Proteins↗
PubMed1998

Identification of an endonuclease secreted by human B lymphoblastic IM9 cells.

We have identified a Mg(2+)-dependent endonuclease from IM9 cell lysates and culture medium using DNA-native-polyacrylamide gel electrophoresis (DNA-native-PAGE) nuclease assay system. This particular endonuclease activity was not detectable in conventional DNA-SDS-polyacrylamide gel electrophoresis assay system which is similar to the method originally described by Rosenthal and Lacks (A.L. Rosenthal and S.A. Lacks, Anal. Biochem. 80 (1977) 76-90). Experimental results clearly demonstrated that the endonuclease activity was not derived from the fetal calf serum in which the cells were grown, but synthesized in the cell and secreted into the culture medium by IM9 cells. Biosynthesis and subsequent release of the endonuclease into the culture medium were significantly decreased by pretreatment of the cells with actinomycin D. Using supercoiled plasmid DNA as a substrate, the endonuclease activity was determined with the enzyme isolated from the cell culture medium by native-PAGE electroelution. The endonuclease, with Mg2+ alone, was able to catalyze the conversion of the plasmid into linear DNA followed by further degradation. This is the first report demonstrating that a distinct Mg(2+)-dependent endonuclease is secreted by a human immune cell line.

Burkitt Lymphoma↗
PubMed1998

Ginsenoside Rh2 and Rh3 induce differentiation of HL-60 cells into granulocytes: modulation of protein kinase C isoforms during differentiation by ginsenoside Rh2.

Ginsenoside Rh1 or Rh2 differentiated B16 melanoma or F9 teratocarnoma to phenotypic normal melanocyte-like cells or parietal endoderm-like cells. Ginsenoside Rh3 and Rh4 were recently isolated from Panax ginseng, but their biochemical and pharmacological effects remain unidentified. The present study investigated whether the ginsenoside Rh group (G-Rh1, -Rh2, -Rh3 and -Rh4) having similar structures induce differentiation of HL-60 cells and whether protein kinase C (PKC) is involved in differentiation by ginsenoside. Differentiation was assessed by Wright-Giemsa stain and nitroblue tetrazolium reduction. G-Rh2 and G-Rh3 induced differentiation of HL-60 cells into morphologically and functionally granulocytes but G-Rh1 and G-Rh4 did not. G-Rh2 and G-Rh3 arrested the cell cycle at the G1/S phase, consistent with the ability to induce differentiation in a decreasing order of retinoic acid > G-Rh2 > G-Rh3. During differentiation by G-Rh2, Ca2+/phospholipid-dependent PKC activity was increased in both the cytosol and total cell extract and Ca2+/phospholipid-dependent phosphorylation of 38 and 200 kDa endogenous proteins increased, while phosphorylation of 60, 64, 66 and 97 kDa proteins was Ca2+/phospholipid-independent. When cytosolic PKC isoforms were analyzed by immunoblotting, no significant change was observed in the alpha level, however, the immunoreactive 60 kDa band of a similar mass to the PKC catalytic fragment appeared following treatment with G-Rh2. The beta isoform was gradually increased with prolonged treatment. The gamma isoform was not detected in the cytosol of untreated cells, whereas a small amount was detected 5 days after treatment. It is concluded that G-Rh2 and G-Rh3 can induce differentiation of HL-60 cells into granulocytes and modulation of PKC isoform levels may contribute to differentiation of HL-60 cells by G-Rh2.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Anticomplementary activity of constituents from the heartwood of Caesalpinia sappan.

The anticomplementary activity of compounds isolated from the heartwood of Caesalpinia sappan L. (Leguminosae) was investigated. The sterol mixture (campesterol 11.2%, stigmasterol 18.9% and beta-sitosterol 69.9%) was most potent and brazilin, brazilein, and protosappanin E showed a new anticomplementary activity on the complement system in vitro.

Animals↗
PubMed1998

Angioimmunoblastic lymphoma (AILD-type T-cell lymphoma) with hyperplastic germinal centers.

Angioimmunoblastic T-cell lymphoma (or angioimmunoblastic lymphadenopathy with dysgammaglobulinemia [AILD]) was originally considered to be an abnormal immune reaction in which reactive follicles with germinal centers (GCs) are usually absent. When hyperplastic GCs are present along with an angioimmunoblastic reaction, the lesion has been interpreted as a benign hyperimmune reaction. We report seven patients with angioimmunoblastic T-cell lymphoma (AITL) who initially had hyperplastic GCs, shown to be malignant lymphoma by further studies and clinical follow-up. Clonal T-cell populations were observed in all specimens evaluated, and sequential biopsies showed histologic progression to typical AITL in two patients. Clinical presentation was characterized by generalized lymphadenopathy of acute onset, constitutional symptoms, hepatosplenomegaly, skin rash, and polyclonal hypergammaglobulinemia in five patients; regional adenopathy preceded generalized adenopathy in two patients. Five patients had rapid progression of disease, and three patients whose treatment was delayed due to inadequate evidence to diagnose lymphoma died of infection. The initial biopsy findings of each patient were similar and showed angioimmunoblastic proliferation, hyperplastic GCs with ill-defined borders, and interfollicular tingible-body macrophages. These GCs differed from occasional residual follicles of typical AITL in that the GCs were enlarged and hyperplasia of follicular dendritic cells was not seen. Diagnostic clear cells were not observed. Apoptotic bodies were markedly increased and bcl-2+ lymphocytes were sparse compared with typical AITL. Results of in situ hybridization for Epstein-Barr virus were positive in each case. We conclude that hyperplastic germinal centers with ill-defined borders and frequent interfollicular tingible-body macrophages occur in a histologic variant of AITL that is necessary to recognize for early diagnosis and treatment.

Adult↗
PubMed1998

Platelet activating factor antagonist activity of ginsenosides.

Ginseng saponins and their degradation products have been screened for antagonist activity towards [3H]PAF (platelet activating factor) in washed rabbit platelet receptor binding studies. 20(S)- and delta20-ginsenosides Rg3, protopanaxadiol-type saponins, were found to be relatively potent PAF antagonists (IC50 = 4.9 x 10(-5) M and 9.2 x 10(-5) M, respectively).

Animals↗
PubMed1998

Co-cultivation of conjunctival epithelial cells and Chlamydia trachomatis: electron microscopic findings.

This study used primary culture of rabbit conjunctival epithelial cells to investigate the infection process of chlamydia. The epithelial cells isolated from conjunctiva of rabbit were initially cultured for three weeks. After attaining confluence they were infected with Chlamydia trachomatis (C. trachomatis) serotype D, and after co-cultivation for 24, 48, and 96 hours, electron microscopic study was performed. An inclusion body, a characteristic finding of chlamydial infection, was observed in the vicinity of the nucleus after 24 hours of co-cultivation. It contained a large number of elementary and reticulate bodies and their intermediate forms. Infectious particles known as elementary bodies were noted in the inclusion as 20 to 30 microns sized round bodies with an electron dense core. Reticulate bodies were also noted; they too were round but somewhat pleomorphic and larger than elementary bodies. Some reticulate bodies multiplied actively by means of binary fission. In this study, we observed the characteristic changes of C. trachomatis-infected cells; this in-vitro system might provide a suitable model for the study of some aspects of the pathogenesis of ocular chlamydia infection.

Animals↗
PubMed1998

The causative organisms of bacterial meningitis in Korean children, 1986-1995.

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood. Epidemiologic investigations have shown variability in disease risks among different populations and races. In Korea, however, basic epidemiologic information on bacterial meningitis in children is limited. The main purpose of this study was to analyze bacteriologically proven meningitis cases in terms of the relative frequency of causative organisms, mortality rate, and age distribution beyond the neonatal period. Data was obtained from the hospital records who had been diagnosed with bacterial meningitis at 13 general or university hospitals from 1986 through 1995. The patients had at least one positive CSF culture for bacteria. Of 140 cases of CSF culture-proven bacterial meningitis, 46.4% was < or =1 year, 62.1% was < or =2 years, 81.4% was < or =5 years cumulatively. Streptococcus pneumoniae was the most common bacteria responsible for 48 (35.0%) of all cases regardless of age, followed by Haemophilus influenzae for 48 (34.3%) and Neisseria meningitidis for 8 (6.4%) patients. The case fatality rate was 20.0%, 17.1%, and 16.7% for N. meningitidis, S. pneumoniae, and H. influenzae, respectively. In conclusion, the most common organisms of culture-proven bacterial meningitis in the last 10 years have been S. pneumoniae, H. influenzae, and N. meningitidis in order of frequency. Further study should be extended to nation-wide epidemiologic evaluation to show the incidence of bacterial meningitis caused by these three important organisms.

Adolescent↗
PubMed1998

Effects of growth factors on the proliferation of human keratinocytes and fibroblasts in vitro.

Growth/differentiation factor-5 (GDF-5) is a new member of the transforming growth factor-beta (TGF-beta) superfamily of multifunctional peptide growth factors that appear to mediate many key events in cell growth and development. The effects of GDF-5 and other growth factors (epidermal growth factor, EGF; TGF-beta 1) on the proliferation of human keratinocytes and fibroblasts compared with desoximetasone and calcipotriol have been investigated. The proliferation rate was determined by a hemocytometer, MTT assay and the incorporation of [3H]-thymidine. Moreover, cell cycle analyses were performed and the influence on interleukin-1 alpha (IL-1 alpha) production in keratinocytes was measured by enzyme-linked immunosorbent assay (ELISA) because of its pronounced proinflammatory effect. In keratinocytes, GDF-5 stimulated cell proliferation to a minor extent. The drug already proved to be effective at very low concentrations (0.1 ng/ml). Growth stimulatory effects with EGF have been observed only in keratinocyte basal medium (KBM), but not in keratinocyte growth medium (KGM). TGF-beta 1 markedly inhibited the proliferation of keratinocytes at concentrations > 1 ng/ml. Calcipotriol and desoximetasone also showed a dose-dependent cell growth inhibition in epidermal cell cultures. IL-1 alpha synthesis was greatly suppressed by calcipotriol 10(-8)-10(-6) M. EGF at 10 ng/ml, in contrast, strongly stimulated IL-1 alpha production. Neither GDF-5 nor TGF-beta 1 had a significant effect on IL-1 alpha production in keratinocyte monolayer cultures. In fibroblasts, GDF-5 induced very weak antiproliferative effects. Calcipotriol and desoximetasone also inhibited cell growth in fibroblast cultures whereas proliferation and DNA synthesis were strongly stimulated by 1 ng/ml EGF. There was, however, a contradiction between TGF-beta 1 results on fibroblasts. Whereas TGF-beta 1 increased proliferation in cell number determination and in the thymidine incorporation assay, MTT assays showed slight antiproliferative effects. Due to these controversial results, in addition cell cycle analysis was employed. TGF-beta 1 led to an increased S phase, which indicates a stimulation of cell division. The different results obtained with the MTT test suggest that TGF-beta 1 may stimulate cell division of fibroblasts not only by increasing the S phase, but also by shortening the G1 phase of the cell cycle.

Cell Cycle↗
PubMed1998

Usual interstitial pneumonia: relationship between disease activity and the progression of honeycombing at thin-section computed tomography.

The authors estimate the relationship between the progression of honeycombing and disease activity of usual interstitial pneumonia (UIP) by open lung biopsy specimen and ground-glass opacity on thin-section computed tomography (CT). Open lung biopsy specimens and the initial and follow-up thin-section CT of 29 patients with proven UIP are reviewed. Follow-up thin-section CTs were performed from 2 to 61 months (mean, 15.3 months) after biopsy. The interval between the initial CT and open lung biopsy was from 2 to 30 days (mean, 10.0 days). Areas of ground-glass opacity and honeycombing were quantified respectively on each CT slice by using a 0%-100% scale with 10% increments. Each open lung biopsy specimen was scored semiquantitatively for alveolar desquamation, alveolar septal inflammation, inflammatory airway narrowing, obstructive pneumonitis, and lymphoid nodules. Patients were classified into either a mild or severe activity group according to the median value of the pathologic score and the median value of the area of ground-glass opacity. The authors compared the progression of honeycombing on follow-up thin-section CT between the groups. The progression of honeycombing in UIP was significantly faster in the severe activity group than in the mild group according to the pathologic score (p = 0.003) and the area of ground-glass opacity (p = 0.0024). In patients with UIP, more active inflammation of the pulmonary interstitium results in faster progression of honeycombing in long-term follow-up.

Adult↗