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Biomedical subjects

E J Kim

Publications and source records attributed to E J Kim.

At least 91 records · Page 5Linked to original sources
PubMed2000

Gastrointestinal first-pass effect of furosemide in rats.

The first-pass effect of furosemide was investigated in rats. Furosemide intravenous solution (20 mg kg(-1) Lasix), was administered via the jugular vein and the portal vein, orally, and instilled directly into the duodenum of rats. The first-pass effects of furosemide by lung, heart, and liver seemed to be negligible in rats. The absolute bioavailability of furosemide was 28.9 and 48.3% after oral and intraduodenal administration, respectively. Based on the gastrointestinal (GI) recovery study, 68.3 and 69.5% of furosemide were found to have disappeared mainly due to absorption and/or metabolism from rat GI tract after oral and intraduodenal administration, respectively. The results indicate that gastrointestinal and intestinal first-pass effects of furosemide were approximately 40% (68.3-28.9%) and 20% (69.5-48.3%) of the dose, respectively.

Administration, Oral↗
PubMed2000

Morphologic change of the internal elastic lamina in Buerger's disease.

Morphologic features and pathogenesis of arterial changes occurring in Buerger's disease (thromboangiitis obliterans) are still controversial. This study describes histopathologic features of medium sized arteries from patients with Buerger's disease, particularly of the internal elastic lamina in relation to the immunologic mechanism of the injury. Seventeen segments of occluded arteries (femoral or popliteal arteries) from 17 patients with Buerger's disease were analyzed by histopathological and immunohistochemical methods. The most characteristic features were total luminal obliteration, together with a varying degree of recanalization and deposition of hemosiderin pigments. Detailed analysis, however, showed marked undulation and multiplication of the internal elastic lamina (100%) associated with basophilic degeneration and delicate linear calcification (47%). Lymphocytic infiltration along the internal elastic lamina was seen in 71% and was associated with localized edema. Lymphocytes along the lamina were consistently positive for T cell marker. Mild to moderate fibrosis was present at the media in 24%. Adventitial changes included mild, nonspecific and irregular fibrosis seen in 53%. Immunologic injury to the internal elastic lamina associated with T-lymphocytic infiltration might be the initial morphogenetic mechanism of the thrombotic occlusion and organization of medium-sized arteries in Buerger's disease.

Adult↗
PubMed2000

Clinical correlations of peripheral blood microchimerism after liver transplantation.

The aim of this study was to evaluate microchimerism after human liver transplantation (LT). This study included 13 female recipients who received hepatic allograft from male donors at Asan Medical Center. A nested PCR specific for Y-chromosome gene (DYZ3) was used to analyze the small number of male cells in the peripheral blood mononuclear cells of the female recipients. Microchimerism was observed in 6 of 13 recipients and 16 out of 35 samples. Only 3 patients showed microchimerism 3 months after LT. There was no statistical difference between the presence of microchimerism and clinical findings such as type of donor, type of immunosuppression, episode of rejection and age of recipient. This study did not show any clinical relevance of microchimerism and further larger study are needed to confirm the results.

Adolescent↗
PubMed2000

Estrogen affects vascular tone differently according to vasoactive substances in ovariectomized Sprague-Dawley rat.

The favorable effects of estrogen on cardiovascular diseases can be explained by several mechanisms such as changes in serum lipid profiles and thrombogenecity. Estrogen also affects the vascular tone, but there has been no report in which the effect of estrogen was tested comprehensively for several vasoactive substances, especially after long-term administration. Two weeks after bilateral ovariectomy in 8-week old female Sprague-Dawley rats, placebo or 17 beta-estradiol (E2) pellets (0.5 mg; released over 3 weeks) were implanted subcutaneously. Two weeks after pellet implantation, organ chamber experiments were performed using aortae. Compared with control, E2-treated vessels showed impaired endothelium-dependent relaxation to acetylcholine. E2 enhanced the contraction to norepinephrine and U46619 and had no effect on endothelin-1-induced contraction. In contrast, the contraction to angiotensin (AT)-II was inhibited by E2. Northern blot analysis for AT1 receptor expression using cultured aortic smooth muscle cells showed no difference between control and E2-treated cells, suggesting that AT1 receptor downregulation is not the likely mechanism. These results suggest that E2 affects the vascular tone variably according to vasoactive substances.

Animals↗
PubMed1999

Autologous transplantation of bone marrow cells improves damaged heart function.

BACKGROUND: Autologous bone marrow cells (BMCs) transplanted into ventricular scar tissue may differentiate into cardiomyocytes and restore myocardial function. This study evaluated cardiomyogenic differentiation of BMCs, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function. METHODS AND RESULTS IN VITRO STUDIES: BMCs from adult rats were cultured in cell culture medium (control) and medium with 5-azacytidine (5-aza, 10 micromol/L), TGFbeta1 (10 ng/mL), or insulin (1 nmol/L) (n=6, each group). Only BMCs cultured with 5-aza formed myotubules which stained positively for troponin I and myosin heavy chain. In vivo studies: a cryoinjury-derived scar was formed in the left ventricular free wall. At 3 weeks after injury, fresh BMCs (n=9), cultured BMCs (n=9), 5-aza-induced BMCs (n=12), and medium (control, n=12) were autologously transplanted into the scar. Heart function was measured at 8 weeks after myocardial injury. Cardiac-like muscle cells which stained positively for myosin heavy chain and troponin I were observed in the scar tissue of the 3 groups of BMC transplanted hearts. Only the 5-aza-treated BMC transplanted hearts had systolic and developed pressures which were higher (P<0.05) than that of the control hearts. All transplanted BMCs induced angiogenesis in the scar. CONCLUSIONS: Transplantation of BMCs induced angiogenesis. BMCs cultured with 5-aza differentiated into cardiac-like muscle cells in culture and in vivo in ventricular scar tissue and improved myocardial function.

Animals↗
PubMed1999

Cyclooxygenase-2 selective inhibitors aggravate kainic acid induced seizure and neuronal cell death in the hippocampus.

Cyclooxygenase-2 (COX-2) in the brain is expressed constitutively and also increased in pathological conditions such as seizure, cerebral ischemia, and inflammation. This study examined the role of COX-2 in kainic acid-induced seizure and in the following neuronal death by using selective inhibitors. Systemic kainate injection (50 mg/kg; i.p.) in mice evoked seizure within 15 min and led to 29% mortality within 2 h. TUNEL-positive neuronal death peaked at 3 days after injection and was prominent in CA(3a) regions of the hippocampus. NS-398 or celecoxib (10 mg/kg, COX-2 selective inhibitor) and indomethacin (5 mg/kg, nonselective inhibitor) exaggerated kainic acid-induced seizure activity and mortality. COX-2 selective inhibitors induced the seizure at earlier onset and more severe mortality within the first hour than indomethacin and aspirin. NS-398 also aggravated kainic acid-induced TUNEL positive neuronal death and decreased Cresyl violet stained viable neurons, and extended lesions to CA(1) and CA(3b). Kainic acid increased the levels of PGD(2), PGF(2a) and PG E(2) in the hippocampus immediately after injection. Indomethacin attenuated the production of basal and kainic acid-induced prostaglandins. In contrast, NS-398 failed to reduce until the first 30 min after kainic acid injection, during which the animals were severely seizured. It has been challenged the endogenous PGs might have anticonvulsant properties. Thus, COX-2 selective inhibitor, including nonselective inhibitor such as indomethacin, aggravated kainic acid-induced seizure activity and the following hippocampal neuronal death even with variable prostaglandin levels.

Animals↗
PubMed1999

Transient upregulation of osteopontin mRNA in hippocampus and striatum following global forebrain ischemia in rats.

We investigated the spatial and temporal expression of osteopontin (OPN) mRNA following transient forebrain ischemia in rats. Experiments were carried out using a four-vessel occlusion model for forebrain ischemia. The transient induction of OPN mRNA after global ischemia occurred earlier in the striatum than in the hippocampus. It was pronounced in the dorsomedial striatum close to the lateral ventricle and in the CA1 subfield and the subiculum of the hippocampus before microglial cells became more reactive. It also could be detected in the dentate hilus and to a marginal extent in the CA3. Our results suggest that the hippocampus and the striatum following global forebrain ischemia upregulate OPN mRNA in different spatiotemporal profiles.

Animals↗
PubMed1999

Antigen-specific cytotoxicity and cell number of adoptively transferred T cells are efficiently maintained in vivo by re-stimulation with an antigen/interleukin-2 fusion protein.

In order to maintain in vivo anti-tumor efficacy of antigen (Ag)-specific T cells in adoptive immunotherapy for a prolonged period, we constructed a fusion protein (OVA/IL-2) containing ovalbumin (OVA) as a model tumor Ag, co-valently linked to murine interleukin-2 (IL-2). The OVA/IL-2 protein produced in a baculovirus expression system displayed potent IL-2 bio-activity. Immunization with the OVA/IL-2 protein after adoptive transfer of OVA-specific T cells maintained the OVA-specific cytotoxicity and cell number of adoptively transferred T cells long term in vivo, while a simple mixture of recombinant OVA (rOVA) and rIL-2 did not. The response was dependent on the injection doses and times of the OVA/IL-2 protein. Furthermore, weekly re-stimulation of adoptively transferred OVA-specific T cells with the OVA/IL-2 protein cured 70% of tumor-bearing mice. In contrast, re-stimulation with a mixture of rOVA and rIL-2 could not significantly prolong the survival period of tumor-bearing mice. These studies suggest that the co-valent linkage between IL-2 and antigen confines the effect of IL-2 to antigen-specific T cells, leading to efficient maintenance of the anti-tumor activity of adoptively transferred T cells.

Animals↗
PubMed1999

Distinct responses of a recA::luxCDABE Escherichia coli strain to direct and indirect DNA damaging agents.

The recombinant Escherichia coli strain DPD2794 containing a recA::luxCDABE fusion is used to detect genotoxicity of various chemicals. Genotoxic agents were previously categorized into two groups, Direct DNA Damaging (DDD) agents and Indirect DNA Damaging (IDD) agents; these two groups have been distinguished with this strain. Minimum detectable concentrations of the DDD agents were about one to five orders of magnitude lower than those of the IDD agents. The response patterns of this strain to DDD agents differed from those to IDD agents in terms of kinetics and the forms of the dose-dependent response.

DNA Damage↗
PubMed1999

Tolerance to toxic metals by a gene family of phytochelatin synthases from plants and yeast.

Phytochelatins play major roles in metal detoxification in plants and fungi. However, genes encoding phytochelatin synthases have not yet been identified. By screening for plant genes mediating metal tolerance we identified a wheat cDNA, TaPCS1, whose expression in Saccharomyces cerevisiae results in a dramatic increase in cadmium tolerance. TaPCS1 encodes a protein of approximately 55 kDa with no similarity to proteins of known function. We identified homologs of this new gene family from Arabidopsis thaliana, Schizosaccharomyces pombe, and interestingly also Caenorhabditis elegans. The Arabidopsis and S.pombe genes were also demonstrated to confer substantial increases in metal tolerance in yeast. PCS-expressing cells accumulate more Cd2+ than controls. PCS expression mediates Cd2+ tolerance even in yeast mutants that are either deficient in vacuolar acidification or impaired in vacuolar biogenesis. PCS-induced metal resistance is lost upon exposure to an inhibitor of glutathione biosynthesis, a process necessary for phytochelatin formation. Schizosaccharomyces pombe cells disrupted in the PCS gene exhibit hypersensitivity to Cd2+ and Cu2+ and are unable to synthesize phytochelatins upon Cd2+ exposure as determined by HPLC analysis. Saccharomyces cerevisiae cells expressing PCS produce phytochelatins. Moreover, the recombinant purified S.pombe PCS protein displays phytochelatin synthase activity. These data demonstrate that PCS genes encode phytochelatin synthases and mediate metal detoxification in eukaryotes.

Amino Acid Sequence↗
PubMed1999

Transdermal scopolamine alters phasic REM activity in normal young adults.

Transdermal scopolamine has been widely used for the prevention of motion-sickness by travelers due to its potent anticholinergic effects and the ease of administration. Nevertheless, its effects on sleep physiology are not known, despite the wellknown fact that the administration of scopolamine as an injection or an oral form could influence the sleep architecture, especially prolonging rapid eye movement (REM) sleep latency and shortening duration of REM sleep. This study aimed to measure the influence of transdermal scopolamine on REM sleep in order to examine whether it affects REM sleep as in the previous studies. We studied eight young healthy male adults polysomnographically for three nights including one adaptation night in a double blind crossover design and compared REM sleep-related variables between sleeps with and without scopolamine patch of 1.5 mg. We found no differences in tonic REM sleep measures such as REM duration and REM latency, but phasic REM sleep measures such as total REM activity (p < 0.05) and total REM density (p < 0.05) were significantly suppressed by the transdermal scopolamine; REM densities of the first (p < 0.05) and the second (p < 0.05) REM sleep periods as well as REM activity of the fourth REM sleep period (p < 0.05) were decreased significantly on the scopolamine patch nights compared with placebo patch nights. These results suggest that phasic REM components reflect cholinergic mechanism in the central nervous system (CNS) even at the lowest commercial dose, and could be useful markers of CNS cholinergic activities in the future research.

Adult↗
PubMed1999

Duplicate genes for Fe-containing superoxide dismutase in Streptomyces coelicolor A3(2).

Streptomyces coelicolor Müller contains two types of superoxide dismutase (SOD) containing Ni (encoded by sodN) or Fe (encoded by sodF). Unlike a single species of Fe-containing SOD in Müller strain, multiple forms of FeSODs were detected in S. coelicolor A3(2) strain by activity staining and Western blot analysis. Genomic Southern hybridization suggested the presence of at least two copies of the sodF-like gene in A3(2). Two different genes for FeSOD (sodF1 and sodF2) were isolated from the phage library of A3(2) genome. The nucleotide sequence of the sodF1 coding region was identical with the unique sodF gene from Müller while that of sodF2 shared 88% identity. The gene products of sodF1 and sodF2 were identified by activity staining and immunoblot analysis. Expression from the sodF1 gene was repressed by nickel as sensitively as Müller sodF, suggesting the presence of Ni-responsive regulatory site within the region shared by the two genes. Among 12 other Streptomyces species examined, only S. fradiae contained two FeSOD-like polypeptides. We postulate that the additional copy of the sodF gene (sodF2) was provided by the horizontal transfer from remotely related bacteria.

Amino Acid Sequence↗
PubMed1999

Development of a serum-free medium for the production of erythropoietin by suspension culture of recombinant Chinese hamster ovary cells using a statistical design.

In order to develop a serum-free (SF) medium for the production of erythropoietin (EPO) by suspension culture of recombinant Chinese hamster ovary (rCHO) cells, a statistical optimization approach based on a Plackett-Burman design was adopted. A basal medium was prepared by supplementing Iscove's modified Dulbecco's medium (IMDM) with Fe(NO3)3.9H2O, CuCl2 and ZnSO4.7H2O which are generally contained in SF medium formulations. Insulin, transferrin and ethanolamine were also supplemented to the basal medium to determine their optimal concentrations. From this statistical analysis, glutamate, serine, methionine, phosphatidylcholine, hydrocortisone and pluronic F68 were identified as positive determinants for cell growth. The SF medium was formulated by supplementing the basal medium with components showing positive effects on cell growth in suspension culture. An EPO titer in this optimized SF medium was 79% of that in IMDM supplemented with 5% dialyzed fetal bovine serum (dFBS). Furthermore, the in vitro and in vivo biological activities of EPO produced in the SF medium were comparable to those produced in the serum-supplemented medium. Taken together, the results obtained here show that a Plackett-Burman design facilitates the development of SF media for the production of EPO by suspension culture of rCHO cells.

Animals↗
PubMed1999

Inhibition of lipopolysaccharide-induced inducible nitric oxide (iNOS) mRNA expression and nitric oxide production by higenamine in murine peritoneal macrophages.

Nitric oxide synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation in rheumatic and autoimmune diseases. The effects of higenamine, a tetrahydroisoquinoline compound, on induction of NOS by bacterial lipopolysaccharide (LPS) were examined in murine peritoneal macrophages. LPS-induced nitrite/nitrate production was markedly inhibited by higenamine which at 0.01 mM, decreased nitrite/nitrate levels by 48.7+/-4.4%. This was comparable to the inhibition of LPS-induced nitrite/nitrate production by tetrandrin (49.51+/-2.02%) at the same concentration. Northern and Western blot analysis of iNOS expression demonstrated that iNOS expression was significantly attenuated following co-incubation of peritoneal macrophages with LPS (10 microg/ml; 18 hrs) and higenamine (0.001, 0.01 mM; 18 hrs). These results suggest that higenamine can inhibit LPS-induced expression of iNOS mRNA in murine peritoneal macrophages. The clinical implications of these findings remain to be established.

Alkaloids↗
PubMed1999

Neurilemmoma of the mandible.

Intraosseous neurilemmoma is rare, representing less than 1% of benign primary bone tumors. The site most commonly involved is the mandible. We report on a neurilemmoma of the mandible in a 30-year-old woman. A panoramic radiograph of the mandible showed a well-defined unilocular osteolytic lesion with a thin uniform sclerotic margin located in the body of the mandible. The CT scan confirmed a well-defined osteolytic lesion with thinning of the cortex of the body of the left side of the mandible. Histologically, the lesion was a moderately cellular neoplasm with distinct palisading and numerous Verocay bodies. Ultrastructurally, the cytoplasmic membranes were distinct and coated by amorphous bands of basal lamina. Complete excision was achieved by removing the tumor from the inferior alveolar nerve.

Adult↗
PubMed1999

Development of a serum-free medium for dihydrofolate reductase-deficient Chinese hamster ovary cells (DG44) using a statistical design: beneficial effect of weaning of cells.

To develop serum-free (SF) medium for dihydrofolate reductase-deficient Chinese hamster ovary cells (DG44), a statistical optimization approach based on a Plackett-Burman design was adopted. DG44 cells which were normally maintained in 10 serum medium were gradually weaned to 0.5% serum medium to increase the probability of successful growth in SF medium. A basal medium was prepared by supplementing Dulbecco's modified Eagle's medium and Ham's nutrient mixture F12 with hypoxanthine (10 mg/l) and thymidine (10 mg/l). Twenty-eight different supplements were selected as variables on the basis of their growth-promoting abilities. From statistical analysis, leucine, tryptophan, lysine, proline, histidine, hydrocortisone, ethanolamine, and phosphatidylcholine were identified as important components showing positive effects on cell growth. A new SF medium (SF-DG44) was formulated by supplementing the basal medium with these components. When the weaned cells were inoculated at 1.0 x 10(5) cells/ml, a maximum viable cell concentration of 6.4 x 10(3)) cells/ ml was achieved in SF-DG44 medium. In contrast, when the unweaned cells were used, a concentration of only 4.1 x 10(5) cells/ml was reached under the same culture conditions, indicating that weaning of cells improves cell growth in SF medium. In summary, we found that development of a novel SF medium for DG44 cells was facilitated using a Plackett-Burman design technique and weaning of cells.

Animals↗
PubMed1999

Autologous heart cell transplantation improves cardiac function after myocardial injury.

BACKGROUND: Fetal ventricular cardiomyocyte transplantation into a cardiac scar improved ventricular function, but these cells were eventually eliminated by rejection. We therefore examined the feasibility of autologous adult heart cell transplantation. METHODS: A transmural scar was produced in the left ventricular free wall of adult rats by cryoinjury. The left atrial appendage was harvested, and the atrial heart cells were cultured and their number expanded ex vivo. Three weeks after cryoinjury, either a cell suspension (2 x 10(6) cells, n = 12 rats, transplant group) or culture medium (n = 10 rats, control group) was injected into the scar. Rats having a sham operation (n = 5) did not undergo cryoinjury or transplantation with cells or culture medium. RESULTS: Five weeks after injection, ventricular function was evaluated in a Langendorff preparation, measuring systolic, diastolic, and developed pressures over a range of intraventricular balloon volumes. Systolic and developed pressures were greater in the transplant group than in the control group (p = 0.0001). Rats with a sham operation had the greatest systolic, diastolic, and developed pressures (p = 0.0001). Histologic studies demonstrated survival of the transplanted heart cells within the scar. The area of the scar was smaller (p = 0.0003) and its thickness greater (p = 0.0003) in rats in the transplant group. Left ventricular chamber volume was smaller in the transplant group (p = 0.043). CONCLUSIONS: Transplantation of autologous cultured adult atrial heart cells limited scar thinning and dilatation and improved myocardial function compared with results in control hearts. This technique may lead to a novel therapy to prevent scar expansion after a myocardial infarction and prevent the development of congestive heart failure.

Animals↗