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Biomedical subjects

M K Kim

Publications and source records attributed to M K Kim.

At least 55 records · Page 3Linked to original sources

Formulation of a reservoir-type testosterone transdermal delivery system.

A reservoir-type transdermal delivery system of testosterone (TS) was developed using an ethanol/water (70:30) cosolvent system as the vehicle. The maximum permeation rate achieved by 70% (v/v) of ethanol was further increased from 2.69 to 47.83 microg/cm(2)/h with the addition of 1.0% dodecylamine as the skin permeation enhancer. The permeation rate of TS through the ethylene vinyl acetate (EVA) membrane was observed to increase as the vinyl acetate content in the copolymer increased. Addition of 1.0% (w/w) gelling agent, hydroxypropyl methlycellulose (HPMC), in the reservoir formulation resulted in desirable rheological properties with an insignificant effect on the skin permeation rate of TS. Thus, a new transdermal delivery system for TS was formulated using EVA membrane coated with a pressure-sensitive adhesive (Duro-Tak 87-2510) and HPMC as a gelling agent. This experimental patch showed comparable plasma concentration profiles in the in vivo study when compared with a commercial product, Androderm(R). Moreover, the results suggested the possibility of further enhancing the permeation rate of TS by controlling the composition of the reservoir formulation.

Administration, Cutaneous↗

The role of peripheral N-methyl-D-aspartate receptors in Freund's complete adjuvant induced mechanical hyperalgesia in rats.

We investigated the role of excitatory amino acid receptors in mechanical hyperalgesia induced by subcutaneous injection of Freund's complete adjuvant (FCA) into the rat hind paw. In normal rats, an intraplantar (i.pl.) injection of L-glutamate, but not of D-glutamate (3 pmol/0.1 ml each) produced a mechanical hyperalgesia in the hind paw with a lowered paw-withdrawal threshold to pressure. In rats that developed mechanical hyperalgesia associated with inflammation in the hind paw following i.pl. injection of FCA (0.15 ml), the injection of N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (1 pmol/0.1 ml) into the inflamed paw increased the paw pressure threshold. On the other hand, the injection of non-NMDA receptor antagonist, 6-cyano-7-nitroqiunoxaline-2,3-dione (CNQX, 10 pmol/0.1 ml) into the inflamed paw had no effect on FCA-induced lowering of the paw pressure threshold. The results suggest that NMDA, but not non-NMDA receptors play a substantial role in mediating the development of mechanical hyperalgesia induced in the inflamed paw following i.pl. FCA injection.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

CD99 regulates the transport of MHC class I molecules from the Golgi complex to the cell surface.

The down-regulation of surface expression of MHC class I molecules has recently been reported in the CD99-deficient lymphoblastoid B cell line displaying the characteristics of Hodgkin's and Reed-Sternberg phenotype. Here, we demonstrate that the reduction of MHC class I molecules on the cell surface is primarily due to a defect in the transport from the Golgi complex to the plasma membrane. Loss of CD99 did not affect the steady-state expression levels of mRNA and protein of MHC class I molecules. In addition, the assembly of MHC class I molecules and the transport from the endoplasmic reticulum to the cis-Golgi occurred normally in the CD99-deficient cells, and no difference was detected between the CD99-deficient and the control cells in the pattern and degree of endocytosis. Instead, the CD99-deficient cells displayed the delayed transport of newly synthesized MHC class I molecules to the plasma membrane, thus causing accumulation of the molecules within the cells. The accumulated MHC class I molecules in the CD99-deficient cells were colocalized with alpha-mannosidase II and gamma-adaptin in the Golgi compartment. These results suggest that CD99 may be associated with the post-Golgi trafficking machinery by regulating the transport to the plasma membrane rather than the endocytosis of surface MHC class I molecules, providing a novel mechanism of MHC class I down-regulation for immune escape.

12E7 Antigen↗

Variations of the prominences of the bony palate and their relationship to complete dentures in Korean skulls.

The osteological and morphological variations of the prominences in the bony palate of 160 Korean skulls were studied. The frequency of the occurrence of the posterior palatine crest, located on the posterior border of the greater palatine foramen, was 13.8%. Palatal ridges were observed commonly in the skulls; however, the smooth type, which has no palatal ridges in the palate, was shown in 14.7% of cases, and palatal spines were observed in 33.8%. The prevalence of palatal tubercles was 11.6%, and all were found in the molar region. The palatine torus was found in 18.8% of cases and the most common type was along the median palatine suture from the incisive foramen to the posterior border of the palatine bone (63.3%). No significant differences between sexes or sides were found in the posterior palatine crest, palatal ridges, and palatal tubercle. However, the sex distribution of the palatine torus was significantly different (P < 0.05). These results would be helpful clinically in fabricating maxillary complete dentures for edentulous patients.

Adult↗

Fine-needle aspiration cytology of pleuropulmonary blastoma: a case report with unusual features.

Pleuropulmonary blastoma (PPB) is a rare and aggressive intrathoracic neoplasm of childhood, typically presenting as a pulmonary and/or pleural-based mass with cystic, solid, or combined features. Histologically, the tumor is well characterized with a mixture of primitive mesenchymal and variably differentiated sarcomatous components, and the cytologic features described in the three previous reports are also compatible to the histologic ones. Now, we present another case of PPB showing unusual features. A 3-yr-old boy presented with a pleural- or chest wall-based tumor. The fine-needle aspiration cytologic smears were highly cellular with poorly differentiated cells showing variable size and shape rather than those of typical blastemal cells. The histologic findings were also distinctive, exhibiting diffuse sheets of poorly differentiated cells without typical blastemal cell component. Diagnosis was confirmed by the support of immunohistochemical and ultrastructural features. The patient underwent a typical aggressive clinical course to death within 8 mo after diagnosis.

Biomarkers, Tumor↗

Graded mode of transcriptional induction in yeast pheromone signalling revealed by single-cell analysis.

Signalling pathways typically convert a graded, analogue signal into a binary cellular output. In the several eukaryotic systems that have been investigated to date, including MAP kinase cascade activation in Xenopus oocytes, analogue-to-digital conversion occurs at points in the pathway between receptor activation and the effector mechanism. We used flow cytometry combined with an intracellular fluorescent reporter to examine the characteristics of the yeast pheromone-response pathway. Surprisingly, pheromone response in yeast, which relies on the MAP kinase cascade, behaved in a fundamentally graded manner. Expression of certain exogenous dominant inhibitors of the pathway converted the response to graded-or-none behaviour. These results have implications for the dissection of biological response mechanisms in cells and illustrate how signalling pathways, even homologous ones, may have strikingly different signal propagation/amplification characteristics.

Flow Cytometry↗

Fc gamma receptors differ in their structural requirements for interaction with the tyrosine kinase Syk in the initial steps of signaling for phagocytosis.

Receptors for the constant region of IgG, Fc gamma receptors, are expressed on the surface of hematopoietic cells, where they mediate signaling events, such as phagocytosis, essential for host defense. Fc gamma receptors also play a role in the pathophysiology of autoimmune diseases. We have demonstrated that members of each of the three classes of human Fc gamma receptors, Fc gamma RI, Fc gamma RII, and Fc gamma RIII, mediate phagocytosis, but that important differences exist in their requirements for phagocytic signaling. For example, the Fc gamma receptors Fc gamma RI and Fc gamma RIIIA induce signaling largely by association with a gamma subunit containing a conserved cytoplasmic motif (ITAM) whose tyrosines are phosphorylated following receptor stimulation. Fc gamma RIIA contains a similar motif in its own cytoplasmic domain and does not require the gamma chain for phagocytic signaling. The tyrosine kinase Syk associates with the cytoplasmic domain of both the Fc gamma receptor gamma chain and Fc gamma RIIA and is required for phagocytosis by both Fc gamma receptor systems. To elucidate the differences in phagocytic signaling by the gamma chain and Fc gamma RIIA, we investigated the requirements for Fc gamma receptor/Syk co-immunoprecipitation, tyrosine phosphorylation, and phagocytosis. Both Fc gamma RIIA and the human gamma chain contain a tyrosine seven amino acids upstream of the ITAM motif. We observed that the upstream tyrosine plays a role in Fc gamma RIIA phagocytic signaling but is not involved in phagocytic signaling by the human gamma chain. Our data also indicate that the two ITAM tyrosines of the human gamma chain and Fc gamma RIIA do not contribute equally to Fc gamma receptor association with Syk kinase and phagocytic signaling. The data indicate that the carboxy-terminal tyrosine of the receptor cytoplasmic domain is especially important both for the interaction with Syk kinase and for phagocytosis. Elucidating such differences in gamma chain and Fc gamma RIIA signaling may be valuable in designing strategies for therapeutic intervention in hematopoietic and immunological disorders.

Animals↗

Orientia tsutsugamushi suppresses the production of inflammatory cytokines induced by its own heat-stable component in murine macrophages.

Orientia tsutsugamushi is a Gram-negative obligate intracellular bacterium, which causes scrub typhus. To understand the pathogenesis of scrub typhus, we have investigated the induction of tumor necrosis alpha (TNF-alpha) and interleukin-6 (IL-6) by O. tsutsugamushi in two murine macrophage cell lines. Both live and heat-killed orientia stimulated the production of cytokines in J774A.1 cells. Polymyxin B does not affect the secretion of cytokines. These together with the fact that the immature macrophage cell line, P388D1, did not produce TNF-alpha when induced by either live or heat-killed O. tsutsugamushi strongly argue against any roles of lipopolysaccharide (LPS) in cytokine production. Furthermore, the result that the cytokine responses were more brisk when macrophage cell lines had been induced by heat-killed O. tsutsugamushi than by live organisms strongly suggest that a heat-stable molecule might be responsible for the induction of cytokine production and O. tsutsugamushi might have mechanisms suppressing the production of inflammatory cytokines induced by its own heat-stable molecule.

Animals↗

Exogenous peptide and protein expression levels using retroviral vectors in human cells.

Pseudotyped retroviral vectors combine the advantages of broad host range, high expression, stable chromosomal integration, and ease of preparation. These vectors greatly facilitate delivery into mammalian cells of sequences encoding individual peptide inhibitors-including those with therapeutic utility-and inhibitor libraries. However, retroviral vectors vary in behavior, particularly with respect to expression levels in different cell lines. Expression level is especially important in transdominant experiments because the concentration of an inhibitor (for example, an expressed peptide) is one of the key determinants in the degree of complex formation between the inhibitor and its target. Thus, inhibitor concentration should have an impact on the expressivity and/or penetrance of an induced phenotype. Here, we compare several retroviral vectors and human cell lines for relative expression levels using a green fluorescent protein reporter. We show for a subset of these lines that cellular protein concentrations produced by single-copy vectors range up to about 2 microM. We also examine other variables that contribute to expression level, such as the nature of the expressed protein's carboxy terminus. Finally, we test the effect of increased concentration on phenotype with a nine-amino-acid peptide derived from the human papilloma virus protein E7 which overcomes E7-mediated cell growth.

Animals↗

Cloning of the cel9A gene and characterization of its gene product from marine bacterium Pseudomonas sp. SK38.

The yellow-pigmented bacterial strain causing green spot rot and death of layer was isolated from Porphyra dentata. This strain has been identified as Pseudomonas sp., harboring agarase, xylanase, and protease activity, as well as carboxymethyl-cellulase (CMCase). Using genomic DNA from the Pseudomonas sp. SK38 digested with Sau3AI and ligated into pBluescript II KS+, we isolated a cel gene encoding a CMCase in Pseudomonas sp. SK38. A 4.5-kb fragment was subcloned into pKR400. The structure of the cel9A gene consists of an open reading frame of 1,521 bp starting with a GTG start codon and ending with a TAG stop codon. It thus encodes 506 amino acid residues of a protein with a calculated molecular weight of 52,636 daltons plus a signal peptide of 22 amino acids. The deduced amino acid sequence of the cel9A protein is similar to the same protein of Clostridium thermocellum. It contains, in particular, the two conserved regions of the glycoside hydrolase family 9. The apparent molecular mass of the Cel9A protein is 52 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme is most active at pH 6-7 and an optimal temperature of around 30 degrees C.

Amino Acid Sequence↗

Association between Helicobacter pylori infection and the risk of gastric cancer in the Korean population: prospective case-controlled study.

BACKGROUND: Gastric cancer is still the most common malignant tumor in Koreans. Although many reports have supported the association of Helicobacter pylori infection and the development of gastric cancer, few studies have been adjusted by variable factors such as age. sex, education, and economic status. Furthermore, most results from areas with a high incidence of gastric cancer, such as China and Korea, have failed to document any relationship between H. pylori infection and gastric cancer. We conducted a prospective case-controlled study, with controls matched for and adjusted by age, sex, education, and economic status, to evaluate the causal relationship between H. pylori infection and gastric cancer in Korean people. METHODS: From March 1997 to October 1998, 136 consecutive patients with gastric cancer, diagnosed by endoscopic histology, and 136 age- and sex-matched control subjects, confirmed to be free of gastric cancer by endoscopy during the same period, were enrolled in the study. The presence of H. pylori infection was determined by enzyme immunoassay (EIA) serology test. RESULTS: Seventy-two of the 136 gastric cancer patients (53%) were positive for H. pylori infection and 54 of the 136 control subjects (40%) were positive for H. pylori infection. The odds ratio (OR), adjusted by variable risk factors, such as age, sex, education, and economic status, for gastric cancer in H. pylori-infected patients was 1.82 (95% confidence internal [CI], 1.10-3.00; P = 0.019). The age- and sex-matched OR by conditional logistic regression was 1.6 (95% CI., 1.01-2.53; P = 0.043). CONCLUSIONS: H. pylori infection may be one of the important risk factors for the development of gastric cancer in Korea, an area of high prevalence of H. pylori infection and a high incidence of gastric cancer.

Adult↗

The mechanism of action of coculture on embryo development in the mouse model: direct embryo-to-cell contact and the removal of deleterious components.

OBJECTIVE: To elucidate the mechanism for the mode of action of coculture by the use of a coculture system for mouse one-cell embryos with human oviductal epithelial cells. DESIGN: Prospective, controlled in vitro experimental study. SETTING: Academic research laboratory. ANIMAL(S): Female ICR strain mice aged between 6 and 8 weeks. INTERVENTION(S): Flushed one-cell embryos were cultured in human tubal fluid medium alone (control), in coculture system with human oviductal cells, in five kinds of conditioned media, and in a contactless coculture system using a cell-culture insert. MAIN OUTCOME MEASURE(S): The percentage of the embryos developed to hatching blastocyst stage and the level of superoxide anion in the supernatant from each culture condition. RESULT(S): The rates of embryo development to the hatching blastocyst stage were significantly higher in the coculture group (43%) than in the control group (none) (P <.05). The embryo development rate in the control group was similar to that of the embryos in the five kinds of conditioned media. The effects of coculture on embryo development disappeared in the contactless coculture group. The level of superoxide anion was significantly reduced in the coculture group compared to the control group. CONCLUSION(S): The present coculture system overcomes the two-cell block in vitro and improves the embryo development. The beneficial effect may be a result of direct cell-to-cell contact between the embryo and helper cells and the removal of deleterious components from medium, rather than a result of embryotrophic factors.

Animals↗

Effect of poly(ethylene glycol) graft polymerization of poly(methyl methacrylate) on cell adhesion. In vitro and in vivo study.

PURPOSE: To investigate the effect of surface modification of poly(methyl methacrylate) (PMMA) by poly(ethylene glycol) (PEG) grafting on cell adhesion. SETTING: Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea. METHODS: The PMMA surface was oxidized with ozone, and PEG acrylate was then graft polymerized. To verify the PEG grafting on the surface, the oxygen content was measured by electron spectroscopy for chemical analysis. The contact angle was measured using the Wilhelmy plate method. The adhesion of keratocytes on modified PMMA was investigated in vitro. Cultured rabbit keratocytes (4 x10(5) cells/mL) were layered on each PMMA disk, cultured in a carbon dioxide incubator for 24 hours, harvested by trypsinization, and counted. A commercially available intraocular lens was modified as described and then inserted in the anterior chamber of a white rabbit. The cell adherence pattern on the modified IOL was examined by scanning electron microscopy. RESULTS: The PEG-grafted PMMA revealed a higher oxygen content and lower dynamic receding contact angles than the untreated PMMA. The mean number of adhered cells was 72.5 +/- 22 x 10(4)/mL for untreated PMMA. After PEG grafting of 1 hour and ozone oxidation of 2 hours, the adherent cell counts significantly decreased to 6.5 +/- 1.7 x 10(4)/mL and 7.6 +/- 1.6 x 10(4)/mL, respectively (P =.002). Scanning electron microscopy showed small round cells sparsely scattered on the modified PMMA in contrast to the untreated PMMA. CONCLUSION: Surface modification of PMMA using PEG grafting reduced cell adhesion. This may decrease the incidence of retroprosthetic membrane formation after keratoprosthesis surgery.

Animals↗

Selective growth inhibitor toward human intestinal bacteria derived from Pulsatilla cernua root.

Among 21 medicinal plants, the growth-inhibiting activity of Pulsatilla cernua root-derived materials toward human intestinal bacteria was examined by using an impregnated paper disk method. The biologically active components of P. cernua roots were characterized as 4-hydroxy-3-methoxycinnamic acid and 3,4-dihydroxycinnamic acid by spectroscopic analysis. The activity was compared with that of six commercially available cinnamic acid derivatives trans-cinnamaldehyde, trans-cinnamic acid, cinnamyl alcohol, 2-methoxycinnamic acid, 3-methoxycinnamic acid, and 4-methoxycinnamic acid. The growth responses varied with each bacterial strain tested. Two isolated compounds revealed a potent inhibition against Clostridium perfringens, and moderate to weak activity against Escherichia coli was exhibited by 4-hydroxy-3-methoxycinnamic acid. Weak or no inhibitory activity was obtained against the bifidobacteria or Lactobacillus acidophilus. The inhibitory effect was much more pronounced in C. perfringens and E. coli as compared to B. adolescentis, B. bifidum, B. fragilis, B. longum, or L. acidophilus. Cinnamaldehyde exhibited a strong growth-inhibiting activity, but no inhibition was observed from treatments with trans-cinnamic acid, cinnamyl alcohol, 2-methoxycinnamic acid, 3-methoxycinnamic acid, and 4-methoxycinnamic acid. These results may be an indication of at least one of the pharmacological actions of P. cernua root.

Acrolein↗

Frequency of cytochrome P450 2C9 mutant alleles in a Korean population.

AIMS: To determine the frequencies of CYP2C9 variants in the Korean population and compare them with the frequencies in other ethnic populations. METHODS: Genotyping of CYP2C9*2 and CYP2C9*3 allelic variants was carried out in 574 Korean subjects by PCR and restriction fragment length pattern analysis. RESULTS: Thirteen of 574 subjects (2.3%) were heterozygous for CYP2C9*3 (Ile359Leu), but no subjects with a CYP2C9*2 allele or homozygous for CYP2C9*3 were identified. The allele frequency of CYP2C9*3 in Korean subjects (0.0113, 95% CI 0.0066-0.0193) was similar to that of other East Asian populations, but was considerably lower than that of Caucasian populations. CONCLUSIONS: CYP2C9*3 seems to be an allelic variant related to the functional polymorphism of CYP2C9, but this variant is rarely seen among Koreans compared with Caucasians. Routine genotyping of the CYP2C9*2 allele is considered to be unnecessary in Korean and East Asians, because this allele appears to be extremely rare or absent in these populations.

Aryl Hydrocarbon Hydroxylases↗

Anatomical study of the pyramidal process of the palatine bone in relation to implant placement in the posterior maxilla.

The placement of dental implants in the molar region of the maxilla is often difficult because of insufficient bone volume and the inferior bone quality. In order to avoid these limitations, the pillar of bone, which is composed of the maxillary tuberosity, the pyramidal process of the palatine bone and the pterygoid process of the sphenoid bone, was introduced for implant placement. In fact, the pyramidal process is the posterior structure where implants are placed but until now, there is no available data of the size or shape of the pyramidal process. Therefore, we measured the height, anteroposterior distance and mediolateral distance of the pyramidal process and observed the shape of lateral and posterior surfaces of the pyramidal process of 54 Korean edentulous dry skulls in this study. The height was 13.1 mm (male: 13.6 mm, female: 12.4 mm). The anteroposterior distance was 6.5 mm (male: 6.7 mm, female: 6.1 mm). The mediolateral distance was 9.5 mm (male: 9.9 mm, female: 9.0 mm). The most common type was the right-angled triangle in the lateral surface (44.4%) and in the posterior surface (66.7%). There was no statistical significance between the male and the female in all items (P > 0.05). These results provide anatomical features in relation to placement of dental implants in the molar region of the maxilla and would be useful in treatment planning of partially or completely edentulous patients.

Aged↗

Pathogenic significance of neuronal migration disorders in temporal lobe epilepsy.

To assess the epileptogenic lesions, a series of 202 cases with temporal lobectomy were analyzed histopathologically. The severity of hippocampal neuronal loss in patients with temporal lobe epilepsy was quantitatively analyzed and compared against autopsy controls of patients who died of nonneurologic disorders. For the histopathologic diagnosis of neuronal migration disorder (NMD), immunohistochemical stains for neurofilament protein (NF-M/H) and microtubule-associated protein 2 (MAP2) and Bielschowsky silver stains were routinely performed. Histopathology of NMD was classified by the 4-grade system. MAP2 immunoreactivity was useful in the identification of loss of normal polarization of dendrites in the abnormal neurons. NF-M/H immunohistochemistry and silver stains effectively labeled microscopic or occult lesions of NMD (grade II and III). Ammon hom sclerosis (AHS) was identified in 73.3% and NMD in 57.9%. There was more than 50% neuronal cell loss in 82.8% of AHS, and variable degrees of cell loss were observed in the dual-pathology groups. The frequency of dual pathology (both AHS and NMD) was 65.0% and showed relatively equal distributions in grades I, II, III, whereas the pure NMD group were classified predominantly as grades II and III. NMD might be a basic pathogenic substrate causing temporal lobe epilepsy. The dual pathology may indicate the presence of epileptogenic lesions in the neocortical and temporolimbic areas.

Brain Neoplasms↗

Isolation of virus-cell fusion inhibitory components from Eugenia caryophyllata.

The fractionation of Eugenia caryophyllata (Myrtaceae) guided by the syncytia formation inhibition assay led to the isolation of four tannins (eugeniin, casuarictin, 1,3-di-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-beta-D-glucopyranose, and tellimagrandin I), and two chromones (biflorin and isobiflorin). Among the isolated compounds, tellimagrandin (4) showed a significantly high inhibitory activity on the syncytia formation with an IC50 value of 16.12 +/- 1.98 micrograms/ml.

Chromones↗