Biomedical subjects

D S Kim

Publications and source records attributed to D S Kim.

At least 163 records · Page 9Linked to original sources

PubMed1999

Genomic organization and sequence of the mud loach (Misgurnus mizolepis) growth hormone gene: a comparative analysis of teleost growth hormone genes.

The mud loach (Misgurnus mizolepis) growth hormone (GH) gene was cloned and a comparative analysis on its genomic organization was performed. Based on Southern analysis using various kinds of restriction endonucleases, the GH gene proved to exist as a single-copy gene in the mud loach. The complete nucleotide sequences of a 5.1 kb SacI/EcoRI genomic fragment containing the mud loach GH gene and its 5' flanking sequences as well as a mud loach GH cDNA obtained by rapid amplification of a reverse transcriptase-PCR have been determined. The GH gene spans 2.0 kb from the start codon to the polyadenylation signal, and contains five exons and four introns similar to those of carps and mammals. The evolutionary relation of the mud loach GH gene, inferred by comparative analyses of gene structures and sequences in each exon and intron of representative teleost GH genes, reflects the major phylogenetic groupings of teleost.

Amino Acid Sequence↗

PubMed1999

Enhanced hepatocyte uptake and liver targeting of methotrexate using galactosylated albumin as a carrier.

Liver targeting of drugs has wide therapeutic implications due to numerous liver-related diseases. Using conjugates of methotrexate (MTX) to variously galactosylated bovine serum albumin (BSA), we studied whether we could enhance the liver targeting of MTX, a model drug, via galactose receptors selectively abundant on the hepatocytes. Here, we report that the galactosylation of the carrier protein BSA significantly enhanced the hepatocyte uptake and liver targetability of MTX. In vitro, the amount of MTX taken up by rat hepatocytes was positively correlated with the galactose content in BSA. MTX conjugates were relatively stable in plasma, but released MTX with time in liver homogenates. These results imply that the conjugates would exert low toxicity in the blood, but have therapeutic activity in the liver by liberating MTX. In vivo, MTX-galactosylated BSA conjugates (MTX-L(24)BSA) showed significantly different pharmacokinetics from free MTX or MTX-BSA conjugates. The plasma level of free MTX rapidly declined in a biexponential fashion with an apparent terminal half-life of 0.35 h. MTX-BSA conjugates showed the slowest decline with an apparent terminal half-life of 6 h, whereas MTX-L(24)BSA showed a biphasic pattern; a rapid distributive phase with a half-life of 0.567 h and a slow terminal phase. MTX-L(24)BSA showed the highest liver targetability, when evaluated in terms of two indices based on the area under the total amount of radioactivity-time curve (AUQ); Te*(liver), % AUQ(liver) to total AUQ, and te*, the ratio of AUQ(liver) to AUQ(kidney). Compared with free MTX and MTX-BSA, MTX-L(24)BSA showed about twofold higher Te*(liver) of 87.5%. The te* of MTX-L(24)BSA was 25- and fourfold higher than those of free MTX and MTX-BSA, respectively. Moreover, MTX-L(24)BSA showed a gradual increase in the therapeutically active intact form of MTX in the liver while showing the lowest level of intact MTX in the kidney. These results suggest that galactosylated BSA has a great potential as an hepatocyte-directed and more effective liver targeting carrier of drugs for liver diseases.

Animals↗

PubMed1999

Feeding behavior in dopamine-deficient mice.

Mice that cannot make dopamine (DA), a condition caused by the selective inactivation of tyrosine hydroxylase in dopaminergic neurons, are born normal but gradually become hypoactive and hypophagic, and die at 3 weeks of age. We characterized the feeding and locomotor responses of these DA-deficient (DA-/-) mice to 3, 4-dihyroxy-L-phenylalanine (L-DOPA) to investigate the relationship between brain DA levels and these complex behaviors. Daily administration of L-DOPA to DA-/- mice stimulated locomotor activity that lasted 6 to 9 hr; during that time the mice consumed most of their daily food and water. The minimal dose of L-DOPA that was sufficient to elicit normal feeding behavior in the DA-/- mice also restored their striatal DA to 9.1% of that in the wild-type (WT) mice at 3 hr; then DA content declined to <1% of WT levels by 24 hr. This dose of L-DOPA induced locomotor activity that exceeded that of treated WT mice by 5- to 7-fold, suggesting that DA-/- mice are supersensitive to DA. Unexpectedly, DA-/- mice manifested a second wave of activity 24 to 48 hr after L-DOPA treatment that was equivalent in magnitude to that of WT mice and independent of DA receptor activation. The DA-/- mice approached, sniffed, and chewed food during this second period of activity, but they ate <10% of that required for sustenance. Therefore, DA-/- mice can execute behaviors necessary to seek and ingest food, but they do not eat enough to survive.

Animals↗

PubMed1999

Expression of mRNAs encoding full-length and truncated TrkB receptors in rat dorsal root ganglia and spinal cord following peripheral inflammation.

Peripheral inflammation induces an increased brain-derived neurotrophic factor (BDNF) synthesis in the dorsal root ganglion (DRG) and an elevated anterograde transport of BDNF to axon terminals in the spinal dorsal horn. To characterize whether expression of trkB is modulated in response to BDNF elevation in these areas, we evaluated changes in expression of full-length and truncated trkB (trkB.FL and trkB.T) mRNAs after injection of complete Freund's adjuvant into the hind paw of the rat. Reverse transcription-polymerase chain reaction analysis revealed that BDNF and trkB.T mRNAs levels in the DRG increased, while no change of expression of trkB.FL mRNA was observed. There was no detectable change in both trkB.FL and trkB.T mRNAs levels in the spinal cord. Considering that trkB.T mRNA is expressed mainly in the perineuronal satellite cells, these results suggest a possible paracrine role of BDNF within the DRG in addition to an important role related with nociception following peripheral inflammation.

Animals↗

PubMed1999

Expression of the HMGI(Y) gene in human colorectal cancer.

Expression of HMGI(Y), a nucleoprotein that binds to A/T rich sequences in the minor groove of the DNA helix, is observable in neoplastically transformed cells but not in normal cells. We have analyzed HMGI(Y) expression in colorectal cancer and evaluated its clinicopathologic significance. HMGI(Y) mRNA was measured by CRT-PCR (competitive reverse transcription-polymerase chain reaction). Immunohistochemical staining for HMGI(Y), p53 and Ki-67 was performed in the same colon cancer tissues, and the results in colorectal tissues were similar to those of RT-PCR. HMGI(Y) expression evidenced by RT-PCR was observed in 63 of 64 (98.4%) colorectal cancer samples, and 2 of 5 (40%) adenomatous polyps, whereas 21 normal colon samples were negative (p<0.001). High HMGI(Y) expression using CRT-PCR was found in colon cancers with a high Ki-67 labeling index (p<0.001). There was no significant correlation between the levels of HMGI(Y) expression and stage, tumor size, lymph node metastasis, histologic grade and immunohistochemical status of p53. Our results indicate that the HMGI(Y) expression may occur at an early stage of carcinogenesis and correlate with cell proliferation. Int. J. Cancer (Pred. Oncol.), 84:376-380, 1999.

Adenomatous Polyposis Coli↗

PubMed1999

Geometrical and topological relationships between multiple functional maps in cat primary visual cortex.

The mammalian striate cortex is organized such that the receptive field properties of neighboring neurons change gradually across the cortical surface, forming so-called cortical maps. The presence of such maps has been demonstrated in different species of mammals for several parameters characterizing the visual space: retinotopy, ocular dominance, orientation, direction of motion and spatial frequency. In this study we used the optical imaging of intrinsic signals to simultaneously record the multiple functional maps in the same animal in order to obtain a comprehensive set of rules that govern mutual dependencies among the functional maps. Our results indicate that while orientation, direction and ocular dominance are represented on the cortex in a mutually dependent manner, the representation of spatial frequency is independent of the other types of cortical representations. The presence and/or absence of mutual dependence among the multiple functional maps are suggested to provide an important clue for the understanding of the development of visual cortical information representation in neonatal animals.

Animals↗

PubMed1999

A novel disintegrin salmosin inhibits tumor angiogenesis.

Salmosin is a snake venom-derived novel disintegrin that antagonizes platelet aggregation. In this study, we investigated its functional specificity in tumor angiogenesis. Salmosin significantly inhibited bovine capillary endothelial cell proliferation induced by basic fibroblast growth factor but had no effect on normal growth of the cell. The basic fibroblast growth factor-induced in vivo angiogenesis in the chorioallantoic membrane was disrupted by salmosin treatment without affecting normal embryonic angiogenesis. Adhesion of the bovine capillary endothelial cells to vitronectin was also inhibited by the binding of salmosin to the alpha(v)beta3 integrin. Both the metastatic-tumor growth and the solid-tumor growth that developed in mice were effectively suppressed by salmosin treatment. Several lines of experimental evidence strongly suggest that the tumor-specific antiangiogenic activity of salmosin disrupts tumor growth by blocking the alpha(v)beta3 integrin that is expressed on the vascular endothelial cell surface.

Allantois↗

PubMed1999

Semisynthesis of abrusoside A methyl ester.

Abrusoside A methyl ester was prepared from abrusogenin through methylation (CH2N2) and a subsequent coupling reaction with 1-chloro-2,3,4,6-tetra-O-acethylglucopyranose in the presence of AgOTf and TMU in CH2Cl2, followed by deacetylation using K2CO3 in MeOH-H2O.

Plants, Medicinal↗

PubMed1999

cDNA cloning of the CEPUS, a secreted type of neural glycoprotein belonging to the immunoglobulin-like opioid binding cell adhesion molecule (OBCAM) subfamily.

GP55 is a family of glycoproteins distributed predominantly in the nervous system, and its previously characterized members, including the GP55A (EMBL Y08170) and E19S (EMBL Y08171) reveal a typical glycosyl phosphatidyl inositol (GPI)-anchored pattern for membrane proteins. CEPUS identified in this study appeared to represent the third member of GP55. This 3.2 kb long complete cDNA clone from the chicken brain exhibited 3 Ig-like domains. The open reading frame of CEPUS contains 313 amino acids, which can encode a 31.7 kDa core protein (pI 5.75) for the mature form. The signal peptide cleavage site was predicted at Gln25. The structural features of the CEPUS cDNA sequence represented a soluble counterpart to the recently identified cerebellar Purkinje cell specific antigen, CEPU-1. The sequence difference between CEPU-1 and CEPUS was only found in the C-terminus in which the CEPUS lacked the GPI-anchored binding site. It displays significant sequence homology to GP55-related molecules, including OBCAM, GP55A, E19S/LAMP, neurotrimin, and CEPU-1, which are all membrane attached types. The absence of the hydrophobic tail sequence in CEPUS may, therefore, suggest that CEPUS would represent the first identified secreted member in this group of genes. We defined that this molecule forms the opioid-binding cell adhesion molecule (OBCAM) subfamily in the molecular phylogeny. Structurally, these molecules represent acidic proteins (pI 5.47-6.09). Six cysteins, as well as 5 Asn-linked potential glycosylation sites were evolutionary-conserved, suggesting that this OBCAM subfamily resembles immunoglobulin-like and highly glycosylated molecules. The presence of CEPUS would probably suggest to us that the spatial/local expression of the CEPU gene may provide a favorable route for migrating CEPU-positive population of neurons to generate a neuron-specific guidance in developing neurons in vivo.

Amino Acid Sequence↗

PubMed1999

GABA-mediated representation of temporal information in rat barrel cortex.

Temporal sequences of inputs to the rat whiskers are thought to be important to recognize the environment of the rat. In this study, we applied combined stimulations to neighboring whiskers D1 and D2, and the cortical activities evoked in the rat barrel cortex were measured using the intrinsic optical imaging technique. The timing of stimulation to neighboring whiskers affected the evoked cortical activities: the cortical activity evoked by in-phase stimulation to D1 and D2 was significantly stronger than that evoked by out-of-phase stimulation. In order to elucidate the mechanism underlying this phenomenon, the effect of blockade of cortical inhibitory circuits was examined. Iontophoretic application of bicuculline or saclofen (GABA-A or GABA-B antagonist) increased the evoked cortical activities and diminished the difference in activities obtained with in-phase and anti-phase stimulation. These results suggest that local inhibitory circuits play a critical role in coding temporal information of whisker stimulation.

Animals↗

PubMed1999

Acyl-CoA: cholesterol acyltransferase inhibitory activity of ginseng sapogenins, produced from the ginseng saponins.

Ginseng sapogenins were produced from ginseng saponins, isolated from Korean ginseng roots. Ginseng saponins very mildly inhibited acyl-CoA:cholesterol acyltransferase (ACAT) in vitro, however, the sapogenins showed strong inhibitory activity on microsomal ACAT. Therefore, the sapogenins will be one of key ingredients of ginseng affected a lowering of the serum total cholesterol level.

Animals↗

PubMed1999

Preparation of amino acid conjugates of betulinic acid with activity against human melanoma.

Betulinic acid has been coupled with a series of amino acids at C-28 carboxylic acid position and the toxicity of the derivatives has been evaluated against cultured human melanoma (MEL-2) and human epidermoid carcinoma of the mouth (KB) cell lines. A number of amino acid conjugates of betulinic acid showed improved water solubility as well as selective cytotoxicity. This investigation demonstrates that amino acid conjugates of betulinic acid can produce potentially important derivatives, which may be developed as antitumor agents.

Antineoplastic Agents↗

PubMed1999

New near-nerve needle nerve conduction technique: differentiating epicondylar from cubital tunnel ulnar neuropathy.

At the elbow, the ulnar nerve is compressed most commonly either in the epicondylar groove or at the cubital tunnel. While conventional electrodiagnosis may localize an ulnar neuropathy to the elbow, separating epicondylar syndrome (tardy ulnar nerve palsy) from cubital tunnel syndrome is more difficult. We describe a new method using a near-nerve needle technique for distinguishing these two types of ulnar neuropathy at the elbow. We placed three active needle electrodes across the elbow: the first was 4 cm above, and the second and third were 1.5 cm and 6 cm below the medial epicondyle, respectively. The latter two points were chosen because of the presence of the cubital tunnel in this segment. Sensory, motor, and mixed nerve conduction studies (NCS) were performed on these two segments (elbow segment and cubital tunnel segment) in 26 normal nerves and normal data were established. We also present 7 cases of epicondylar ulnar nerve palsy and 1 case of cubital tunnel syndrome in which we were able to confirm the diagnosis with the present method. In 3 cases of epicondylar ulnar nerve palsy, the present method accurately localized the lesion when other methods failed. We believe that this method will be helpful in distinguishing cubital tunnel syndrome from epicondylar ulnar nerve palsy, especially in early ulnar neuropathy in which only sensory fibers are involved.

Adult↗

PubMed1999

An immunohistochemical analysis of heat shock protein 70, p53, and estrogen receptor status in carcinoma of the uterine cervix.

OBJECTIVES: It has been shown that heat shock proteins (HSPs) protect cells from death caused by various noxious stimuli. Overexpression of HSP70 seems to be related to hormonal regulation of cell proliferation and/or down-regulation of sex steroid receptors. Wild-type p53 has been reported to repress HSP70 gene expression. It has been shown that mutant p53-HSP70 complex is highly expressed in cancer. However, the relationship between HSPs and steroid receptors or tumor suppressor gene products has not been well understood in uterine cervical carcinoma. This study was undertaken to examine the expression of HSP70, estrogen receptor (ER), and p53 in carcinoma of the uterine cervix. In addition, we analyzed HPV infection status and compared it to such immunohistochemical parameters. We also analyzed the relationship between these biological products and their clinicopathologic characteristics. METHODS: Paraffin-embedded tissue sections were obtained from 84 patients with carcinoma of the uterine cervix. Expression of HSP70, p53, and ER was evaluated by immunohistochemical staining using anti-HSP70 monoclonal antibody (SPA810), anti-p53 (BP53.12), and ER1D5 antibody, respectively. PCR HPV detection was done by dot hybridization method. RESULTS: Positive staining of HSP70 was detected in 73% of the cases. HSP70 positivity was significantly higher in stage I cervical cancer than in stages II-IV (P = 0.02). This was associated with neither tumor size, lymph node status, parametrial involvement status, nor tumor markers (TA-4). Furthermore, there was no significant correlation between HSP70 positivity and the expression of p53 or ER or HPV infection status. CONCLUSION: These data suggested that HSP70 positivity was frequent in uterine cervical cancer, especially in the early stages. However, this was not significantly correlated with clinicopathologic characteristics nor with the expression of p53 or ER nor with HPV infection in carcinoma of the uterine cervix.

Female↗

PubMed1999

Complete rectal prolapse: evolution of management and results.

UNLABELLED: Optional treatment for complete rectal prolapse remains controversial. PURPOSE: We reviewed our experience over a 19-year period to assess trends in choice of operation, recurrence rates, and functional results. METHODS: We identified 372 patients who underwent surgery for complete rectal prolapse between 1976 and 1994. Charts were reviewed and follow-up (median, 64: range, 12-231 months) was obtained by mailed questionnaire (149 patients; 40 percent) and telephone interview (35 patients; 9 percent). Functional results were obtained from 184 responders (49 percent). RESULTS: Median age of patients was 64 (11-100) years, and females outnumbered males by nine to one. One-hundred and eighty-eight patients (51 percent) were lost to follow-up; 183 patients (49 percent) underwent perineal rectosigmoidectomy, and 161 patients (43 percent) underwent abdominal rectopexy with bowel resection. The percentage of patients who underwent perineal rectosigmoidectomy increased from 22 percent in the first five years of the study to 79 percent in the most recent five years. Patients undergoing perineal rectosigmoidectomy were more likely to have associated medical problems as compared with patients undergoing abdominal rectopexy (61 vs. 30 percent, P = 0.00001). There was no significant difference in morbidity, with 14 percent for perineal rectosigmoidectomy vs. 20 percent for abdominal rectopexy. Abdominal procedures were associated with a longer length of stay as compared with perineal rectosigmoidectomy (8 vs. 5 days, P = 0.001). Perineal procedures, however, had a higher recurrence rate (16 vs. 5 percent, P = 0.002). Functional improvement was not significantly different, and most patients were satisfied with treatment and outcome. CONCLUSIONS: We conclude that abdominal rectopexy with bowel resection is associated with low recurrence rates. Perineal rectosigmoidectomy provides lower morbidity and shorter length of stay, but recurrence rates are much higher. Despite this, perineal rectosigmoidectomy has appeal as a lesser procedure for elderly patients or those patients in the high surgical risk category. For younger patients, the benefits of perineal rectosigmoidectomy being a lesser procedure must be weighed against a higher recurrence rate.Patient satisfaction]

Colon, Sigmoid↗

PubMed1999

Advanced method for determination of omeprazole in plasma by HPLC.

An advanced and sensitive high-performance liquid chromatographic (HPLC) method for determination of omeprazole in human plasma has been developed. After omeprazole was extracted from plasma with diethylether, the organic phase was transferred to another tube and trapped back with 0.1 N NaOH solution. The alkaline aqueous layer was injected into a reversed-phase C8 column. Lansoprazole was used as an internal standard. The mobile phase consisted of 30% of acetonitrile and 70% of 0.2 M KH2P04, pH 7.0. Recoveries of the analytes and internal standard were >75.48%. The coefficients of variation of intra- and inter-day assay were <5.78 and 4.59% for plasma samples. The detection limit in plasma was 2 ng/ml. The clinical applicability of this assay method was evaluated by determining plasma concentration-time courses of the respective analytes in 24 healthy volunteers after oral administration 40 mg of omeprazole. The present assay is considered to be simple, accurate, economical and suitable for the study of the kinetic disposition of omeprazole in the body.

Anti-Ulcer Agents↗

PubMed1999

The effects of exopolymers on cell morphology and culturability of Leuconostoc mesenteroides during starvation.

Biofilm formation by bacterial cells can be used to modify the subsurface permeability for the purpose of microbial enhanced oil recovery, bio-barrier formation, and in situ bioremediation. Once injected into the subsurface, the bacteria undergo starvation due to a decrease in nutrient supply and diffusion limitations in biofilms. To help understand the starvation response of bacteria in biofilms, the relationship between exopolymer formation and cell culturability was examined in a batch culture. The average cell diameter was observed to decrease from 0.8 micron to 0.35 micron 3 days after starvation began. Cell chain fragmentation was also observed during starvation. Cells that underwent starvation in the presence of insoluble exopolymers showed a slower rate of decrease in cell diameter and in cell chain length than cells without insoluble exopolymers. The rate of decrease in the average cell diameter and cell chain length were determined using a first order decay model. Cells starved in the presence of exopolymers showed greater culturability than cells starved without exopolymers. After 200 days starvation, 2.5 x 10(-3)% cells were culturable, but no increase in cell number was observed. During starvation, the exopolymer concentration remained constant, an indication that the exopolymer was not consumed by the starving bacteria as an alternative carbon or energy source.

Biofilms↗

PubMed1999

A new experimental model of obstructive hydrocephalus in the rat: the micro-balloon technique.

We used three types of specialized micro-balloons 0.7-1.35 mm in outer diameter instead of kaolin to develop a reproducible rat model of hydrocephalus with a low experimental mortality. The micro-balloon was inserted 6 mm deep into the cisterna magna via a burr hole immediately behind the lambda. The angle of introduction was 50 degrees. We also set up kaolin-induced hydrocephalic models in 25 rats as controls. The kaolin model revealed 52% mortality with an 80% induction rate of hydrocephalus, while the balloon model showed 9% mortality with a 60% induction rate. Balloon-induced hydrocephalus was maximal at 1 week and tended to decrease after 2-3 weeks. The pathological findings were not different between the two models. We concluded that the micro-balloon model for hydrocephalus is an easily reproducible model with low experimental mortality.

Animals↗