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Biomedical subjects

J S Kim

Publications and source records attributed to J S Kim.

At least 37 records · Page 2Linked to original sources

Emergence of Escherichia coli isolates producing conjugative plasmid-mediated DHA-1 beta-lactamase in a Korean university hospital.

Seven isolates of cefoxitin-resistant Escherichia coli with an inducible phenotype were detected between November 2002 and July 2003 in a Korean hospital. Conjugations were tested by the filter mating method using azide-resistant E. coli J53 as the recipient. All isolates and their transconjugants were tested for broth microdilution minimum inhibitory concentrations, isoelectric focusing (IEF), polymerase chain reaction (PCR) for SHV, TEM, CTX-M and DHA-derived beta-lactamases, and DNA sequencing. XbaI-digested genomic DNA bands of the seven isolates were separated by pulsed-field gel electrophoresis (PFGE). IEF, PCR and sequence analysis revealed that all isolates possessed a blaTEM-1-like and a blaDHA-1 gene. Two isolates also carried the blaCTX-M-14 gene. Transfer of the resistance by conjugation experiments of all seven isolates was successful, suggesting that the blaDHA-1-containing plasmids in the E. coli isolates were self-transmissible. The isolates were recovered from patients in wards or an intensive care unit, all of which had been exposed to beta-lactams before isolation of the DHA-1 producers. Five patterns among the seven isolates were demonstrated by PFGE; sporadic infections with E. coli possessing an inducible beta-lactam resistance phenotype were found. DHA-1 encoded by conjugative plasmids conferred the resistance phenotype. The spread of the DHA-1 producers was due to both clonal spread and horizontal transfer of the resistance gene.

Adult↗

Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a targeted poxvirus expressing GM-CSF.

Targeted oncolytic viruses and immunostimulatory therapeutics are being developed as novel cancer treatment platforms. These approaches can be combined through the expression of immunostimulatory cytokines from targeted viruses, including adenoviruses and herpesviruses. Although intratumoral injection of such viruses has been associated with tumor growth inhibition, eradication of distant metastases was not reported. The major limitations for this approach to date have been (1) inefficient intravenous virus delivery to tumors and (2) the lack of predictive, immunocompetent preclinical models. To overcome these hurdles, we developed JX-594, a targeted, thymidine kinase(-) vaccinia virus expressing human GM-CSF (hGM-CSF), for intravenous (i.v.) delivery. We evaluated two immunocompetent liver tumor models: a rabbit model with reproducible, time-dependent metastases to the lungs and a carcinogen-induced rat liver cancer model. Intravenous JX-594 was well tolerated and had highly significant efficacy, including complete responses, against intrahepatic primary tumors in both models. In addition, whereas lung metastases developed in all control rabbits, none of the i.v. JX-594-treated rabbits developed detectable metastases. Tumor-specific virus replication and gene expression, systemically detectable levels of hGM-CSF, and tumor-infiltrating CTLs were also demonstrated. JX-594 holds promise as an i.v.-delivered, targeted virotherapeutic. These two tumor models hold promise for the optimization of this approach.

Animals↗

Oxidative stress during peritoneal dialysis: implications in functional and structural changes in the membrane.

Progressive peritoneal fibrosis, membrane hyperpermeability, and ultrafiltration failure have been observed in patients on long-term peritoneal dialysis (PD). The present study tested the hypothesis that reactive oxygen species (ROS) generated by conventional PD solution (PDS) mediate functional and structural alterations of peritoneal membrane in vivo. Sprague-Dawley rats were randomized to control, PDS, PDS with an antioxidant, and PDS with an angiotensin II (Ang II) receptor blocker. Commercial PDS containing 3.86% glucose (20-30 ml) with or without N-acetylcystein (NAC) 10 mM or losartan 5 mg/kg was administered intraperitoneally twice a day for 12 weeks. Control rats received sham injection. Rats treated with PDS had significantly lower drain volume and D(4)/D(0) glucose, but higher D(4)/P(4) creatinine and increased membrane thickness and endothelial NOS (eNOS) expression compared to control rats. Omental transforming growth factor (TGF)-beta1, vascular endothelial growth factor (VEGF), collagen I, and heat-shock protein (hsp) 47 expression and lipid peroxide levels and dialysate VEGF and Ang II concentrations were significantly increased in rats treated with PDS compared to control. All of these changes were prevented by both NAC and losartan. In conclusion, the present study demonstrates that ROS generated by conventional PDS are, in large part, responsible for peritoneal fibrosis and membrane hyperpermeability. We suggest that antioxidants or Ang II receptor blockers may allow better preservation of the structural and functional integrity of the peritoneal membrane during long-term PD.

Angiotensin II Type 1 Receptor Blockers↗

Controlled delivery of a hydrophilic drug from a biodegradable microsphere system by supercritical anti-solvent precipitation technique.

The purpose of this study was to prepare microspheres loaded with hydrophilic drug, bupivacaine HCl using poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). Microspheres were prepared with varying the PLGA/PLLA ratio with two different levels of bupivacaine HCl (5 and 10%) using a supercritical anti-solvent (SAS) technique. Microspheres ranging from 4-10 microm in geometric mean diameter could be prepared, with high loading efficiency. Powder X-ray diffraction (PXRD) revealed that bupivacaine HCl retained its crystalline state within the polymer and was present as a dispersion within the polymer phase after SAS processing. The release of bupivacaine HCl from biodegradable polymer microspheres was rapid up to 4 h, thereafter bupivacaine HCl was continuously and slowly released for at least 7 days according to the PLGA/PLLA ratio and the molecular weight of PLLA.

Absorbable Implants↗

Analysis of cell growth in three-dimensional scaffolds.

The in vitro growth of pre-osteoblasts in multi-layer, three-dimensional scaffolds was determined from experimental measurements and was compared to a mathematical model. Immediately following cell seeding, the initial cell density was uniform throughout the scaffold. After 10 days, the cell density increased from 2.1 x 10(5) cells/cm(3) to 1.3 x 10(7) cells/cm(3) at the fluid-scaffold interface. The increase in cell density was largely confined to the outermost 200 microm from the fluid-scaffold interface. The cell density profile was in good agreement with a mathematical model that simulated the cell growth based on the local oxygen tension. The improved understanding derived from this mathematical model may be useful in the design of three-dimensional scaffolds that can support more uniform growth of cells.

3T3 Cells↗

Cerebellar hypermetabolism in paraneoplastic cerebellar degeneration.

A 51 year old man with paraneoplastic cerebellar degeneration from gastric adenocarcinoma showed cerebellar hypermetabolism and increased perfusion on brain FDG-PET scan and SPECT during the acute stage of his illness. The patient underwent subtotal gastrectomy. The intensity of the hypermetabolism had decreased markedly on follow-up FDG-PET 3 months later following two cycles of chemotherapy. We suggest that the cerebellar hypermetabolism may have been due to an acute inflammatory process associated with an immunological reaction.

Cerebellar Neoplasms↗

Eugenol inhibits sodium currents in dental afferent neurons.

Although eugenol is widely used in dentistry, little is known about the molecular mechanisms responsible for its anesthetic properties. In addition to calcium channels, recently demonstrated by our group, there could be another molecular target for eugenol. Using a whole-cell patch-clamp technique, we investigated the effect of eugenol on voltage-gated sodium channel currents (I(Na)) in rat dental primary afferent neurons identified by retrograde labeling with a fluorescent dye in maxillary molars. Eugenol inhibited action potentials and I(Na) in both capsaicin-sensitive and capsaicin-insensitive neurons. The pre-treatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid 1 (TRPV1), failed to block the inhibitory effect of eugenol on I(Na), suggesting no involvement of TRPV1. Two types of I(Na), tetrodotoxin (TTX)-resistant and TTX-sensitive I(Na), were inhibited by eugenol. Our results demonstrated that eugenol inhibits I(Na) in a TRPV1-independent manner. We suggest that I(Na) inhibition by eugenol contributes to its analgesic effect.

Action Potentials↗

Comparative pharmacokinetic and pharmacodynamic characteristics of amlodipine besylate and amlodipine nicotinate in healthy subjects.

BACKGROUND AND AIM: Amlodipine, a dihydropyridine calcium antagonist, is prescribed for the management of angina and hypertension, and is sold as amlodipine besylate. However, a new salt formulation, amlodipine nicotinate, has recently been developed. Here, we evaluated the comparative pharmacokinetic and pharmacodynamic characteristics of the nicotinate and besylate forms of amlodipine. SUBJECTS AND METHODS: A randomized, 2-way crossover study was conducted in 18 healthy male volunteers to compare the pharmacokinetics and pharmacodynamics of these two forms, i.e. amlodipine nicotinate (test) and amlodipine besylate (reference), after administration of a single dose of 5 mg of each drug and a washout period between doses of 4 weeks. Blood samples for the pharmacokinetic analysis of amlodipine were obtained over the 144-hour period after administration. Systolic and diastolic blood pressures and pulse rates were recorded immediately prior to each blood sampling. RESULTS: All participants completed both treatment periods, and no serious adverse events occurred during the study period. After administering a single dose of each formulation, mean AUC0-infinity and Cmax values were 190.91+/-60.49 ng x h/ml and 3.87+/-1.04 ng/ml for the test formulation and 203.15+/-52.05 ng x h/ml and 4.01+/-0.60 ng/ml for the reference formulation, respectively. The 90% confidence intervals of test/reference mean ratios for AUC0- infinity and Cmax fell within the predetermined equivalence range of 80 - 125%. Pharmacodynamic profiles including systolic and diastolic blood pressures and pulse rates exhibited no significant differences between the two formulations. CONCLUSION: The two amlodipine formulations showed similar pharmacokinetic and pharmacodynamic characteristics and the new amlodipine formulation, amlodipine nicotinate, was found to be equivalent for pharmacokinetics to the currently available amlodipine besylate with respect to the rate and extent of amlodipine absorption.

Administration, Oral↗

The association between CD99 and LMP-1 expression in nasopharyngeal carcinoma.

AIM: To characterize the roles of LMP-1 and CD99 in nasopharyngeal carcinogenesis, we undertook this pilot study of LMP-1 and CD99 expressions in nasopharyngeal cancer (NPC). MATERIALS AND METHOD: 40 NPC tissue samples were grouped according to the WHO classification. Immunohistochemical studies were performed using monoclonal antibodies against EBV latent membrane protein 1 (LMP-1) and CD99 protein. In addition, CD99 expression was evaluated in 10 samples of non-neoplastic nasopharyngeal epithelium. RESULTS: LMP-1 was detected in 12 of the 40 (30.0%) cases and its expression was found to be confined to epithelial tumor cells. WHO type I NPC samples were completely negative for LMP-1, whereas WHO type III NPC samples showed highest expression. Interestingly, CD99 was expressed in all of the non-neoplastic nasopharyngeal epithelium samples along the cytoplasmic border. CD99 expression was noted in NPC tumor cells (5 of the 40 cases, 12.5%) and in surrounding lymphoid stroma (23 of the 40 cases, 57.5%), but was not expressed in WHO type I NPC. In the 12 LMP-1 positive cases, 9 cases (75.0%) were CD99 negative, and 3 cases (25.5%) were CD99 positive. There was a statistical significance between LMP-1 and CD99 expression in lymphoid stroma. CONCLUSION: Our results suggest that the LMP-1 induced down-regulation of the CD99 pathway is important in nasopharyngeal carcinogenesis, and that the expression of CD99 in lymphoid stroma may regulate immune response to NPC.

12E7 Antigen↗

Rotational vertebral artery syndrome: oculographic analysis of nystagmus.

In four patients with rotational vertebral artery syndrome (RVAS), the initial nystagmus was mostly downbeat, with the horizontal and torsional components beating toward the compressed vertebral artery side (n = 3) or directed away (n = 1). Three patients showed spontaneous reversal of the nystagmus and two exhibited no or markedly diminished responses on immediate retrial of head rotation (habituation). The patterns of nystagmus suggest that RVAS may result from differing mechanisms.

Aged↗

Characterization of a pollen-preferential gene, BAN102, from Chinese cabbage.

We isolated and characterized a pollen-preferential gene, BAN102, from Chinese cabbage and analyzed the activity of its promoter. There were three or four copies of the BAN102 gene in the Chinese cabbage genome that specifically expressed in pollen and pollen tube. There were 2137 bp of BAN102 genomic clone comprising 186 bp of protein coding region, and 1178 bp of 5' and 773 bp of 3' non-coding regions. TATA box were located at 1071 nt of the promoter region while the polyadenylation signal and polyadenylation site were at 1470 and 1486 nt of the 3' non-coding region. BLAST search of BAN102 sequence showed that coding region of BAN102 gene was the greatest percent similarity with arabinogalactan protein (AGP23) gene from Arabidopsis thaliana. Promoter analysis using GUS gene as a reporter showed that the pollen-specificity of BAN102 resided within the -112 to -44 bp of proximal promoter from the transient expression in tobacco and Chinese cabbage plants.

Base Sequence↗

Cardiac 123I-MIBG scintigraphy in patients with drug induced parkinsonism.

Cardiac sympathetic dysfunction was investigated using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 20 patients with drug induced parkinsonism (DIP). The mean heart to mediastinum ratio was significantly greater in patients with DIP than in those with Parkinson's disease (mean (SD): 2.07 (0.39) v 1.28 (0.15), p<0.001). MIBG uptake was not different between the DIP patients and controls. Two DIP patients whose MIBG uptake was significantly reduced showed persistent parkinsonism and responded dramatically to levodopa.

Adult↗

Docetaxel (Taxotere), cisplatin, UFT, and leucovorin combination chemotherapy in advanced gastric cancer.

We conducted this study to ascertain the efficacy and toxicity of docetaxel and cisplatin combined with oral UFT and leucovorin as a first-line treatment for patients with advanced gastric cancer. In all, 52 patients received courses of docetaxel 60 mg m(-2) intravenously (i.v.) for 1 h and then cisplatin 75 mg m(-2) i.v. for 2 h on day 1. Oral UFT at 400-600 mg day(-1), as determined by body surface area, and leucovorin at 75 mg day(-1) were administered for 21 consecutive days from day 1, and this was followed by a 7-day drug-free interval. A total of 225 courses were administered, and the median number of courses per patient was four. Four complete responses (7.7%) and 22 partial responses (42.3%) were achieved, giving an overall response rate of 50% (95% Confidence Interval: 36.4-63.6%). The major toxicity was neutropenia, which reached grade 3/4 in 36 patients (69.3%). Grade 3/4 nausea and vomiting was observed in 12 patients (23.1%). Median time to progression was 22 weeks (4 to 156+ weeks), median survival duration was 48 weeks (4 to 156+ weeks), and median response duration was 24 weeks (6-152 weeks). We conclude that docetaxel, cisplatin, oral UFT, and leucovorin combination chemotherapy is effective and tolerable for the treatment of advanced gastric cancer.

Adenocarcinoma↗

Immunochemical and biological analysis of allergenicity with excretory-secretory products of anisakis simplex third stage larva.

BACKGROUND: Anisakis simplex third stage larvae (L3) are parasites that frequently give rise to allergic responses. The larvae molt into fourth stage larvae (L4), and at each stage they produce L3-excretory-secretory products (L3-ESP) and L4-ESP, respectively, which are different in their main protein constituents. Although the allergenicity of L4-ESP has been investigated by several research groups, research on the allergenicity of L3-ESP has not been carried out by any researcher. In this investigation, the allergenicity and antigenicity of L3-ESP were investigated in comparison with L4-ESP, using rat sera. METHODS: Rat sera were produced by L3 oral infection two times with a 9-week interval. Larvae ESP prepared by culture were concentrated and fractioned using lyophilizer and a centrifugal filter device, respectively. Immunochemical analysis was performed using both indirect ELISA and immunoblot. Biological allergenicity was analyzed by RBL-2H3 exocytosis. RESULTS: With the indirect ELISA, the optical density (OD) value of the nonfractioned (NF)-L3ESP was only one third of that of the NF-L4ESP in both specific IgM and IgG. On measuring specific IgE, the OD of NF-L3ESP was less than one tenth of that of NF-L4ESP. In addition, neither antigen nor allergen was shown in NF-L3ESP, but it was shown in NF-L4ESP with immunoblot. However, the biological allergenicity of NF-L3ESP was comparable to that of NF-L4ESP. To demonstrate the presence of any allergen, L3-ESP was fractioned and found to carry twelve visualized allergen bands from 10 to 186 kDa by immunoblot. CONCLUSIONS: These results indicate that L3-ESP may include the important allergens necessary to induce the allergy by L3 oral infection, as compared to L4-ESP.

Allergens↗

Single-stage operation for bilateral middle cerebral artery aneurysms.

BACKGROUND: Subarachnoid haemorrhage with bilateral middle cerebral artery aneurysms is occasionally encountered in neurosurgical practice. We report upon our experiences of the single-stage operation for bilateral middle cerebral artery aneurysms (BMCA) through a bilateral subfrontal approach. METHODS: During the past two and half years, we have experienced three cases of BMCAA, who were treated by this method. The whole procedure was conducted using a single-stage head positioning and draping. Slight table tilting was enough to allow the proper clipping of each aneurysm. FINDINGS: During the past 2.5 years, 255 cases of intracranial aneurysm have been treated in our hospital. Among these, the incidence of BMCAA was 1.18% (3/255). The mean duration of operation for the three cases involved was 5.8 hours, and showed a progressive decrease with experience. All patients recovered well, and were discharged as in other uneventful aneurysm cases. The total operation time was longer, and was a little more laborious than normal single aneurysm surgery. CONCLUSION: This method has substantial advantages over "classical" skull base approaches to MCA aneurysms. As extensive frontal lobe manipulation and external facial incisions are avoided with subfrontal approaches, intensive care unit and overall hospital stay are reduced, related complications are minimized, and postoperative cosmetic appearance is enhanced.

Adult↗

Primary colon lymphoma in Korea: a KASID (Korean Association for the Study of Intestinal Diseases) Study.

Although almost all primary colorectal lymphomas are of B-cell lineage in Western countries, primary colorectal T-cell lymphomas are not uncommon in the East. The aim of this study was to review the clinical characteristics and treatment outcomes of primary colorectal lymphomas, with special emphasis on the differences between T-cell and B-cell lymphomas. Ninety-five cases of primary colorectal lymphomas that satisfied Dawson's criteria were identified from the clinical databases of 13 university hospitals in Korea. The mean age at the time of presentation was 51.1 years and the male:female ratio was 64:31. The clinical information, including endoscopic and histological characteristics, was retrospectively analyzed. Of the primary colorectal lymphomas, 78 cases (82.1%) were of B-lineage and 17 cases (17.9%) were of T-cell lineage. Patients with T-cell lymphomas presented at a younger age than patients with B-cell lymphomas (42.8 vs 52.9 years, respectively; P = 0.016). The most common presenting symptom was abdominal pain (87.1%) for B-cell lymphomas, whereas hematochezia or night fever was more common for T-cell lymphomas (52.9% and 35.3%, respectively). The most common endoscopic type was fungating mass (54.0%) for B-cell lymphomas and ulcerative/ulcero-infiltrative lesions (80.0%) for T-cell lymphomas. Intussusception was more common in B-cell lymphomas than in T-cell lymphomas (30.8% vs 5.9%, respectively; P = 0.035), but perforation was more common in T-cell lymphomas than in B-cell lymphomas (23.5% vs 3.8%, respectively; P = 0.005). The prognosis was significantly worse for T-cell lymphomas than for B-cell lymphomas (P = 0.002). Primary colorectal T-cell lymphomas are characterized by multifocal ulcerative lesions in relatively young patients, a high rate of hematochezia, fever, or perforation, and a poor prognosis even for cases of localized disease.

Adolescent↗