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Biomedical subjects

H T Kim

Publications and source records attributed to H T Kim.

114 records · Page 7Linked to original sources

Transverse myelitis in a patient with long-standing ankylosing spondylitis.

Ankylosing spondylitis is reported to involve not only the joints but other organs as well. Among these extra-articular involvements, uncommon complications associated with nervous system such as single root lesions, compression of the myelum and cauda equina syndrome have also been documented. Here we present a patient with long-standing ankylosing spondylitis who developed spastic paraparesis. Extensive study to find the cause of a spastic paraparesis failed and therefore led to the conclusion that this patient was suffering from transverse myelitis. Similar reports in the past have been attributed to an association with multiple sclerosis; however, we suggest that the findings support the diagnosis of a rare complication of ankylosing spondylitis with an unknown etiology.

Adult↗

In vitro generation of immune effector cells from tumor-associated lymphocytes of human gastric cancer.

Despite recent advances in cellular immunotherapy of cancer, the effectiveness of this type of treatment is limited only to some types of cancer. This study was performed to generate tumor-specific cytotoxic T lymphocytes (CTL) for the treatment of gastric cancer and to find the optimal culture conditions for this CTL, because most immune effector cells used in the previous trials were non-specific killers. Lymphocytes were isolated from tumors, tumor-draining lymph nodes, malignant ascites and peripheral blood of 29 patients with gastric cancer. Lymphocytes from each source were then cultured for three weeks under one or more of the following conditions: 1) 50 U/ml of rIL-2; 2) 50 U/ml of rIL-2 + irradiated (6,000 rad) fresh autologous tumor cells (in vitro sensitization - IVS); 3) 1,000 U/ml of rIL-2; 4) 1,000 U/ml of rIL-2 + IVS. The study found that 1,000 U/ml of rIL-2 generated higher cytotoxicity against allogeneic tumor targets than 50 U/ml of rIL-2 (p < 0.05). However, neither the concentration of rIL-2, lymphocyte source, nor IVS produced any significant differences in cytotoxicity against fresh autologous tumor cell targets. The data suggested that immune effector cells for gastric cancer could be generated efficiently, but it was difficult to produce CTL specific for autologous tumor cells of gastric cancer using a low concentration of rIL-2 and/or in vitro sensitization with autologous irradiated tumor cells.

Cells, Cultured↗

In vitro antitumor activity of a new platinum complex, cis-malonato [(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum (II) (SKI 2053R), against human lung and stomach cancer cell lines.

The in vitro antitumor activity of a new platinum complex, cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolan e] platinum(II) (SKI 2053R, NSC D644591), cisplatin (CDDP) and carboplatin (CBDCA) was determined against two human lung cancer (PC-9 and PC-14) and two human stomach cancer (MKN-45 and KATO III) cell lines by human tumor clonogenic assay. The activity of SKI 2053R was compared with those of CDDP and CBDCA in terms of relative antitumor activity (RAA, peak plasma concentration/IC50). Mean IC50 values (microgram/ml) of SKI 2053R, CDDP and CBDCA were 6.4 +/- 0.8, 1.8 +/- 0.7 and 20.6 +/- 12.2, respectively. The RAAs of SKI 2053R, CDDP and CBDCA were 1.6 +/- 0.4, 2.0 +/- 0.8 and 1.2 +/- 0.6, respectively. The differences in these values were not statistically significant. The results, demonstrating that antitumor activity of SKI 2053R is similar to those of CDDP and CBDCA, suggest that SKI 2053R is an interesting candidate for further development as a new anticancer drug.

Adenocarcinoma↗

In vitro cytotoxicity, pharmacokinetics and ex vivo pharmacodynamics of a new platinum compound, cis-malonato [(4R,5R-4,5-bis(aminomethyl)-1,3-dioxolane-2-spiro-1'-cyclopentane] platinum (II).

The in vitro cytotoxicity of a new platinum complex, cis-malonato [(4R, 5R)-4,5-bis(aminomethyl)-1,3-dioxolane 2- spiro 1' cyclo-pentane]platinum(II) (SKI 2054R) and cisplatin (CDDP) was evaluated against two human stomach adenocarcinoma cell lines (MKN-45 and KATO III) and a human lung adenocarcinoma cell line (PC-14). The in vitro 50% inhibitory concentration (IC50) values of SKI 2054R and CDDP against MKN-45, KATO III, and PC-14 were 1.21 and 0.51, 2.11 and 0.83, and 2.90 and 0.77 micrograms/ml, respectively. The pharma-cokinetic and ex vivo pharmacodynamic studies on SKI 2054R and CDDP were performed in beagle dogs. Equitoxic doses of SKI 2054R and CDDP (7.0 and 3.0 mg/kg, respectively) were administered i.v. bolus to beagle dose in a randomized crossover study. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for the two drugs declined in a biexponential fashion. The mean area under the concentration-tine curve (AUC(0)--> infinity) determined for ultrafiltrable platinum derived from SKI 2054R, as an active component was 6.61 +/- 2.34 micrograms . h/ml (mean +/- S.D.), with an initial half-life of 0.26 +/- 0.14 h, a terminal half-life of 1.57 +/- 0.71 hour, a total clearance of 17.65 +/- 4.99 ml/min/kg, and a steady-state volume of distribution of 1.46 +/- 0.11 l/kg. The ex vivo antitumor activity of SKI 2054R was assessed using the ultrafiltrable plasma against MKN-45, KATO III, and PC-14 by tetrazolium-dye (MTT) assay and was compared with that of CDDP using the antitumor index (ATI) determined from the ex vivo pharmacodynamic results of inhibition rates (%) versus time curves. The mean ATI value recorded for SKI 2054R was higher than that noted for CDDP; however, statistical difference was not observed between SKI 2054R and CDDP, suggesting that the antitumor activity of SKI 2054R is comparable to that of CDDP. These results suggest that SKI 2054R is a new platinum complex which is worth being evaluated further.

Adenocarcinoma↗

Pharmacokinetics of a new platinum compound, cis-(glycolato-O,O) [(4R,5R)-4,5-bis(aminomethyl)-1,3-dioxolane-2-spiro-1'-cyclohexane]plat inum (II) in dogs.

A pharmacokinetic study on cis-(glycolato-O,O)/ (4R,5R)-4,5-bis(aminomethyl)-1,3-dioxolane-2-spiro-1'- cyclohexane]platinum(II) (SKI 2032R) was performed in dogs. A single dose of 2.0 mg/kg of SKI 2032R was administered i.v. bolus to three beagle dogs. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for SKI 2032R declined in a biexponential fashion. The mean area under the concentration-time curve (AUC0 --> infinity) determined for ultrafiltrable platinum derived from SKI 2032R, as an active component, was 2.36 +/- 0.23 micrograms. h/ml (mean +/- S.D.), with an initial half-life of 0.23 +/- 0.20 hour, a terminal half-life of 1.32 +/- 0.49 hour, a total clearance of 14.17 +/- 1.50 ml/min/kg, and a steady-state volume of distribution of 1.21 +/- 0.24 l/kg.

Animals↗

Pharmacokinetics of platinum following the administration of cis-(glycolato-O,O')[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1, 3-dioxolane]platinum(II) in dogs.

The pharmacokinetic study on cis-(glycolato-O,O') [(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]-platinum(II) (SKI 2034R, NSC D642489) was performed in beagle dogs. A single dose of 2.0 mg/kg of SKI 2034R was given by i.v. bolus to three beagle dogs. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for SKI 2034R declined in a biexponential fashion. The mean area under the concentration-time curve (AUC0-->infinity) determined for ultrafiltrable platinum derived from SKI 2034R, as an active component, was 2.76 +/- 0.13 micrograms.h/ml (mean +/- S.D.), with an initial half-life of 0.15 +/- 0.09 hour, a terminal half-life of 0.96 +/- 0.12 hour, a total clearance of 12.07 +/- 0.67 ml/min/kg, and a steady-state volume of distribution of 0.82 +/- 0.06 1/kg.

Animals↗