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Biomedical subjects

D J Kim

Publications and source records attributed to D J Kim.

At least 199 records · Page 11Linked to original sources
PubMed1992

Effects of buthionine sulfoximine treatment on cellular glutathione levels and cytotoxicities of cisplatin, carboplatin and radiation in human stomach and ovarian cancer cell lines.

Chemotherapy failure remains a significant medical problem in the treatment of neoplastic disease and is thought to be due to many different factors including membrane transport, p-glycoprotein in multidrug resistance, glutathione and its related enzymes, topoisomerase II and DNA repair. Glutathione is a major constituent of non-protein thiol and participates in detoxification of chemotherapy and radiation. Thus, glutathione concentration is correlated with sensitivity to alkylating agents and radiation, and increased in resistant cell lines. Buthionine sulfoximine (BSO) is an inhibitor of glutathione biosynthesis and may increase cytotoxicities of alkylating agents, including melphalan and cisplatin, and radiation in sensitive and resistant cell lines. We studied effects on cellular glutathione levels and cytotoxicities of cisplatin, carboplatin and radiation by BSO treatment in human stomach cancer cell line (SNU-1) and ovarian cancer cell line (OVCAR-3). The results were as follow: 1) After BSO treatment of 1 mM and 2 mM for 2 days, the intracellular thiol concentration was depleted to 75.7% and 76.2% in SNU-1, and 74.1% and 63.0% in OVCAR-3, respectively. 2) The intracellular thiol concentration in SNU-1 was depleted to 33.4% after BSO 2 mM for only 2 hours incubation and 71.5% after small amount of BSO (0.02 mM) for 2 days. 3) The recovery of intracellular thiol concentration required more than 3 days after BSO removal. 4) BSO inhibited partially the growth of SNU-1 and OVCAR-3. 5) The cytotoxicities of cisplatin and carboplatin were markedly enhanced both in SNU-1 and OVCAR-3 by BSO treatment. 6) The cytotoxicities of radiation was increased in OVCAR-3 and SNU-1 by BSO treatment. Therefore, it is concluded that BSO can deplete effectively the intracellular thiol concentration and enhance the cytotoxicities of cisplatin, carboplatin and radiation.

Antimetabolites, Antineoplastic↗
PubMed1992

Allogeneic bone marrow transplantation for the patients with hemopoietic stem cell disorders: CUMC experience.

Bone marrow transplantation from an HLA-identical sibling is increasingly used as a curative therapy for patients with hemopoietic stem cell disorders including acute leukemia, chronic myelogenous leukemia and severe aplastic anemia. Between March 1983 and March 1991, we performed 86 cases of allogeneic bone marrow transplantation (BMT) for the patients with hemopoietic stem cell disorders: 25 acute myelogenous leukemia (AML); 15 acute lymphoblastic leukemia (ALL); 20 chronic myelogenous leukemia (CML); and 26 severe aplastic anemia (SAA). Ten out of 25 AML are in disease free survival (DFS). The causes of death were recurrence of leukemia (12), acute GVHD (3), sepsis (1) and veno-occlusive disease (1). Nine of 15 ALL are in unmaintained remission. Thirteen out of 20 CML are in DFS. Among 26 SAA, 21 are enjoying DFS, but 1 died of engraftment failure, 3 of graft rejection followed by cytomegalovirus (1) and aspergillus pneumonia (1). Comparing the survival between standard [less than or equal to CR1: 9/14 (64%)] and high risk [greater than or equal to CR1: 1/11 (9%)] AML, our data suggest that preparative regimen for high risk AML was not potent enough to eradicate the minimal residual disease in advanced AML. Although our cases are limited and the follow-up period is short, our result of ALL [overall: CCR (60%), standard risk (adult less than or equal to CR1, children less than or equal to CR2; 8/11 (73%) and high risk; 1/4 (25%)] and CML [overall: 65%, CP; 9/10 (90%), AP; 4/6 (67%), BP; 0/4 (0%)] are optimistic. It is of our interest that the incidence of death related with IP (1/33: 3%) and with AGVHD 94/33: 12%) were much less than that of other's observation but the explanation for this still remains to be clear.

Acute Disease↗
PubMed1991

Analysis of the higher-order echoes in SSFP.

In the steady-state free precession (SSFP) with an applied linear gradient, the transverse magnetizations are periodically distributed. Fourier analysis of this periodic distribution leads to the understanding of many interesting phenomena in SSFP. It is found that there are many other higher-order echoes in SSFP in addition to the previously known echoes. By deriving general description of the transverse magnetization of SSFP and by expanding the echo time independent term with Fourier series, the higher-order echoes including the two previously known FISP and CE-FAST are understood and explained. These higher-order echoes are studied in detail by both computer simulation and experiments and their results are reported.

Computer Simulation↗
PubMed1991

Cell cycle-dependent entry of Toxoplasma gondii into synchronized HL-60 cells.

The degree of attraction of Toxoplasma gondii to vertebrate cells varies with cell type and cell phase. Human promyelocytic leukemia cells, HL-60, were synchronized by double thymidine block method and co-cultured with Toxoplasma for 1 hr at each cell stage to investigate the cell cycle specific susceptibility of parasites to host cells. For 30 hr the average number of Toxoplasma that invaded was a little changed except at 3 hr from G1/S phase boundary which concurred with the peak point of DNA synthesis. At 3 hr which is a relatively short interval compared to whole S phase, modification of cells by parasitic invasion was most remarkable. The number of Toxoplasma that penetrated was increased to more than six times. The shape of the cells became sludgy and almost indiscernible by strong accessibility of parasites only for an hour of mid-S phase. The same fluctuation was also observed at the second peak of S phase but weakly. This suggests that there be surface molecules concerning with the attachment of Toxoplasma to the host cells, which is expressed at special point of S phase. Further studies on the specific protein or similar molecules related could be carried out using synchronized HL-60 cells.

Animals↗
PubMed1991

Anterior interbody fusion for spondylolisthesis.

We evaluated the clinical and radiologic results and the immobilizing effect of the Knight-Kim brace for bony union in 75 consecutive cases of spondylolisthesis treated by anterior interbody fusion. The fifth lumbar vertebra was the most common site involved (55%). The patients were followed for a minimum of 2 1/2 years (range: 2 1/2 to 14; average: 4.5). All cases were approached retroperitoneally, and autogenous bone graft was obtained from the iliac crest. The donor site was reconstructed by polymethylmethacrylate bone cement. Among the 75 cases of grade I, II, and III slippage according to Meyerding's grading system, 58 cases (77%) showed complete bony union after 1 year follow up. Excellent and good clinical results were obtained in 65 cases (87%) at 1 year postoperatively. The state of bony union did not always correlate with the clinical symptoms. We conclude that the simple Knight-Kim back brace was valuable for postoperative immobilization.

Adult↗
PubMed1990

Purification and properties of ampicillin acylase from Pseudomonas melanogenum.

Ampicillin acylase, which is known to have a novel substrate spectrum, was purified to homogeneity from Pseudomonas melanogenum by the crude extract preparation and chromatography with S-Sepharose, hydroxyapatite, CM-cellulose C-52, and CM-Sepharose. The molecular weight of the native enzyme was calculated to be 146,000 by Protein PAK-300 sw HPLC chromatography. SDS-polyacrylamide gel electrophoresis revealed that the enzyme consisted of two identical subunits with a molecular weight of 72,000. The enzyme was a glycoprotein containing 13% of total carbohydrate, and its isoelectric point was 7.2. The enzyme catalyzed both synthesis and hydrolysis of ampicillin and hydrolysis of the ester bond of phenylglycinemethylester hydrochloride substrate. The substrate specificity showed that the enzyme required a free amino group on the alpha-carbon of the acyl group. Chemical modification by diethylpyrocarbonate or N-bromosuccinimide resulted in time-dependent inactivation of the enzyme, and other results suggest the participation of essential histidine residue(s) in the catalytic activity of ampicillin acylase. Substrates of the enzyme, 6-aminopenicillanic acid and ampicillin, exhibited protective effects against N-bromosuccinimide inactivation, suggesting that the modification occurred near or at the active site.

Amidohydrolases↗
PubMed1990

Evidence for involvement of 2 histidine residues in the reaction of ampicillin acylase.

The chemical modification of purified ampicillin acylase by N-bromosuccinimide and diethylpyrocarbonate resulted in time-dependent inactivation of the enzyme. Both substrates, ampicillin and 6-aminopenicillanic acid, protected the enzyme against inactivation, suggesting that the modification occurred near or at the active site. Amino acid analyses and other data indicated that two histidyl residues per subunit molecule were essential for catalytic activity.

Amidohydrolases↗
PubMed1990

Extraction of cardiac and respiratory motion cycles by use of projection data and its applications to NMR imaging.

A technique of extracting cardiac and respiratory motion cycles by use of projection data is proposed and studied. These extracted cardiac and respiratory motion cycles are applied to the cine imaging of heart and motion artifact reduction in abdominal imaging instead of the conventional ECG gating devices. The basic concepts and their applications are discussed. Experimental results on human volunteers obtained with the KAIS 2.0-T whole-body NMR imaging system together with the pulse sequences used for the experiments are presented.

Heart↗
PubMed1990

Cytotoxic activity of lysophosphatidylcholine analogues on human lymphoma Raji cells.

The cytotoxic activity of 21 lysophosphocholine analogues was tested on human lymphoma Raji cells. Structure-activity investigations revealed a more than 50-fold difference in the cytotoxicity between the different compounds. Whereas acyllysophosphocholines showed only borderline effects, the most pronounced toxic activity was observed with compounds which have an etherbond in the sn-1 position and a hydrogen, a methoxy or a methoxymethylgroup in position sn-2. Elongation of the phosphorous-nitrogen distance in the choline group markedly reduced the cytotoxicity of the compounds. From the results obtained it was concluded that a long chain fatty alcohol adjacent to a phosphocholine headgroup represents the minimal requirement for antineoplastic activity. Thus, a new group of antineoplastic compounds, the alkylphosphocholines, was developed in our laboratory, with in vitro cytotoxic activities just as effective as the most toxic alkyllysophosphocholines.

Antineoplastic Agents↗
PubMed1990

The effect of cyclic AMP on the growth of Toxoplasma gondii in vitro.

To assess the role of cAMP on the growth and proliferation of Toxoplasma in HL-60 cells we tested the effect of exogenous cAMP and cAMP analogues to the co-culture system of Toxoplasma and HL-60 cells. cAMP, dbcAMP, and br-cAMP stimulated the growth of Toxoplasma at a specific concentration, i.e., 10(0) mM, 10(0) mM, and 10(-1) mM, respectively. There were differences in growth induction kinetics and in the rate of promotion. These results were further verified by treating the co-culture with adenylate cyclase activator, pNHppG, cAMP phosphodiesterase activators, imidazole and A23187, and cAMP phosphodiesterase inhibitors, IBMX, compound 48/80, and theophylline, separately. When the cytosolic cAMP levels increased by the reagents mentioned above, Toxoplasma in the cytoplasm of HL-60 cells stimulated to proliferate more rapidly with concentration-dependent modes compared to the control, and vice versa. It is suggested that some mechanisms are activated by the high levels of cAMP in the cytoplasm, which result in the stimulation of Toxoplasma proliferation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Effects of pyrimidine salvage inhibitors on uracil incorporation of Toxoplasma gondii.

Metabolic inhibitors which act in the process of pyrimidine salvage influenced on the uracil incorporation into nucleic acids of Toxoplasma. Inhibitors of dihydrofolate reductase, pyrimethamine and methotrexate, and inhibitors of thymidylate synthase, fluoro-uridine, fluoro-dUMP and fluoro-uracil, diminished isotopic uracil uptake in dose-dependent manners. Azauridine which suppresses de novo pyrimidine biosynthesis did not affect the salvage even in a relatively high dose. These results suggested that the activation of uracil salvage should be closely related with the function of TMP biosynthetic enzymes. The pattern of thymidine uptake had no differences between control HL-60 cells and Toxoplasma infected cells, which did not reflect the specific proliferation of Toxoplasma. It can be exploited to characterize the effects of various compounds related with the proliferation of Toxoplasma, especially its DNA synthesis.

Animals↗
PubMed1990

Tight junctional inhibition of entry of Toxoplasma gondii into MDCK cells.

Various conditions of cultures were performed to investigate the role of tight junctions formed between adjacent MDCK cells on the entry of Toxoplasma. When MDCK cells were cocultured with excess number of Toxoplasma at the seeding density of 1 x 10(5), 3 x 10(5), and 5 x 10(5) cells/ml for 4 days, the number of intracellular parasites decreased rapidly as the host cells reached saturation density, i.e., the formation of tight junctions. When the concentration of calcium in the media (1.8 mM in general) was shifted to 5 microM that resulted in the elimination of tight junction, the penetration of Toxoplasma increased about 2-fold (p less than 0.05) in the saturated culture, while that of non-saturated culture decreased by half. Trypsin-EDTA which was treated to conquer the tight junctions of saturated culture favored the entry of Toxoplasma about 2.5-fold (p less than 0.05) compared to the non-treated, while that of non-saturated culture decreased to about one fifth. It was suggested that the tight junctions of epithelial cells play a role as a barrier for the entry of Toxoplasma and Toxoplasma penetrate into host cells through membrane structure-specific, i.e., certain kind of receptors present on the basolateral rather than apical surface of MDCK cells.

Animals↗
PubMed1990

Clinical study of Marjolin's ulcer.

Marjolin's ulcer is the malignant lesion which develops in a burn scar or chronic fistula. Due to the low prevalence of this lesion, there has been disagreement regarding its clinical features, methods of treatment, and prognosis. We evaluated 19 cases of patients who had been admitted to Severance Hospital from Jan. 1970 to Dec. 1985. The results were as follows: The previous lesion was a burn scar in 52% of the cases and a fistula of chronic osteomyelitis in 32%. The mean latent period was 31.5 years. The initial symptoms were increased pain (74%), discharge with foul odor (68%) and bleeding (58%). Upon histological examination, all of the cases were squamous cell carcinoma. The rate of metastasis at the time of diagnosis was 32%. Of the 16 patients treated by surgery, local recurrence was noted in 4 cases. Three of these cases were patients who had been treated by excision and split thickness skin graft. The time interval for local recurrence ranged from 6 months to 11 months (average 8.8 months). In conclusion, the squamous cell carcinoma of marjolin's ulcer seems to have a worse prognosis than other squamous cell carcinomas and it requires aggressive treatment. The burn scar or chronic fistula that occurs in elderly patients especially requires more adequate treatment and close observation.

Adult↗
PubMed1989

Effect of ether lipids on mouse granulocyte-macrophage progenitor cells.

In this study we determined the potential bone marrow toxicity of the ether lipid derivatives 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine (OcMe-G-3-PC), 1-0-hexadecyl-propanediol-2-phosphocholine (He-Pr-2-PC), and hexadecylphosphocholine (He-PC). OcMe-G-3-PC inhibited the proliferation of mouse granulocyte-macrophage progenitor cells (GM-CFCs) at a dose of 1 micrograms/ml, whereas He-Pr-2-PC and He-PC started to inhibit the growth of hemopoietic precursors at 5 micrograms/ml. In contrast to this finding, NMRI mice given 10 mg/kg i.v. daily for 4 weeks and 20 or 30 mg/kg for 5 days showed no bone marrow toxicity. We conclude that the dose-dependent toxic effects observed in vitro are within the physiological tolerance in vivo.

Animals↗
PubMed1989

Hexadecylphosphocholine, a new ether lipid analogue. Studies on the antineoplastic activity in vitro and in vivo.

Hexadecylphosphocholine (He-PC) is a new compound synthesized according to the minimal structural requirements deducted from studies with other ether lipids. In vitro studies on He-PC revealed remarkable antineoplastic activity on HL60, U937, Raji and K562 leukemia cell lines. In addition, He-PC, applied orally, showed a superior effect in the treatment of dimethylbenzanthracene-induced rat mammary carcinomas when compared to intravenously administered cyclophosphamide. After oral application He-PC was well absorbed from the intestine and metabolized in the liver by phospholipases C and D. During a 5-week treatment no hematotoxic effects were detected. In a clinical pilot study on breast cancer patients with widespread skin involvement, topically applied He-PC showed skin tumor regressions without local or systemic side effects.

Animals↗
PubMed1989

Immunomodulation therapy for severe aplastic anemia--ALG versus ALG plus cyclosporin A.

Immunosuppressive treatment of aplastic anemia has been increasingly used as an alternative treatment to bone marrow transplantation. In this study, the additive effect of Cyclosporin A (CSA) (5mg/kg/day, at least 3 months) for maintenance of immunosuppression after antilymphocyte globulin (ALG) therapy (40mg/kg/day for 4 days) was compared to the previous ALG alone treatment (15mg/kg/day for 10 days). A high dose of methylprednisolone (20mg/kg/day for 5 days and 10mg/kg/day for 5 days) to the ALG group and a low dose of methylprednisolone (2mg/kg/day for 5 days) to the ALG plus CSA group were administered simultaneously. The results were as follows: 1) Sixteen (69.6%) out of twenty-three patients treated with ALG plus Cyclosporin A showed higher responses (CR: 48%, PR: 22%). On the contrary, nine out of nineteen in the ALG group showed lower responses (CR: 21%, PR: 26%). 2) Our data showed a tendency that male patients in age ranging from sixteen to thirty years showed an excellent response to ALG therapy (12/23: 52.2%). 3) The ALG plus CSA group revealed a faster response compared to the ALG alone group (15/16 within 6 months). 4) We speculate that ALG plus CSA therapy might be the treatment of choice for patients with a moderate degree of aplastic anemia. 5) Adding CSA to ALG increased the chance of infection, such as those with URI-like symptoms, but it did not affect the mortality rate. Our data suggest that the ALG plus CSA regimen may be a more useful therapeutic modality for patients with severe aplastic anemia who cannot be candidates for bone marrow transplantation and a randomized multicenter study is needed for confirmation of our preliminary study.

Adolescent↗