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Biomedical subjects

B Choi

Publications and source records attributed to B Choi.

9 recordsLinked to original sources

Characterization of catechol 2,3-dioxygenases.

Three catechol 2,3-dioxygenases for biphenyl, naphthalene/salicylate, and toluene/xylene oxidation were cloned from Achromobacter xylosoxidans KF701, Pseudomonas putida (NAH7), and Pseudomonas sp. (pWWO). The cloned catechol 2,3-dioxygenases were identified by enzymatic activity assay in addition to yellow bands on polyacrylamide gel after electrophoresis and activity staining. All of the cloned catechol 2,3-dioxygenases exhibited their highest activities on catechol as a substrate compared with catechol derivatives including 4-chlorocatechol, 3-methylcatechol, and 4-methylcatechol. The cloned catechol 2,3-dioxygenases are not fused proteins but were significantly different from one another in their electrophoretic mobilities on nondenaturing 7.5%-polyacrylamide gel.

Alcaligenes

Selective killing of glioma cells in culture and in vivo by retrovirus transfer of the herpes simplex virus thymidine kinase gene.

The thymidine kinase gene (tk) of herpes simplex type 1 virus (HSV-1) was inserted into a retroviral vector under the transcriptional control of the enhancer-promoter element of the Moloney murine leukemia virus long terminal repeat. Replication-defective viral particles were obtained by transfection of vector DNA into the packaging cell line psi2 and were used to infect C6 rat glioma-derived cell lines in culture. The sensitivity of these cells to the toxic effects of the nucleoside analog ganciclovir was found to be significantly increased by transfer of the HSV-1 tk gene. The difference in sensitivity between infected and uninfected cells defined ganciclovir concentrations that could be used to selectively kill essentially all infected cells while sparing uninfected ones. C6 glioma cells introduced subcutaneously into nude mice were highly tumorigenic. Growth of tumors produced from C6-derived cells bearing the HSV-1 tk gene, but not parental C6 cells, could be inhibited by intraperitoneal administration of ganciclovir. This work demonstrates the effectiveness of the thymidine kinase expressed by the HSV-1 ks gene in sensitizing brain tumor cells to the toxic effects of nucleoside analogs. Retrovirus vectors should thus prove useful in the selective delivery of this killer gene to dividing tumor cells in the nervous system, where most endogenous cells are not dividing.

Animals

Inhibition of growth and angiogenesis of human neurofibrosarcoma by heparin and hydrocortisone.

A human neurofibrosarcoma was removed at surgery from a patient with neurofibromatosis and implanted into the subrenal capsule of female nude mice (nu/nu). A solid tumor grew and was transferred to 78 additional mice for this study. The animals were randomly assigned to one of four groups: 1) control, 27 animals; 2) oral heparin (200 or 500 U/ml), 17 animals; 3) oral hydrocortisone (0.3 mg/ml), 10 animals; or 4) oral heparin (200, 500, or 1000 U/ml) with hydrocortisone (0.3 mg/ml), 24 animals. After 10 days of treatment, the animals were sacrificed and the tumor size and degree of neovascularization were compared to the pretreatment data. Heparin treatment alone stimulated angiogenesis and resulted in tumor growth greater than in the control group (p less than 0.001). Administration of hydrocortisone alone caused a minimal reduction in tumor growth and had a minimal effect on angiogenesis (p less than 0.05 vs. control group). In contrast, heparin administered with hydrocortisone inhibited both angiogenesis and tumor growth (p less than 0.001 vs. control group). These studies suggest that angiogenesis modulators are worthy of further study as feasible means of treating human neurofibrosarcoma.

Animals

Dietary fat effects on the initiation and promotion of two-stage skin tumorigenesis in the SENCAR mouse.

We investigated the influence of dietary corn oil on initiation of skin tumors in SENCAR mice with 7,12-dimethylbenz(a)anthracene (DMBA) (10 nmol at 8 to 9 wk of age) and the promotion of these tumors with 12-O-tetradecanoylphorbol-13-acetate (TPA) (3.2 nmol twice weekly for 20 wk). Diet high in corn oil (24.6%) was fed, in comparison with control diet (5%), to mice during two time schedules: (a) high-fat diet was fed preceding and for 1 wk following DMBA to assess the effects of high corn oil diet on initiation; and (b) high-fat diet was fed starting at the time of the first TPA treatment (1 wk following DMBA initiation) until the end of the experiment to assess effects of high corn oil diet on promotion. Mice were trained to consume equivalent caloric allotments of the low- and high-fat diets to ensure that the observed effects on tumor development were for dietary fat at constant calorie intake. Feeding high corn oil diet during DMBA treatment did not influence the incidence of skin papilloma or carcinoma, but the number of papillomas per effective mouse was reduced in mice fed the high-fat diet during initiation. Consumption of the high corn oil diet during and following TPA treatment resulted in an increase in the incidence of papillomas up until Wk 14 of the experiment, an increase in the number of papillomas per effective mouse throughout the experiment, and an increase in the number of carcinomas per effective mouse during Wk 25 to 34. However, cumulative carcinoma yield (Wk 25-44) did not differ between the diet groups. Dietary treatment did not influence food consumption, body weight, or survival in the mice treated with DMBA and TPA. Northern blot hybridization studies were carried out on RNA purified from tumors of high- and low-fat mice to determine if diet influenced the pattern of Ha-ras oncogene expression. The results of this experiment indicated that elevated levels of Ha-ras-specific RNA, in comparison with normal epidermal RNA, were present in papillomas and carcinomas from DMBA-initiated, TPA-promoted mice irrespective of the diet the mice were fed.

9,10-Dimethyl-1,2-benzanthracene

The induction of intercellular adhesion molecule 1 (ICAM-1) expression on human fetal astrocytes by interferon-gamma, tumor necrosis factor alpha, lymphotoxin, and interleukin-1: relevance to intracerebral antigen presentation.

Antigen presentation reactions are dependent upon the expression of the class II major histocompatibility antigens (MHC), the T-cell receptor, and the presented antigen. Recent studies demonstrate that such processes also require the presence of adhesion molecules such as lymphocyte functional antigen 1 (LFA-1) and its cell surface ligand, intercellular adhesion molecule 1 (ICAM-1). It has been suggested that the brain astrocyte can function as a facultative antigen presenting cell (APC). This hypothesis is based upon the ability to induce the expression of the class II MHC antigens on astrocytes, and on their ability to present myelin basic protein to encephalitogenic T-cells in vitro. The best in vivo data showing that astrocytes serve as intracerebral APCs is the finding that astrocytes in multiple sclerosis plaques are DR+ (class II MHC in human). However, it still remains to be resolved whether the in vivo expression of the MHC antigens in disease states is instrumental to antigen presentation mechanisms or whether these cell surface glycoproteins are expressed secondary to brain immune responses. If astrocytes function as immunocompetent APCs within the brain, it would seem that they would also be able to express molecules important for intercellular adhesion. Here, we present the first data that indicates that human astrocytes are capable of expressing ICAM-1 in response to cytokines that either induce or upregulate the expression of DR. In essence, cytokines derived from different cell types seem to exert similar pleiotropic effects on the modulation of MHC and ICAM-1 expression on astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Presenting Cells

Meta-analysis.

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Research Design

Effect of isotretinoin on experimentally induced comedones.

The effect of isotretinoin on experimentally induced comedones was studied by means of histoplanimetry and scanning electron microscopy (SEM). To induce comedone formation, insoluble cutting oil was applied to the ventral surface of the ears of rabbits for 2 weeks. After comedones formed, isotretinoin was fed to the rabbits by a feeding tube, daily, for 4 weeks. A low dose (2.0 mg/kg) and a high dose (20.0 mg/kg body weight) were selected for two different groups. Soybean oil served as the vehicle. Histoplanimetrically, the high-dose group showed a significant decrease in size of comedones when compared to the control group and the low-dose group [P less than 0.005], and in the high-dose group, the follicular lumen contained a small number of loose, non-adherent, horny cells. Upon SEM examination, the comedones were seen to have a 'chrysanthemum' appearance before treatment. After treatment, the high- and low-dose groups both showed evidence of the elimination of comedones on three-dimensional analysis.

Acne Vulgaris

Primary pituitary carcinoma: a clinical pathological study.

A 60-year-old woman presented with a history of headache and rapidly progressive complete bilateral ophthalmoplegia. Her endocrine function was normal. Radiographic studies revealed signs of diffuse destruction of the sella turcica by a tumor without suprasellar extension. Biopsies of the lesion within the sphenoid sinus demonstrated the presence of a primary pituitary carcinoma; autopsy findings revealed metastatic deposits in the liver, kidney, and lung. The histological characteristics of these cells and the electron microscopic findings confirmed that the tumor can first manifest themselves by the rapid development of unilateral or bilateral ophthalmoplegia; this diagnosis should be considered in all individuals with such a syndrome.

Carcinoma