Effects of lipid ingestion on the induction of drug metabolizing enzymes of nuclear envelope and microsomes by phenobarbital.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
K C Cheng
Publications and source records attributed to K C Cheng.
Pyrazoles. I. Synthesis of 4-hydroxypyrazolo[3,4-d]-v-triazine. A new analog of hypoxanthine.
Explore the source record for details and available documents.
Allopurinol↗
Clonal expansion of T-cell receptor beta gene segment in the retrocochlear lesions of EAE mice.
It has been reported that the T cell receptor V beta 8.2 (TcrbV8.2) gene segment is predominantly expressed in encephalomyelitic T cells responding to myelin basic protein (MBP) in experimental allergic encephalomyelitis (EAE) mice. We have demonstrated retrocochlear hearing loss in EAE mice in previous studies. Administration of a monoclonal antibody specific to the T cell receptor V beta 8 (TcrbV8) subfamily prevented both this type of hearing loss and the central nerve disease. In this study, we examined the role of the TcrbV8.2 gene segment in the retrocochlear lesions of EAE mice. A clonal expression of T cell receptor beta chain gene segment (TcrbV8.2-TcrbD2-TcrbJ2.7) was identified in the retrocochlear lesions. The TcrbV8.2 gene segment appears to recombine only with TcrbJ2.1 (32.1%) and TcrbJ2.7 (67.9%) gene segments. The TcrbJ2.7 gene segment has also been previously identified as the dominant TcrbJ gene in the lymph nodes of EAE mice. Only TcrbD2, with a length of 4 amino acids, was observed recombining with these TcrbV8.2 sequences. G and C nucleotides are predominantly expressed at the N regions between the V-D and D-J junctions. This dominant TcrbV gene segment (TcrbV8.2-TcrbD2-TcrbJ2.7) observed in the retrocochlear lesions has been identified in the MBP-specific T cells from the lymph nodes of EAE mice. These results suggest that a small subset of antigen-specific T cells migrate to, and expand at, the retrocochlear lesions, which leads to hearing loss.
Amino Acid Sequence↗
Antibodies against inner-ear proteins in the sera of patients with inner-ear diseases.
Sera from patients with various inner-ear diseases, especially Ménière's disease, were investigated by Western blot against guinea pig inner-ear proteins. Of 45 patients, 24 (53%) with various inner-ear diseases had antibodies against inner-ear proteins, compared with 0 of 10 (0%) in control subjects without inner-ear diseases. Of the 10 proteins that showed a positive reaction with patient sera, the 28-kD band was unique in that it appeared only in the membranous fraction of the inner ear and was highly positive (28%) in reaction with Ménière's disease patient sera. The results in the present study with proteins extracted from guinea pig inner ear were consistent with our previous study using proteins from human inner ear, suggesting that the 28-kD protein may be a candidate for detecting autoimmune inner-ear disease.
Animals↗
Molecular basis of type II collagen autoimmune disease: observations of arthritis, auricular chondritis and tympanitis in mice.
A type II collagen autoimmune response results in arthritis, auricular chondritis and tympanosclerosis in humans and animals. The purpose of this study is to further define the molecular and pathogenic events involved in these lesions in rodents. Type II collagen fragment CB11-specific monoclonal antibodies induced lesions in joints, ear lobes and tympanic membranes. In immunized mice, the thickness of tympanic membranes increased to two- to fourfold normal size. Electron micrography showed that the arrangement of collagen fibers is irregular in both radial and auricular layers, containing fibroblasts, a homogeneous material resembling low-density cholesterol crystals and cell infiltration. The mice with auricular chondritis had lymphocytes expressing V beta-8 T cell receptor (TCR) in arthritic joints and lymphocytes expressing V beta-6 TCR in ear lobe lesions. A monoclonal antibody specific to the TCR V beta-8 subfamily suppressed the onset of arthritis. Sequence analyses of the V beta structure of TCR involved in the lesions confirm the immunohistologic study.
Animals↗
Metabolism of progesterone and estradiol by microsomes and purified cytochrome P-450 RLM3 and RLM5.
The metabolism of progesterone and estradiol by cytochrome P-450 RLM3 and RLM5 and by male rat liver microsomes was compared. Products formed were identified by thin layer chromatography and by gas chromatography-mass spectrometry. Eleven metabolites were detected from progesterone metabolism. Three proved to be reduction products formed only by the microsomes and seven metabolites were identified. Those identified were 5 alpha-pregnane-3,20-dione, 3 beta-hydroxy-5 alpha-pregnane-20-one, 2 alpha-hydroxyprogesterone, 6 beta-hydroxyprogesterone, 6 alpha-hydroxyprogesterone, 15-hydroxyprogesterone, and 16 alpha-hydroxyprogesterone. RLM3 formed 6 beta- and 16 alpha-hydroxyprogesterone as major products and 6 alpha- and 15-hydroxyprogesterone as minor ones. RLM5, however, formed 2 alpha-hydroxy- and 16 alpha-hydroxyprogesterone as major products, and 6 beta-hydroxyprogesterone as a minor product. RLM5 and microsomes did not produce detectable levels of 15-hydroxyprogesterone. Two very polar metabolites were produced from progesterone by both RLM3 and RLM5 but were not seen with microsomes and were not identified. Four metabolites were formed from estradiol. One, 15-hydroxyestradiol, was formed only by RLM3. No other product was formed by this enzyme at appreciable rates. RLM5 and microsomes also formed estrone, estriol, and 2-hydroxyestradiol, but the first of these was a very minor product. This study clearly shows a stereospecificity and positional specificity in metabolism of steroid hormones by cytochrome P-450 isozymes of the untreated rat.
Animals↗