Biomedical subjects
Y Yuhki
Publications and source records attributed to Y Yuhki.
[Cyclosporine level in blood as monitored by area-under-the-curve (AUC). III. The influence of absorption phase after orally dosing].
The influence of the absorption phase (the time of maximum blood concentration; Tmax) on the pharmacokinetics of cyclosporine (CYA) in the steady state after oral administration was studied in 26 renal transplant recipients. The patients were divided into three absorption phase groups with the Tmax times as follows, group A (n = 26); OH < or = Tmax < 3 h, group B (n = 6); 3 h < or = Tmax < 6 h and group C (n = 11); 6 h < or = Tmax < or = 12 h. CYA (dose; 1.6-15.0 mg/kg/d) was administered orally to all 26 patients (10-52 years, 33.1-74.2 kg) every 12 h. The blood specimens used in this study were collected just before administration (0 h) in the morning and at intervals of 1, 2, 3, 6, 8 and 12 h after administration. The whole blood CYA levels were measured by high-performance liquid chromatography (HPLC) or by fluorescence polarization immunoassay (FPIA) based on a specific monoclonal antibody. There were no significant differences between the three groups in terms of the dosage (mg/kg/d) and area-under-the-curve (AUC). The trough levels (0, 12 h) correlated well to the AUC only in group A (r = 0.842-0.907, p < 0.001). The morning trough levels (0 h) were significantly higher than the night trough levels (12 h) in groups A and B (p < 0.05-0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
[The significance and problem of cyclosporine blood level monitoring].
Cyclosporine, a potent immunosuppressive agent used to prevent rejection of transplanted organs, has a narrow therapeutic range and various toxic effects, mostly concentration-dependent. The kinetics of this drug present a large intra- and interindividual variability due to many factors, resulting in marked variations of blood cyclosporine concentrations, and in a poor correlation between administered dose and concentration. The knowledge of cyclosporine peculiarities and of factors affecting blood concentrations can provide a rational basis for establishing an adequate therapy for the individual patient. Cyclosporine monitoring is a method of evaluating whether the therapeutic choice is correct. Cyclosporine concentrations can be measured in whole blood, plasma, and serum using radioimmunoassay (RIA), high-performance liquid chromatography (HPLC) or fluorescein polarization immunoassay (FPIA). Different results are obtained, depending on the technique and on the biological fluids used. Cyclosporine measurement presents many problems and difficulties. There is a need for standardization and for quality assessment programs. The recent development of monoclonal antibodies may represent a significant advance for cyclosporine monitoring. Therapeutic drug monitoring (TDM) should be undertaken on a regular basis after the initiation of therapy with cyclosporine.
Reduced DNase I sensitivity of the rearranged c-myc gene in somatic cell hybrids between murine plasmacytoma cells and fibroblasts.
In mouse plasmacytoma (MPC) S194, the rearranged c-myc gene was much more sensitive to DNase I digestion than the nonrearranged gene. The sensitivity of the rearranged c-myc was markedly reduced to the same extent as that of the nonrearranged one in hybrids between the MPC cells and the fibroblasts, but not in a hybrid between the MPC and the spleen cells. These results suggest that trans-acting factors in fibroblasts alter the DNase I-sensitive structure of the rearranged c-myc gene.
c-myc expression and transformed phenotypes in hybrid clones between mouse plasmacytoma S194 cells and normal spleen cells or fibroblasts.
Expression of the rearranged c-myc oncogene and transformed phenotypes was investigated in 2 different types of somatic cell hybrid clones between a BALB/c mouse plasmacytoma line (S194) and normal allogeneic spleen cells or fibroblasts. In the parental S194 cells, one allele of the c-myc was rearranged and its 5'-flanking region was partially deleted by recombination with the immunoglobulin C alpha gene. Due to this recombination, S194 cells expressed approximately 20-fold higher than normal spleen or fibroblast levels of c-myc transcripts from the rearranged allele, which are smaller than normal germ-line 2.4-kb c-myc transcripts, but they expressed the same low levels of 2.4-kb c-myc transcripts from the non-rearranged allele as compared with normal spleen cells or fibroblasts. All the hybrid clones retained both the rearranged and the non-rearranged c-myc. The hybrid clones between S194 and normal spleen cells showed transformed phenotypes and expressed the same high levels of rearranged c-myc transcripts and low levels of the non-rearranged c-myc transcripts as the parental S194 cells. On the other hand, the hybrid clones between S194 cells and normal fibroblasts showing non-transformed phenotypes inhibited expression of the rear-ranged c-myc to undetectable levels but expressed the non-rearranged c-myc transcripts at low levels. A hybrid clone between S194 cells and normal fibroblasts showing transformed phenotypes also exhibited the same pattern of c-myc expression as the non-transformed hybrid clones. These results indicate that expression of the rearranged c-myc in S194 mouse plasmacytoma cells is modulated in different ways in different components of cell lineages, although the correlation between the levels of rearranged c-myc transcripts and the transformed phenotypes in the hybrid clones was not absolute.
High-performance liquid chromatographic determination of tranilast in plasma.
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