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Biomedical subjects

M Kozaki

Publications and source records attributed to M Kozaki.

At least 73 records · Page 4Linked to original sources
PubMed1991

Role of altered prednisolone-specific lymphocyte sensitivity in chronic renal failure as a pharmacodynamic marker of acute allograft rejection after kidney transplantation.

The effects of four immunosuppressive agents on the in vitro blastogenesis of peripheral blood lymphocytes activated by concanavalin A have been studied using cells from 26 healthy subjects, 34 patients with chronic renal failure (CRF) and 30 kidney transplant recipients. Differences in lymphocyte sensitivity to prednisolone between the healthy subjects and the CRF patients were statistically significant (P less than 0.0002), with impaired sensitivity in CRF. Impaired lymphocyte sensitivity occurred in 3.8% and 52.9% of the healthy and CRF subjects, respectively. Lymphocyte sensitivity to prednisolone, both preoperatively and 3 months post-operatively, was strongly correlated with early allograft rejection during co-administration of prednisolone with cyclosporin or azathioprine. Lymphocyte sensitivity to cyclosporin, azathioprine, and mizoribine in CRF was not significantly less than that in healthy subjects. Since the pharmacokinetics of prednisolone are little altered in renal transplantation, it is concluded that lymphocyte sensitivity specific to prednisolone may be a pharmacodynamic marker characteristic of successful graft survival in patients with histo-incompatibility and/or drug resistance.

Adult↗
PubMed1991

Impaired prednisolone sensitivities of the endocrine system and peripheral-blood lymphocytes are closely related to clinical incidence in renal transplantation.

Endocrine- and immune-responses to prednisolone and their relation to clinical incidence were assessed in 19 renal transplant recipients. All of the patients were treated with prednisolone and cyclosporin. Response of the hypothalamic-pituitary-adrenal (HPA) system to prednisolone was evaluated by measuring serum cortisol concentration. Cortisol concentration before transplantation was 126.7 +/- 38.6 ng mL-1, while it decreased to 4.1 +/- 2.5 ng mL-1 within the period characterized by a cumulative dose of prednisolone from 300 to 700 mg. A statistically significant high incidence (P less than 0.01) of acute rejections was observed in low HPA responders; (mean cortisol concentration during prednisolone treatment exceeded 3.0 ng mL-1), 6 of 12 with a low HPA response to prednisolone showed signs of rejection, while none of the 7 with a high HPA response showed signs of rejection. The concentrations of prednisolone suppressing the in-vitro response of pretransplant lymphocytes to concanavalin A by 50% (ID50) were determined. Lymphocytes from 8 patients were extremely insensitive (ID50 greater than 500 ng mL-1), and 5 of the 8 showed signs of rejection. Lymphocytes from the other 11 patients showed high sensitivity (ID50 less than 500 ng mL-1), and only one of those showed signs of rejection. Thus, a significantly high incidence of rejection was observed in low lymphocyte-responders to prednisolone (P less than 0.05). The results suggest that an insensitive endocrine response to prednisolone correlates with an impaired lymphocyte response to the steroid, and that both of the indices are related to occurrence of rejection. Evaluation of these pharmacodynamic parameters in combination may serve as a guideline for successful immunosuppressive therapy in renal transplantation.

Adult↗
PubMed1991

Recovery of decreased ability of peripheral-blood mononuclear cells from chronic renal failure to produce interleukin-1 alpha and beta after renal transplantation.

The ability of cultured peripheral-blood mononuclear cells (PBMC) to release interleukin-1 alpha and beta (IL-1 alpha, IL-1 beta) in response to concanavalin A (con A) was investigated in patients with chronic renal failure (CRF) and in renal transplant recipients. Mean IL-1 alpha level released by PBMC of healthy subjects (n = 42), CRF patients (n = 42), or transplants 2 months after operation (n = 69) was 152 +/- 103, 110 +/- 80, or 154 +/- 87 pg/5 x 10(5) cells/ml culture, respectively. IL-1 alpha release from PBMC of recipients 2 months after renal transplantation was significantly higher than that of CRF patients (p less than 0.05). Mean IL-1 beta level released by PBMC of healthy subjects (n = 34), CRF (n = 30), or transplants (n = 55) was 223 +/- 159, 135 +/- 129, or 276 +/- 155 pg/5 x 10(5) cells, respectively. Similar to IL-1 alpha, the level in CRF was significantly lower than that in healthy subjects (p less than 0.05). A time course study indicated that the ability of PBMC from transplants to release IL-1 alpha and beta promptly decreased following the operation, possibly owing to prednisolone and ciclosporin immunosuppressive therapy. However, after maintaining a low level for 2-3 weeks, IL-1 release from PBMC gradually increased thereafter. The results were consistent with known characteristics of decreased immunity in CRF states, and further suggested that the decreased ability of PBMC to release IL-1 alpha and beta in response to con A in CRF patients is recovered 2 months after renal transplantation.

Adult↗
PubMed1990

Suppression of endogenous cortisol for evaluating pharmacodynamics of prednisolone in early allograft rejection in renal transplantation.

Concentrations of endogenous cortisol were examined in 34 kidney-transplant recipients by improved "high-performance" liquid chromatography. Ten recipients were treated with prednisolone and azathioprine, the others with prednisolone and cyclosporine. Peripheral serum samples were collected just before transplantation, daily for two weeks after the transplant, weekly until discharge for about two months, and then monthly or occasionally. Mean (+/- SD) cortisol concentrations, initially 145 +/- 87 micrograms/L, decreased immediately to 5.93 +/- 5.11 micrograms/L after transplant, remained at almost these same values for two months, and then swiftly increased to 51 +/- 59 micrograms/L by 1000 days. Cortisol concentrations within the period characterized by a cumulative dose of prednisolone at 300-700 mg were correlated significantly with the presence or absence of acute allograft rejection; patients with cortisol greater than 4 micrograms/L had a higher risk of rejection. The majority of stable patients showed cortisol concentrations between 1 and 4 micrograms/L throughout the cumulative prednisolone period characterized above. Concentrations less than 1 microgram/L after high-dose administration of methylprednisolone were accompanied by severe lung infection. We conclude that suppressed concentrations of endogenous cortisol, as assessed by highly specific HPLC, might provide a basis for predicting the therapeutic efficacy and adverse effects of prednisolone.

Adult↗
PubMed1990

[Anti neutrophil cytoplasm antibody in Wegener's granulomatosis].

Autoantibodies against human neutrophil cytoplasma (ACPA) were assayed in 50 serum samples from patients with systemic vasculitic syndrome by indirect immunofluorescence method. ACPA titer was higher than 32x in 5 patients with active Wegener's granulomatosis (WG) although ACPA of low titer was found in 2 patients with AGA, 1 patient with temporal arteritis. It was confirmed that serial changes of ACPA titer in 5 patients with WG proved to be the selective marker of disease activity and the severity of renal injury in WG. It was concluded that the detection of ACPA is useful both for the early diagnosis and monitoring the activity of WG.

Adult↗
PubMed1989

Determination of cyclosporin A in the serum of kidney transplant patients by rapid-flow fractionation and normal-phase high-performance liquid chromatography.

High-performance liquid chromatography was used to determine cyclosporin A (CsA) concentrations in the serum of kidney transplant patients by rapid-flow fractionation (RFF) followed by silica gel normal-phase high-performance liquid chromatography (HPLC). The extraction of CsA from serum was achieved by RFF using a short diatomaceous earth column eluted with diethyl ether-n-hexane (50:50, v/v). The recovery was more than 80% at concentrations of 50-150 micrograms/l. The concentration of this compound was determined by HPLC using a conventional silica gel column with 3.3 M ammonia solution-ethanol-n-hexane (0.31:10.69:89, v/v) as eluent. Concentration calibration was made on the basis of the peak-height ratio of CsA to CsD as the internal standard. The coefficient of variation of this assay was less than 6.5% and the results were used for the therapeutic drug monitoring of CsA administered to kidney transplant patients. Measurements of the CsA concentrations in 160 serum specimens were also made by conventional radioimmunoassay (RIA) using commercial kits. The data obtained by RIA were on average 2.5 times those obtained by HPLC. Higher values in RIA were observed characteristically with patients with severe disfunction resulting from CsA hepatotoxicity. From the results, it appeared that HPLC rather than RIA provides more precise and reliable values for the concentration of this drug.

Adult↗