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Biomedical subjects

T Isobe

Publications and source records attributed to T Isobe.

334 records · Page 19Linked to original sources
PubMedDate not supplied

Effect of age on human peripheral blood stem cells.

We evaluated the correlation between the number of peripheral blood stem cells (PBSCs) and aging by monitoring those of CD34+ cells (PB-CD34+), colony-forming unit granulocyte macrophages (PB-CFU-GM) per 1 ml of peripheral blood in normal volunteers (n=50) including 20 males and 30 females (median age 67, range 20-90). The numbers of PB-CD34+, PB-CFU-GM were monitored by flow cytometry and methylcellulose-based colony assay, respectively. An inverse correlation between the number of PB-CD34+ with age (r=-0.33, p=0.020) was found. Furthermore, the number of PB-CFU-GM also showed an inverse correlation with age (r=-0.58, p=0.003). Based on these results, it is suggested that the number of PBSCs decrease with age.

Adult↗
PubMedDate not supplied

The relationship between carboplatin AUC and serum thrombopoietin kinetics in patients with lung cancer.

To clarify the relationship between the carboplatin AUC and the extent of damage to thrombopoiesis, we monitored both endogenous serum TPO kinetics and carboplatin pharmacokinetics after single-agent carboplatin administration. Previously untreated 12 patients with stage IV non-small-cell lung cancer were enrolled. The actual carboplatin AUC showed a significant positive correlation with the maximum increase ratio of TPO (TPOmax/TPOday1) (r = 0.74, p = 0.014). Furthermore, the increase ratio of TPO at one week after administration of carboplatin (TPOday8/TPOday1) showed a significant negative correlation with the following platelet nadir around day 19 (r = -0.84, p = 0.005). By monitoring the changes in endogenous TPO concentration, we could estimate the degree of thrombocytopenia and determine the indication, and thus the optimal timing of prophylactic administration of TPO before platelets are markedly reduced.

Adenocarcinoma↗
PubMedDate not supplied

Carboplatin AUC and gamma-glutamylcysteine synthetase gene expression in peripheral mononuclear cells of lung cancer patients.

BACKGROUND: To investigate the association between glutathione-related enzymes and carboplatin (CBDCA) dose, we examined gene expression levels for both subunits of gamma-glutamylcysteine synthetase (heavy; gamma-GCSh, light; gamma-GCS1) in peripheral mononuclear cells (PMN) of lung cancer patients before and after CBDCA administration. MATERIALS AND METHODS: PMN and plasma samples were obtained from 10 advanced non-small lung cancer patients before and after CBDCA administration. We analyzed the gene expression levels by reverse transcription-polymerase chain reaction. RESULTS: Gamma-GCSh expression levels in PMN increased within 24 hours after CBDCA administration, whereas gamma-GCS1 expression levels did not. However, the actual area under the concentration curve (AUC) of CBDCA did not correlate with gamma-GCSh expression at 24 hours or the increased ratio of gamma-GCSh expression in PMN. CONCLUSION: Expression of gamma-GCSh is induced by CBDCA, however, CBDCA AUC is not a determinant for the increased expression levels of gamma-GCSh in PMN.

Antineoplastic Agents↗
PubMedDate not supplied

Effects of corticosteroids on lymphocyte subpopulations and lymphokine secretion in chickens.

Various effects of glucocorticosteroids on the avian immune system were examined in chickens treated intramuscularly with 0.1 to 2.5 mg dexamethasone or prednisolone. Kinetic changes in body weight gain, percentages of lymphocyte subpopulations, and T-cell functions were examined following treatment with dexamethasone or prednisolone every other day. Chickens treated with dexamethasone or prednisolone showed a decrease in body-weight gain compared with age-matched, untreated chickens. In general, the total number of splenic lymphocytes of chickens treated with the two drugs was significantly lower than in controls in a dose-dependent manner. Flow cytometric analysis of splenic lymphocyte subpopulations revealed that the percentages of lymphocytes expressing CD8, gamma delta T-cell receptor, Ia, or IgM antigens and natural killer cells were lower in dexamethasone-treated chickens than in the controls, whereas the percentages of T lymphocytes bearing CD3, CD4, or alpha beta TCR antigens were higher. Furthermore, splenic T cells obtained from dexamethasone-treated chickens showed a significant depression in concanavalin A-induced lymphoproliferation and interleukin 2 and gamma-interferon production. The results characterize a variety of immunosuppressive effects of glucocorticoids on the avian immune system.

Animals↗
PubMedDate not supplied

Protection against chicken leucocytozoonosis provided by immunization with spleen homogenate infected with Leucocytozoon caulleryi.

Protection against chicken leucocytozoonosis was assessed in chickens immunized with spleen homogenates from chickens that had received sporozoites of Leucocytozoon caulleryi 7 or 13 days previously. Chickens immunized with the homogenate were challenged with sporozoites of L. caulleryi and observed for changes in clinical signs, parasitemia, serum-soluble antigen, and antibody responses. In chickens immunized with either the 7-day or 13-day homogenate, clinical signs and parasitemia were moderate, mild or absent. This was the case both after immunization with the homogenate and after sporozoite challenge. Immunization with spleen homogenates demonstrated protection against chicken leucocytozoonosis.

Animals↗
PubMedDate not supplied

Resistance of chicks against reinfection with Leucocytozoon caulleryi.

Chickens were inoculated with five to 40 sporozoites of Leucocytozoon caulleryi at 1 to 9 days of age. Mortality, parasitemia, appearance of serum-soluble antigen, and antibodies were examined. Chickens that survived primary infection were reinoculated with 3 x 10(3) to 1 x 10(4) sporozoites and examined for resistance against reinfection by the same criteria used in primary infection. After primary infection, up to 80% of chickens died of leucocytozoonosis. Surviving chickens showed parasitemia from 13 days to 23 or 24 days after inoculation. Serum-soluble antigen and antibodies were detected in most chickens, except for some chickens that were infected at 1 to 3 days of age. After secondary infection, only a few chickens that received primary infection at 1 to 7 days of age showed a small number of parasites in their peripheral blood. Most of the other chickens were resistant to reinfection. Resistance to reinfection was recognized in some chickens that had not showed antibody production before secondary infection.

Age Factors↗
PubMedDate not supplied

Limited-sampling models for estimation of the carboplatin area under the curve.

BACKGROUND: The area under the curve (AUC) of free carboplatin, is a major determinant of toxicity and response. A conventional pharmacokinetic study to determine AUC requires frequent blood sampling. One strategy for overcoming this problem is to apply a limited sampling model (LSM). MATERIALS AND METHODS: We developed LSMs by stepwise forward multiple regression analysis using 27 data series from 24 patients with lung cancer (training data set) who received carboplatin in combination with oral etoposide. The models were then validated using 24 data series from 18 patients (test data set). RESULTS: In the test data set, the single-sample model was confirmed to give excellent estimation of the AUC: AUC (mg/ml x min) = 0.93 x C3h + 0.47 (MPE% = 4.4%, RMSE% = 8.9%). Furthermore, the two-sample model was shown to improve both the bias and precision of AUC estimation: AUC = 0.16 x C1h + 2.26 x C8h + 0.75 (MPE% = 0.9%, RMSE% = 5.3%). CONCLUSIONS: Our models are useful for future trials to define the accurate relationships between the dose-intensity and effect of carboplatin.

Adenocarcinoma↗
PubMedDate not supplied

Mobilization of peripheral blood stem cells in patients with advanced thoracic malignancies after irinotecan (CPT-11) administration.

We evaluated the mobilization of peripheral blood stem cells (PBSCs) after the administration of chemotherapy including irinotecan (CPT-11) in individuals with advanced thoracic malignancies including lung cancer and mesothelioma. All patients were previously untreated. The numbers of CD34+ cells, CD34+ 38- cells, and colony-forming units granulocyte-macrophage (CFU-GM) in peripheral blood were determined to monitor PBSCs at least twice a week. Granulocyte colony-stimulating factor (G-CSF) (75 micrograms/body per day) was administered at the onset of neutropenia [absolute neutrophil count (ANC) of < 1000/microliter] until the ANC exceeded 5000/microliter. In patients who received G-CSF, sufficient counts of the PBSCs for PBSC transplantation were mobilized at the time when the white blood cell count was > 5000/microliter. CPT-11 with G-CSF is thus a promising induction regimen for PBSC transplantation. Patients who did not develop neutropenia after chemotherapy showed a significantly (p = 0.005) higher number of CD34+ cells in the peripheral blood at steady state (median, 1818; range, 1534 to 4433; n = 8) than those who developed neutropenia (median, 666; range, 608 to 1553; n = 5). This parameter may thus prove a useful marker for predicting neutropenia after the administration of CPT-11.

ADP-ribosyl Cyclase↗
PubMedDate not supplied

Expression of lung-resistance protein gene is not associated with platinum drug exposure in lung cancer.

BACKGROUND: Platinum drug resistance is an important problem in lung cancer chemotherapy. In this study, we examined lung-resistance protein (LRP) gene expression in vivo and in vitro in relation to platinum drug exposure. MATERIALS AND METHODS: The expression levels of the LRP gene were assessed by the reverse transcription polymerase chain reaction, in 80 autopsy samples (40 lung tumors and 40 corresponding normal lung tissues), two lung cancer cell lines and in peripheral mononuclear cells collected from 8 lung cancer patients before and after platinum drug administration. RESULTS: The LRP gene expression levels of autopsy specimens exposed antemortem to platinum drugs were not significantly different to those of specimens without platinum drug exposure, for both lung tumors and normal lung tissues. Our results also demonstrate that LRP gene expression was not induced by platinum drugs either in vitro or in vivo. CONCLUSIONS: The present results indicate that LRP gene expression is not associated with platinum drug exposure in lung cancer.

Adenocarcinoma↗