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Biomedical subjects

N Deguchi

Publications and source records attributed to N Deguchi.

At least 91 records · Page 5Linked to original sources
PubMed1987

[Comparative study of the activating effects of recombinant human interleukin 2 and interferon-gamma on cell-mediated cytotoxicity against renal cell carcinoma in vitro].

The effects of recombinant interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) on lymphocyte-mediated cytotoxicity against established human renal carcinoma cell lines KU-2 and Caki 1, and freshly prepared human renal carcinoma cells were compared in vitro. After incubation of peripheral blood lymphocytes from normal adult volunteers with IL-2 and IFN-gamma over a range of concentrations, cytotoxicity was determined by 4-h 51Cr-release assay. Augmentation of cytotoxicity by IL-2 and IFN-gamma was dose-and time-dependent. IL-2 induced significantly greater cytotoxicity against renal carcinoma cells than did IFN-gamma. The optimal dose of IL-2 was 100 to 500 units/ml, and cytotoxicity was increased even at concentrations as low as 4 units/ml. The results indicated that the systemic administration of IL-2 to patients will be effective for treatment of renal cell carcinoma which is resistant to interferon therapy. A continuous infusion or multiple repeated bolus doses over a period of one day, however, should be considered in order to maintain high levels of IL-2 in the serum.

Adult↗
PubMed1987

[Clinical studies of gamma-seminoprotein in prostatic disease. II. Immunohistochemical study of gamma-seminoprotein].

Localization of gamma-seminoprotein (gamma-Sm) was examined using horseradish peroxidase-labeled anti-gamma-Sm antibody (Chugai Corp. Ltd., Tokyo, Japan) by the enzyme-labeled antibody method in paraffin embedded specimens of 18 benign prostatic hyperplasias and 32 untreated prostatic cancers. The level of serum gamma-Sm was also determined by enzyme immunoassay in 10 untreated patients with prostatic cancer and 18 with benign prostatic hyperplasia. Specific gamma-Sm staining was detected in prostatic glandular epithelial cells and prostatic secretion of all specimens of benign prostatic hyperplasias and a half of the specimens of prostatic cancers. Specific gamma-Sm staining was shown to correlate with histological differentiation of the prostatic cancer, but no correlation was found between specific gamma-Sm staining and the level of serum gamma-Sm.

Adenocarcinoma↗
PubMed1987

[Cyclophosphamide, adriamycin and cisplatinum combination chemotherapy for advanced urothelial and prostatic carcinoma].

Between 1980 and 1985, 17 patients with advanced urothelial carcinoma and 13 with metastatic prostatic carcinoma refractory to hormonal therapy were treated with a combination chemotherapy of cyclophosphamide (CPM), adriamycin (ADM) and cis-diammine-dichloroplatinum (CDDP) to evaluate its antitumor effect and toxicity. ADM (1 mg/kg) on day 1, CPM (2 mg/kg) on days 2 through 5 and CDDP (1.5 mg/kg) on days 6 and 7 were administered every 3 weeks. Of the 17 patients with urothelial carcinoma, 13 were eligible for evaluation. One patient achieved CR with a disease-free interval lasting for 29 months, one showed PR (duration of response 2 months), 4 NC and 7 PD, with an overall response rate of 15% (2/13). Of the 13 patients with prostatic carcinoma, 11 could be evaluated. No patients achieved CR, one had PR (duration of response 5 months), 2 NC and 8 PD, with an overall response rate of 9% (1/11). No statistically significant difference in survival was noted between responders (CR + PR) and non-responders (NC + PD) to the combination chemotherapy, irrespective of whether they had metastatic urothelial or prostatic carcinoma. Myelosuppression was frequently noted, with sepsis occurring in one patient. No mortality attributable directly to this regimen was noted.

Aged↗
PubMed1986

Age-dependent propranolol clearance in perfused rat liver.

The effect of age on the hepatic clearance of propranolol was studied by perfusing the liver isolated from 3- to 104-week-old rats. Propranolol levels in the recirculating perfusate declined biexponentially with time in all age groups. When the liver isolated from 7-week-old rats was perfused with propranolol (1 microgram/ml, 100 ml), hepatic clearance of this drug by the perfused liver (CLperf) increased from 0.589 to 1.14 ml X min-1 X (g liver)-1 with the increase of the perfusion flow rate from 1.0 to 2.0 ml X min-1 X (g liver)-1, confirming evidence of "perfusion-limited" hepatic clearance for this drug. Furthermore, there was no initial concentration(dose)-dependence in CLperf up to 2.5 micrograms/ml (i.e. 250 micrograms/organ). The effect of age on CLperf was then investigated by perfusing the isolated liver with 1.0 micrograms/ml propranolol at 2.0 ml X min-1 X (g liver)-1. Elimination of this drug from the perfusion medium was relatively rapid in 5- to 7-week-old rats, yielding the highest CLperf in these relatively young rats [approximately 1.0 to 1.1 ml X min-1 X (g liver)-1]. In contrast, CLperf values in both immature and older rats were 0.5 ml X min-1 X (g liver)-1 or less. The in vitro intrinsic hepatic clearance estimated in 5- and 7-week-old rats was about ten times as high as that in 104-week-old rats.

Aging↗
PubMed1986

[Sequential combination therapy with alpha interferon and OK-432 (streptococcal preparation) against advanced renal cell carcinoma].

Renal cell carcinoma (RCC) is one of the most insensitive urologic tumors to either radiotherapy or anticancer chemotherapy. Recently, effectiveness of interferon (IFN) against RCC has been reported. However, because this effect is somewhat limited, a new modality of treatment is needed. We herein report our experience with IFN and OK-432, a streptococcal preparation for patients with advanced RCC. Twenty patients aged from 26 years to 75 years, with an average age of 52.3 years, were entered into this study. Intramuscular injection of human lymphoblastoid interferon (HLBI) at a dose of 3 X 10(6) units was given daily for between 4 and 76 weeks. Treatment with OK-432 then followed HLBI, unless the patient achieved CR or the status of the patient seriously deteriorated during the initial treatment with HLBI. OK-432 was given to 12 patients at a dose of 5KE (Klinische Einheit) 2 days a week for between 10 and 64 weeks. Effectiveness of HLBI therapy was 20% (CR 1 case, MR 3 cases, NC 11 cases, PD 5 cases). With adjuvant OK-432 therapy for patients whose disease proved to be resistant to HLBI, effectiveness was 25% (CR 1 case, MR 2 cases, NC 6 cases, PD 3 cases). The results obtained indicated that OK-432 following IFN is a potentially active antitumor regimen in patients with advanced RCC.

Adult↗
PubMed1985

Effect of age on the hepatic clearance of propranolol in rats.

The effect of age on hepatic clearance of propranolol was investigated in male Wistar rats (3 to 104 weeks old). Pharmacokinetic analysis of the plasma propranolol data obtained after i.v. dosage (1.0 mg kg-1) indicated that both the elimination rate constant and the volume of distribution decreased with age between weeks 5 and 11, after when the distribution volume remained almost constant. The elimination rate constant was reduced consistently with age after 15 weeks. Total body clearance of the drug was reduced extensively with age between weeks 5 and 11 (94 to 43 ml min-1 kg-1) and decreased gradually thereafter. The plasma free fraction of propranolol also decreased with age, falling from more than 20% in 3 to 5 weeks-old rats to about 10% in rats of 52 to 104 weeks. In immature rats the renal clearance was approximately 5 to 12% of the total body clearance. Intrinsic hepatic clearance for unbound propranolol also decreased with age between weeks 7 and 24. As expected from the evidence that propranolol has a high extraction ratio, the extent of its hepatic clearance was significantly dependent on the liver blood flow. These data suggest that the age-dependent decrease in hepatic clearance of propranolol is largely due to a reduction of the elimination rate that might be accompanied by the age-dependent decrease in liver blood flow.

Administration, Oral↗
PubMed1985

Reduced hepatic clearance of propranolol induced by chronic carbon tetrachloride treatment in rats.

Effect of liver injury induced by chronic treatment with carbon tetrachloride for 1 to 4 months on hepatic clearance of propranolol was investigated in male Wistar rats. Plasma propranolol level after i.v. and p.o. dosing (1.0 mg/kg) was always higher in the rats which were treated for 2 and 4 months than in control (sham-injected) rats. The chronic treatment reduced hepatic clearance of propranolol significantly, yielding only approximately 30 to 50% of the control clearance value. Distribution volume of this drug was also significantly reduced by the chronic treatment but seemed to be less sensitive to the treatment than the hepatic clearance. Accordingly, the elimination rate constant was decreased slightly in the rats treated longer than 2 months. The chronic treatment for 2 and 4 months also reduced intrinsic hepatic clearance substantially. The hepatic clearance estimated for both these control and chronically treated rats was significantly dependent on the liver blood flow. Furthermore, propranolol was eliminated much more slowly in the injured liver of the rat which was treated for 2 or 4 months than in the control liver when perfused in in vitro technique. It is, therefore, suggested that the metabolic dysfunction induced by chronic treatment with carbon tetrachloride may be directly related to substantial changes in anatomical arrangement of the hepatic circulation (portasystemic shunting), which may be due to a fibrosis of the tissue.

Animals↗