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Biomedical subjects

S Furusawa

Publications and source records attributed to S Furusawa.

At least 199 records · Page 11Linked to original sources
PubMed1982

I-J restrictions on the activation and interaction of parental and F1-derived TS3 suppressor cells.

An experimental system was developed to independently analyze the H-2 and Igh genetic restrictions at two steps of the 4-hydroxy-3-nitrophenylacetyl hapten (NP) suppressor cell pathway. This experimental system allowed genetic analysis of the activation of TS3 cells by hybridoma-derived TsF2 and independent analysis of the genetic restrictions that controlled the interaction of the TS3 cells with their target population. Thus, TS3 cells were activated in vitro with monoclonal H-2b or H-2k-derived TsF2. The activated TS3 cells were then adoptively transferred to TS3-depleted (cyclophosphamide-treated) recipients of various genotypes. When the TS3-containing lymph node population was activated in vitro for 2 h, suppressive activity was only noted in combinations of TSF2, TS3, and recipients that were matched at both the I-J and Igh gene complexes. The data indicate that TsF2 can activate TS3 cells and that both the activation and the interaction of TS3 cells are I-J and Igh restricted. Using (B10 x B10.BR)F1 mice as TS3 donors, we noted that H-2b-derived TsF2 activated these F1 TS3 cells to suppress NP-specific cutaneous sensitivity responses in H-2b but not in H-2k recipients. Reciprocal experiments using H-2k-derived TsF2 demonstrated that only an H-2k-restricted population was activated in the F1-derived TS3 cells. The simplest explanation to account for these observations is that two distinct populations, each of which is restricted to a parental I-J determinants, exists in the heterozygous F1 TS3 population. Furthermore, we demonstrated that both I-Jb and I-Jk determinants are expressed on F1-derived TS3 cells. These observations are discussed in terms of the mechanisms involved in immunoregulation.

Animals↗
PubMed1982

Drug interaction of antitumor drugs. III. Antitumor activity of tegafur in lipopolysaccharide-treated mice.

The effect of lipopolysaccharide (obtained from Escherichia coli, LPS) on the antitumor activity, acute toxicity and metabolism of tegafur was investigated in mice in comparison with 5-fluorouracil (5-FU). It was found that the intravenous administration of LPS (1.25 or 2.5 mg/kg) 24 hr prior to tegafur decreased the antitumor activity of tegafur against the solid form of Sarcoma 180. On the acute toxicity of tegafur or 5-FU, the lethality of the former was decreased and that of the latter was enhanced by the pretreatment with LPS 24 hr before. In LPS-treated mice, after the administration of tegafur, the level of tegafur in plasma was higher and the elevated level maintained longer than in untreated mice; and a small amount of 5-FU was released. A high level of 5-FU in plasma after the administration of 5-FU was also observed in LPS-treated mice. In the liver and kidneys of LPS-treated mice, the level of 5-FU after the administration of tegafur or 5-FU was higher, and its conversion of 5-FU to fluorouridine (FUR) was lower than that of control mice. On the other hand, LPS inhibited significantly the hepatic drug-metabolizing enzymes 24 hr after. It can, therefore, be presumed that the antitumor activity of tegafur was affected with LPS as a result of inhibition of conversion from tegafur to 5-FU or from 5-FU to FUR mainly according to depression in the hepatic drug-metabolism.

Animals↗
PubMed1982

Effect of doxapram on the action of other drugs and the hepatic drug-metabolizing system in mice.

Effects of doxapram, a respiratory stimulant, on the action of other drugs and the activity of the hepatic drug-metabolizing enzyme were studied in mice. The hypothermic effect induced by aminopyrine and the muscle relaxant effect induced by meprobamate were potentiated by the pretreatment with doxapram 60 min before. Furthermore, doxapram significantly enhanced the lethalities of picrotoxin and strychnine and the analgesic actions of aminopyrine and morphine. The plasma concentration of aminopyrine or pentobarbital in doxapram-treated mice was higher than those in untreated mice, and the plasma concentration of normustard related to an active metabolite of cyclophosphamide after the administration of cyclophosphamide was lower in doxapram-treated mice. On the other hand, doxapram (50 mg/kg, i.p.) reduced remarkably the activities of aminopyrine N-demethylase and aniline hydroxylase in the hepatic 9,000xg supernatant fraction, and also reduced the cytochrome P-450 contents in hepatic microsomes. However, no significant alteration by doxapram was observed on the activities of NADH-ferricyanide reductase and NADPH-cytochrome c reductase and cytochrome b5 contents. It seems likely that the mechanisms of the interaction between doxapram and combined drugs involved the depression of the hepatic drug-metabolizing system in microsomes and a subsequent variation of drug level in the plasma.

Aminopyrine↗
PubMed1981

Analysis of T cell hybridomas. I. Characterization of H-2 and Igh-restricted monoclonal suppressor factors.

Five hybridoma T cell lines were prepared by fusion of second order suppressor T cells (Ts2) with the BW5147 thymoma. The culture supernates from these T cell hybrids contained a factor, TsF2, which specifically suppressed 4-hydroxy-3-nitrophenyl acetyl hapten (NP)-induced cutaneous sensitivity responses. TsF2 activity was observed when the factor was administered during the effector phases of the immune response. TsF2 bears I-J determinants and has binding specificity for NPb idiotypic determinants. TsF2 suppressor activity could be absorbed on antigen-primed H-2-incompatible T cells but cannot suppress H-2-incompatible mice. In addition to this H-2 restriction, which maps to the I-J subregion, monoclonal TsF2 also has an Igh genetic restriction. The present results are combined with previous data to describe the cellular interactions leading to immune suppression.

Absorption↗
PubMed1981

Therapeutic activity of pretazettine on Ehrlich ascites carcinoma: adjuvant effect on standard drugs in ABC regimen.

A narcissus alkaloid, pretazettine hydrochloride (PTZ), has been shown to be active against Ehrlich ascites carcinoma. The Ehrlich cells are more sensitive to PTZ in DBA/2 mice than in Swiss mice. The therapeutic activity of the individual standard drugs in ABC (adriamycin, BCNU, and cyclophosphamide) regimen against Ehrlich ascites carcinoma has been increased remarkably by the adjuvant therapy of PTZ following the preliminary use of standard drugs. The independent inhibitory action of PTZ on cellular protein synthesis in the presence of the DNA-binding agent has been demonstrated in KB-cell cultures. Adriamycin-pretreated KB cells are found to be more sensitive to PTZ than nontreated cells.

Alkaloids↗
PubMed1981

Biphasic effect of doxapram on hypnotic activity of pentobarbital in mice.

The effect of doxapram, a respiratory stimulant, on the pentobarbital sleeping time was investigated in mice. The sleeping time induced by the intraperitoneal injection of pentobarbital was prolonged 0--120 min after the administration of doxapram (25-100 mg/kg, i.p.). The pretreatment with doxapram 60 min before had no effect on the anesthetic time induced by ether and on the sleeping time induced by the intracerebroventricular injection of pentobarbital, while increased the lethality of pentobarbital only slightly and the levels of pentobarbital in the plasma and brain significantly. The activities of pentobarbital oxidase and aminopyrine N-demethylase in the 9000 X g supernatant fraction of the liver were inhibited by the pretreatment with doxapram 60 min before the test. On the other hand, 12-24 hr after the injection of doxapram the pentobarbital sleeping time was markedly shortened. Thus, the biphasic effect of doxapram, prolongation at first and shortening later, on the pentobarbital sleeping time was observed. It is possible that doxapram inhibits the hepatic microsomal drug-metabolizing enzymes without an increase in the sensitivity of the central nervous system at first and stimulates these enzymes during the second phase.

Animals↗
PubMed1981

[Butoctamide enhancement of the antitumor activity of 6-mercaptopurine on Ehrlich solid tumors in mice (author's transl)].

Effects of butoctamide (N-(2-ethylhexyl)-3-hydroxybutyramide, L-2) on the antitumor activity of 6-mercaptopurine (6-MP) against Ehrlich solid tumors in mice were investigated. No change was observed in tumor growth after either oral or intraperitoneal administration of butoctamide (100 mg/kg/day X 7). This drug increased the activity of a low dose of 6-MP (2.5 approximately 10 mg/kg/day. i.p., X 7), but did not change the activity of a high dose of 6-MP (40 approximately 80 mg/kg/day, i.p., X 7). The antitumor activity of thioinosine (6-MP riboside) was similarly increased by administration of butoctamide (100 mg/kg/day, i.p., X 7). On the other hand, concomitant administration of butoctamide with cyclophosphamide, methotrexate, mitomycin C or adriamycin had no effect on the activity of these anticancer drugs. In butoctamide (100 mg/kg/day, i.p., X 7)-treated mice, the antitumor activities of a single administration of 6-MP and cyclophosphamide were not increased. Butoctamide stimulated the hypoxanthine-guanine phosphoribosyltransferase activity and inhibited the xanthine oxidase activity of mouse liver, to a certain degree as compared to controls. Butoctamide may promote conversion from 6 MP to thioinosinic acid monophosphate to a biologically active state, rather than to thiouric acid or hypoxanthine which would be inactive.

Amides↗