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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 883 records · Page 49Linked to original sources
PubMed1985

[Cyclic AMP- and ATP-mediated stimulation of DNA synthesis following partial hepatectomy by prostaglandin-E1 in D-galactosamine injured liver].

D-galactosamine (D-gal) damaged rats were infused with Prostaglandin E1 (PGE1) through a peripheral vein for 40 min. before and after partial hepatectomy. DNA synthesis following 68% partial hepatectomy was severely inhibited by the pretreatment of D-galactosamine. PGE1 infusion (0.5, 1.0 microgram/kg/min) enhanced the DNA synthesis inhibited by D-gal 600 mg/kg significantly (p less than 0.01). After 20 min. of PGE1 infusion cyclic AMP levels of liver tissue was increased as compared with saline infusion in D-gal (600 mg/kg)-damaged rat (p less than 0.05). Also 20 min. and 3 hour after partial hepatectomy. ATP levels of liver tissue was enhanced in PGE1 treated group (p less than 0.05). However the doses of PGE1 infused in this investigation could not increase the hepatic tissue blood flow measured by hydrogen gas clearance method. These results suggest that PGE1 enhance DNA synthesis of injured liver after partial hepatectomy by the mechanism which PGE1 stimulate cyclic AMP production and increase ATP level in hepatic tissue.

Adenosine Triphosphate↗
PubMed1985

Suppressor T lymphocyte induction by a factor released from cultured blastocysts.

For the analysis of immunologic escape mechanisms of embryos during the implantation period in mice, the effects of culture supernatant of blastocysts on in vitro responsiveness to alloantigen of mice was investigated. Blastocyst-cultured conditioned medium was prepared by culturing late blastocysts of outbred ICR mice for 5 days. The addition of culture supernatant containing four or eight blastocysts to allogeneic mixed lymphocyte culture inhibited both the MLR responses and the generation of cytotoxic T lymphocytes (CTL). Preincubation of the culture supernatant with lymphocytes syngeneic to the responder cells of MLR induced potent suppressor cell activity in the MLR. The supernatant did not inhibit the activity of CTL at the effector phase, but preinduced suppressor cells obtained by incubation of splenocytes with the supernatant showed almost complete suppression of CTL activity at the effector phase. Both of the suppressor cells, active on MLR and at the generation phase of CTL as well as active at the effector phase, had a surface phenotype of Thy-1+ and Ig-. The suppressive material could be extracted from the eight-cell stage of fertilized ova or blastocysts but not from unfertilized ova, indicating that the production of the factor(s) is dependent on the stages of early embryogenesis. These results suggest that the active induction of suppressor T lymphocytes by the factor(s) released from implanted embryos is one of the protective mechanisms from maternal immunologic attack.

Animals↗
PubMed1985

Antitumor activity of a new fluoropyrimidine derivative, 5'-deoxy-5-fluorouridine, against murine and human experimental tumors.

5'-Deoxy-5-fluorouridine (5'-DFUR) was evaluated for antitumor activity against four murine tumors (L1210 leukemia, P388 leukemia, Lewis lung carcinoma, and B16 melanoma) and a human mammary carcinoma (MX-1) xenografted in athymic mice. Intraperitoneal administration of 5'-DFUR was ineffective against B16 melanoma implanted intraperitoneally and showed less marked antitumor activity against P388 and L1210 leukemias implanted intraperitoneally or intravenously as compared with that of 5-fluorouracil (5-FU) or 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), while oral administration of 5'-DFUR showed a similar or superior antitumor activity to that of 5-FU or FT-207 against L1210 leukemia implanted subcutaneously. 5'-DFUR showed a marked antitumor activity against MX-1 implanted subcutaneously and also showed slight antitumor activity against Lewis lung carcinoma implanted subcutaneously, while 5-FU and FT-207 did not show any significant antitumor activity against these tumors. These results suggest that 5'-DFUR may be worthy of clinical trial against solid tumors, especially cancers of the breast.

Animals↗
PubMed1985

[Relief of experimental cerebral vasospasm by the intrathecal administration of a calcium antagonist (diltiazem)--in comparison with intra-arterial administration].

The effect of an intra-arterial administration of diltiazem on experimental cerebral vasospasm was previously reported by us. In the present study, the effect of diltiazem on cerebral vasospasm, intracranial pressure and systemic blood pressure were investigated using dogs. Cerebral vasospasm was induced by an injection of 5 ml of autologous blood into the cisterna magna. Diltiazem (10(-6) M) was administrated into the cisterna magna and the dilating effect of the drug on the basilar artery was monitored angiographically. The intrathecal administration of diltiazem relieved the vasospasm for more than 30 minutes, same as that of the intra-arterial administration. However, the intracranial and blood pressures remained unchanged. The changes of concentration of the drug in CSF and plasma following the intracisternal administration of 14C-diltiazem were measured using rabbits. The concentration of an administered diltiazem in CSF and plasma was quickly decreased and reduced to 2% of its initial value after one hour (t1/2 = 8 min). Our results show that even the concentration of diltiazem is very low in CSF, the vasodilating effect continues for more than 30 min. This suggests that the intrathecal administration of diltiazem may be useful for the prevention and treatment of the cerebral vasospasm following subarachnoid hemorrhage.

Animals↗
PubMed1985

[Clinical review and antibacterial effect of aztreonam in infections in obstetrics and gynecology].

Clinical effect in obstetrics and gynecology was studied on aztreonam (AZT), a potent monobactam antibiotic for Gram-negative bacteria. AZT was tested for 7 cases and effective for all of them with quite a high effective rate of 100%. Neither side effect nor abnormal laboratory findings were noted and it sufficiently proves the property of AZT, a totally chemical-synthesized product with lower incidence of allergic reaction. The above results suggest that AZT is useful for obstetrics and gynecologic infections in view of its high stability to beta-lactamase and dehydropeptidase and high potency against Gram-negative bacteria.

Adult↗
PubMed1985

Albumin microspheres as drug carriers.

In order to improve the therapeutic index in cancer chemotherapy, it is necessary to deliver antitumor agents to target sites (tumor sites). One of the methods used to deliver those agents to target sites is to employ nontoxic and biodegradable drug carriers. Considerable efforts have been directed toward the development of drug carriers, i.e., DNA complexes, protein-drug conjugates, lactic/glycolic acid polymer, liposomes, emulsion, etc. Albumin microsphere is one of those drug carriers. This review describes the progress which has been made during the last 10 to 15 years in the application of albumin microspheres as drug carriers to cancer chemotherapy. It will cover a wide range of subjects including the preparation and physicochemical properties of microspheres containing antitumor agents, pharmacokinetics of the microspheres in experimental animals, and the antitumor efficacy by intra-arterial use against human primary metastatic liver tumor.

Albumins↗
PubMed1985

[Preoperative cancer chemotherapy for gastric cancer].

Preoperative cancer chemotherapy for gastric cancer was reviewed with special emphasis on histologic findings and survival. Preoperative chemotherapy with intravenous, split administration of MMC 40 mg caused considerable damage to "micro-solitary metastatic foci" in metastatic lymph nodes. In view of the lipid-adsorbing ability of the lymphatic stream, emulsified 5-FU was used orally in 182 patients with gastric cancer; histologic findings revealed that the emulsified 5-FU enhanced the antitumor efficacy for metastatic lymph nodes as well as the primary lesion. However, the 5-year survival rate for gastric cancer patients undergoing preoperative emulsified 5-FU therapy did not differ from the control, with only the exception of patients with Stage III gastric cancer. On the other hand, combined therapy involving preoperative intra-arterial infusion and surgery was carried out in 62 patients with gastric cancer. These preoperative treatments using MMC, 5-FU, VLB, MTX and/or cytosine arabinoside entailed continuous infusion for 15 to 20 hours; the histologic changes observed revealed marked antitumor effects on the primary focus as well as metastatic lymph nodes. The five-year survival rate for the 62 patients was compared with that for 99 patients with gastric cancer in the corresponding period. The survival rate was analyzed based on the degree of serosal invasion. The overall survivals in the 62 patients were higher than those in the controls for the first 3 years. At 4 to 5 years, the survival rates for both the treated and control groups were approximately equal. In patients without serosal invasion, the survival rates were higher in treated cases than in the controls for the first 2 years. Thirty-nine patients with serosal invasion had significantly higher survival rates than the controls for the first 3 years. The survival rates for the treated patients with cancerous infiltration of ther organs were about the same as those for the corresponding control patients.

Administration, Oral↗
PubMed1985

Toxicological study on a new nitrosourea derivative, 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea.

TA-077, 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea, is a new water-soluble nitrosourea derivative which is disubstituted at the N-3 position of the structure, and is activated by a unique mechanism whereby organic isocyanates can never be produced. In order to clarify the biological functions of the organic isocyanates which common nitrosourea derivatives generate, TA-077 was tested in BDF1 mice for lethality, weight loss and hematological toxicity. TA-077 showed qualitatively and quantitatively similar toxicity to other nitrosourea derivatives which generate organic isocyanates, such as 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosour ea (ACNU), methyl 6-[3-(2-chloroethyl)-3-nitrosoureido ]-6-deoxy-alpha-D-glucopyranoside (MCNU), and 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), indicating that the organic isocyanates do not play an important role in the biological activity of the nitrosourea derivatives. Furthermore, the toxicity of TA-077 did not increase significantly (except for weight loss) when the drug was administered daily for five days, and TA-077 given according to this schedule showed far more effective antitumor activity than when given as a single treatment. These results suggested that TA-077 is an analog suitable for consecutive administration in cancer treatment.

Animals↗
PubMed1985

[Multimodality therapy of colorectal cancer].

Multimodality therapy for colorectal cancer is composed of surgery, chemotherapy and irradiation; and hyperthermia joins them recently. As patients with operable colorectal cancer are a good candidate for a chemotherapeutic approach, we began postoperative adjuvant chemotherapy since 1971. On the other hand, our treatment policy towards inoperable cases is various treatments combined with the four therapies described above. The most patients with hepatic metastasis are unamenable for surgery, and they have been mainly treated with intra-arterial chemotherapy. With conventional infusion treatment, however, the infusion drugs are eliminated rapidly from the drainage vein. Thus, we prepared biodegradable albumin microspheres containing MMC (mean diameter 45 +/- 8 micron); and in 6 patients with liver metastasis, we infused MMC microspheres into the proper hepatic artery, with marked tumor regression. Hyperthermia treatment has been performed with ThermaTech 2000 (International Institute for Medical Sciences, U.S.A.), which has a complete capacitive, 3-channel, "crossfire" heating system operating by RF at 13.56 MHz. Six patients with local recurrence and/or hepatic metastasis were treated by hyperthermia combined with chemotherapy or irradiation, with a fair success in tumor response and improvement of subjective symptoms.

Aged↗
PubMed1985

[Effects of cerebral protective agents in experimental cerebral ischemia. Relationship between the degree of ischemia and EEG].

We have previously demonstrated that the preischemic administration of perfluorochemicals (PFC) in combination with 20% mannitol, vitamin E and dexamethasone is effective in protecting the brain from cerebral ischemia. This experimental study was designed to evaluate the effect and limitation of the post-ischemic administration of those 4 agents on cerebral ischemia. We used "Canine model of complete ischemic brain regulated with a perfusion method." Using this model we were able to control the amount of blood flow to the left cerebral hemisphere by using an infusion pump. Infusion blood volume was reduced to 30%, 40% or 50% of the normal state, then the combined treatment was started 1,2,3,4,5 or 6 hours after the onset of ischemia in each ischemic group. By monitoring the EEG for 8 hours of ischemic period, we were able to evaluate the effect of the drugs on cerebral ischemia. In untreated groups, electrical activity deteriorated gradually. In the 30% ischemia group, the EEG became isoelectric within 1 hour following ischemia. In half of the 40% ischemia group, the EEG became isoelectric but in the other half low voltage slow wave were seen to last for 6-8 hours. In the 50% group, the EEG deteriorated gradually but did not disappear within 8 hours. The effectiveness of the treatment was judged by the degree of the recovery of electrical activity. The effectiveness of the treatment appeared to depend on the severity and the duration of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗