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Biomedical subjects

S Akazawa

Publications and source records attributed to S Akazawa.

At least 145 records · Page 8Linked to original sources
PubMed1987

Effects of hypoglycaemia on early embryogenesis in rat embryo organ culture.

As congenital malformations may be caused by perturbations of glycolytic flux on early embryogenesis [16], effects of hypoglycaemia were investigated by using rat embryo organ culture. Nine and one-half day old rat embryos were grown in vitro for 48 h (day 9 1/2 to 11 1/2) in the presence of hypoglycaemic serum for different hours during the culture period. Hypoglycaemic serum was obtained from rats given insulin intraperitoneally. On exposure to hypoglycaemic serum during the first 24 h of culture (day 9 1/2 to 10 1/2), embryos showed marked growth retardation and had increased frequencies of neural lesions (42.7% versus 0%, p less than 0.01), in contrast to hypoglycaemic exposure during the second 24 h of culture (day 10 1/2 to 11 1/2), where only minor growth retardation and low frequencies of neural lesions (2.4% versus 0%, NS) were seen. Even exposure to hypoglycaemic serum for a relatively short period (8 h) during the first 24 h of culture resulted in neural lesions at the frequency of 9.3-13.3%. The embryos exposed to hypoglycaemia demonstrated decreased glucose uptake and lactic acid formation, indicating decreased energy production via glycolysis that constitutes the principal energy pathway at this stage of embryonic development. These results suggest that hypoglycaemia during critical periods of embryogenesis has adverse effects on the development of the embryo and these effects might be mediated through metabolic interruption of embryogenesis.

Animals↗
PubMed1987

[Sequential methotrexate-5-fluorouracil (MTX-5-FU) treatment of patients with advanced gastric and colorectal cancer. Sequential Methotrexate-5-FU Study Group].

A multicenter cooperative study was conducted from July 1984 to March 1986 to evaluate the clinical efficacy of sequential MTX-5-FU treatment in 96 cases of advanced gastric cancer and 39 cases of colorectal cancer. 5-FU 600 mg/m2 i.v. was given and MTX 30 mg/m2 (A), 100 mg/m2 (B) and 300 mg/m2 (C) i.v. were given, and the administration interval between MTX and 5-FU was 1 to 3 h for the gastric cancer group, and 7 h for the colorectal cancer group. Leucovorin rescue of 10 mg/m2 p.o. was given 24 h after MTX administration. In the gastric cancer group, the response rate for Regimen A was 23.2% (CR 1 and PR 12) out of 56 evaluable cases, and for Regimen B, 40.5% (CR 1 and PR 14) out of 37 evaluable cases. In the colorectal cancer group, the response rate for Regimen A was 28.6% (PR 6) out of 21 evaluable cases and for Regimen B, 20.0% (PR 3) out of 15 cases. Median survival time for the gastric cancer group was 5.5 months with Regimen A and 7.6 months with Regimen B, and for the colorectal cancer group 10.9 months with Regimen A and 7.9 months with Regimen B. Main adverse effects were marrow impairment and gastrointestinal symptoms such as nausea, diarrhea, and stomatitis. In this study Regimen B showed relatively good results. In order to evaluate the biochemical modulation occurring with sequential MTX-5-FU treatment, a further phase III study in gastric cancer patients should be conducted.

Adult↗
PubMed1987

[A case of recurrent gastric cancer successfully treated with a combination of cisplatin and carmofur].

A 51-year-old man with recurrent gastric cancer was treated by combined administration of Cisplatin and Carmofur. The target sites were the abdominal lymph nodes and the area of invasion to the stomach. Cisplatin (50 mg/body/day) was given for 3 days, while Carmofur (400-800 mg/body/day) was administered daily in 1 course. After 1 course of administration, the target tumor was reduced in size and the therapy was continued. A complete response was confirmed by upper gastrointestinal roentgenography, endoscopy and echography after 8 courses of Cisplatin administration. The patient has survived for 2 years 6 months in a state of CR. This case suggests that a combination therapy of Cisplatin and Fluoropyrimidine derivatives might be effective for gastric cancer.

Aged↗
PubMed1986

An enzyme-linked immunosorbent assay for antibodies against saline-soluble muscle components in myasthenia gravis.

An enzyme-linked immunosorbent assay (ELISA) system has been developed for measuring antibodies against rat skeletal muscle components solubilized with phosphate-buffered saline. With this assay, 53.8% (50/93) of sera from patients with myasthenia gravis (MG) was positive (the values over the mean plus 3 SD of 256 healthy individuals were considered significant). No sera from patients with neurological disorders other than MG gave positive values (0%; 0/60). No correlation between titers of antibody against the muscle components and those of anti-acetylcholine receptor antibody (r = 0.01) was found. These results indicate that our ELISA system is useful for diagnosing myasthenia gravis.

Autoantibodies↗
PubMed1986

A new method of detection of islet cell antibodies (ICA) using peroxidase-labeled protein A, and incidence of ICA in type 1 (insulin-dependent) diabetes.

We have developed a new method of detecting islet cell antibodies using peroxidase-labeled protein A, and have determined the incidence of ICA in Type 1 (insulin-dependent) diabetes in Japan. In our method, fresh frozen sections of human pancreas and serum samples were incubated and then treated with peroxidase-labeled protein A at room temperature. Conjugates of peroxidase and protein A were subjected to Sephadex G-200 column chromatography, and only the 80,000 dalton peak was employed. The treated sections were allowed to react with haematoxylin and eosin (HE) to confirm the localization of islet cells. With this method, human pancreatic tissues can be used regardless of age and blood type, and the stained sections can be stored for more than 5 years. Serum samples obtained from 52 patients with Type 1 diabetes, 54 with Type 2 (non-insulin-dependent) diabetes and 100 control subjects were examined. In patients with Type 1 diabetes, islet cell antibodies were detected in 14 of 14 (0.5 years after onset), 3 of 6 (0.5-1 years after onset), 7 of 16 (1-5 years after onset) and 2 of 16 (more than 5 years after onset). In contrast, only 4 of 54 patients with Type 2 diabetes and none of the controls were ICA positive. It is concluded that, with our newly developed method using peroxidase-labeled protein A, ICA is present in all Japanese Type 1 diabetic patients whose diabetic manifestations are less than 0.5 years duration from onset.

Adult↗
PubMed1986

Mitogenic heparin-binding lectin-like protein from cloned thymic myoid cells.

A mitogenic heparin-binding (reactive) lectin-like protein (HBP) was purified from the extract of a cloned rat thymic myoid cell R615B2 by a one-step procedure of affinity chromatography on a heparin--Sepharose CL-6B column. Four distinct peptide bands with molecular weights of 10,000, 13,000, 13,700, and 14,600 were detected on SDS-polyacrylamide gel electrophoresis. This protein is mitogenic at concentrations of as low as 1.1-70.0 ng/ml for peanut lectin-nonagglutinated thymocytes and splenocytes from euthymic mice and rats but not for splenocytes from nude mice. These results indicate that thymic myoid cell-derived HBP is an important signal for one particular step in T-cell differentiation.

Animals↗
PubMed1986

The 1986 McCollum award lecture. Fuel-mediated teratogenesis during early organogenesis: the effects of increased concentrations of glucose, ketones, or somatomedin inhibitor during rat embryo culture.

Whole rat embryos were explanted at head-fold, late pre-somite stage (day 9.5 of gestation) and cultured in rat sera varyingly supplemented with glucose (3, 6, 9, or 12 mg/mL), D,L sodium beta-hydroxybutyrate (2, 4, 8, or 16 mM), or both (6 mg/mL D-glucose plus 8 mM beta-hydroxybutyrate). During 48 h culture, increasing glucose alone or beta-hydroxybutyrate alone effected growth retardation and faulty neural and extraneural organogenesis in dose-dependent fashion. Synergistic dysmorphogenic effects occurred when minimally teratogenic concentrations of glucose and beta-hydroxybutyrate were combined. Sera from diabetic animals containing somatomedin inhibitor bioactivity were also able to produce growth retardation and major developmental lesions in presence of amounts of glucose and ketones which of themselves were not teratogenic. Thus, aberrant fuels and fuel-related products can impair growth and organogenesis in early post-implantation embryo. Such fuel-mediated teratogenesis may be multifactorial and include possibilities for synergistic and additive interactions.

3-Hydroxybutyric Acid↗
PubMed1986

Relationships between glucose and mannose during late gestation in normal pregnancy and pregnancy complicated by diabetes mellitus: concurrent concentrations in maternal plasma and amniotic fluid.

Enzymatic assays were modified to permit sensitive and highly reproducible simultaneous measurements of D-mannose and D-glucose in biological fluids during weeks 34-40 of human pregnancy. Plasma mannose and glucose averaged 9.8 +/- 0.4 (+/- SEM) and 790 +/- 16 micrograms/ml, respectively, after an overnight fast in pregnant women (n = 22) with normal carbohydrate metabolism. Significantly higher plasma mannose levels were found, despite only minor increases in plasma glucose, in pregnant women with relatively well controlled diabetes mellitus after an overnight fast (16.9 +/- 0.6 micrograms/ml mannose; 883 +/- 29 micrograms/ml glucose; n = 31) or 3-4 h after breakfast (15.7 +/- 1.2 micrograms/ml mannose; 1159 +/- 101 micrograms/ml glucose; n = 19). Plasma mannose correlated significantly with plasma glucose in the women with diabetes mellitus, particularly after an overnight fast. Samples of amniotic fluid were also obtained from the gravida with diabetes mellitus to provide some index of simultaneous relationships in utero. Amniotic fluid mannose and glucose averaged 5.9 +/- 0.4 and 302 +/- 24 micrograms/ml, respectively, after an overnight fast and 6.7 +/- 1.3 and 459 +/- 84 micrograms/ml 3-4 h after breakfast. In amniotic fluid, as in plasma, the concurrent levels of mannose and glucose conformed to relatively fixed relationships. Thus, both fetus and mother appear to be exposed to readily demonstrable amounts of mannose during late gestation and the absolute as well as relative abundance of mannose may be increased coincident with faulty maternal glucoregulation. However, since mannose did not exceed 3% of the concurrent concentration of glucose in any instance, it does not seem likely that endogenous levels of circulating mannose can modify glucose utilization appreciably by competing with glucose for phosphorylation via hexokinase and subsequent intracellular processing.

Adolescent↗
PubMed1986

The cytotoxicity of 5-fluorouracil is due to its incorporation into RNA not its inhibition of thymidylate synthase as evidenced by the use of a mouse cell mutant deficient in thymidylate synthase.

The biochemical basis for the cytotoxicity of 5-fluorouracil is still controversial; it is not clear whether the mechanism involves interference with DNA metabolism or incorporation of the drug into RNA. To distinguish between these two possibilities, we took advantage of a mutant strain of the mouse mammary tumor cell line FM3A that is deficient in thymidylate synthase, which is widely believed to be the target of 5-fluorouracil. We demonstrated that the target of the cytotoxicity of 5-fluorouracil was not thymidylate synthase; instead, the cytotoxicity was positively correlated with drug incorporation into RNA under conditions where thymidine increased the incorporation of 5-fluorouracil into RNA concentration-dependently.

Animals↗
PubMed1986

[Biochemical modulation of 5-FU by thymidine and N-phosphoacetyl-L-aspartate: the relation between 5-FU incorporation into RNA and its cytocidal effect].

We attempted to study the relation between 5-FU incorporation into RNA or DNA and the cytocidal effect of 5-FU using thymidine (TdR) and the effect of N-phosphoacetyl-L-aspartate (PALA) on the cytotoxicity of 5-FU. A mouse mammary carcinoma cell line FM3A was used in all of the experiments. The results showed that: addition of TdR to cell cultures resulted in an increase of 5-FU incorporation into RNA and although 5-FU incorporation into nucleic acid decreased, addition of 10(-3) M TdR induced of complete incorporation of 5-FU into only RNA as revealed by alkaline hydrolysis and cesium gradient analysis; no addition of TdR caused 5-FU to be completely incorporated into DNA only; cytocidal effect of 5-FU, in a clonogenic assay, occurred only during the time when TdR was added to the cell culture; PALA possessed the capacity to enhance the cytocidal effect of 5-FU in a clonogenic assay. These results confirmed that 5-FU incorporation into RNA is necessary for the cytocidal effect of 5-FU and that both TdR and PALA are available as 5-FU-modulating agents for enhancement of the cytocidal effect.

Animals↗