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Biomedical subjects

S Akazawa

Publications and source records attributed to S Akazawa.

At least 163 records · Page 9Linked to original sources
PubMed1985

Fuel-mediated teratogenesis. Use of D-mannose to modify organogenesis in the rat embryo in vivo.

The unique embryotoxic properties of D-mannose have been used as the basis for a new technique to secure precise temporal correlations between metabolic perturbations during organogenesis and subsequent dysmorphogenesis. Conscious, pregnant rats were infused with D-mannose or equimolar amounts of D-glucose by "square wave" delivery during the interval in which the neural plate is established and early fusion of neural folds takes place, that is, days 9.5-10.0 of gestation. Infusions of mannose to maternal plasma levels of 150-200 mg/dl did not elicit any toxicity in the mothers: motor activity, eating behavior, and serum components (electrolytes, osmolality, bilirubin) did not differ in glucose- vis-à-vis mannose-infused dams. Embryos were excised by hysterotomy on day 11.6 for evaluation of development. Examination with a dissecting microscope did not disclose developmental abnormalities in any of the 136 embryos from glucose-infused mothers or in 62 additional embryos from mothers that had not received any infusions. By contrast, dysmorphic changes were seen in 17 of 191 embryos (8.9%) from mannose-infused mothers. 14 of the 17 had abnormal brain or neural tube development with incomplete neural tube closure in 9 instances. Abnormal axial rotation was present in 8 of the 191 embryos (4.2%) and lesions of the heart or optic vesicles were seen in 4 (2.1%) and 3 (1.6%), respectively. Embryos from mannose-infused mothers displayed significant retardations in somite number, crown-rump length, and total protein and DNA content. These stigmata of growth retardation were more marked in the 17 dysmorphic embryos. The experiments indicate that D-mannose may be employed in model systems with rodents for precisely timed interruptions of organogenesis in vivo. Initial applications are consistent with our earlier suggestion that multiple dysmorphic changes may supervene after interference with communally observed metabolic dependencies during organogenesis. The studies do not identify the vulnerable site(s) within the conceptus (e.g., investing membranes, embryos, or both). However, the findings suggest that dysmorphic events are manifest most markedly in a general setting of embryo growth retardation.

Abnormalities, Drug-Induced↗
PubMed1985

Radioimmunoassay of human plasma apolipoprotein A-1: pretreatment of plasma with guanidine hydrochloride.

A sensitive and specific double antibody radioimmunoassay for apolipoprotein A-1 was first reported by Schonfeld and Pfleger (1). Their procedure required delipidation of the serum since direct radioimmunoassay of apolipoprotein A-1 in untreated sera resulted in much lower values than those obtained from the corresponding delipidated samples. In an attempt to find a rapid and simple procedure for radioimmunoassay of apolipoprotein A-1 without using organic solvents, the serum was subjected to various physical and chemical treatments which disrupt or alter high density lipoproteins (HDL). Heating at 52 C for 3 h and the treatments with 0.1% Triton X-100, 0.05 M sodium dodecyl sulfate (SDS), and 8 M urea resulted in an increased immunoreactivity of apolipoprotein A-1; the reactivity, however, was much lower than that obtained from delipidated samples. Treatment with 6 M guanidine hydrochloride for 3 h at 37 C prior to radioimmunoassay resulted in a maximal increase of apolipoprotein A-1 immunoreactivity comparable to that obtained with delipidated samples. This pretreatment permits a large number of samples to be assayed with complete recovery of apolipoprotein A-1.

Apolipoprotein A-I↗
PubMed1985

[Therapeutic effect of sequential doses of methotrexate (MTX) and 5-fluorouracil (5-FU) in advanced gastric cancer: comparison of intermediate-dose MTX with high-dose MTX].

Twenty-one patients were treated with sequential doses of MTX and 5-FU so as to be classified by MTX dosage into an intermediate MTX-dose group and a high MTX-dose group. In the intermediate-dose MTX group, the drug was given at a dosage of 100 mg/m2 intravenously (i.v.) and followed 1 hour later by 5-FU at 800 mg/m2 i.v. (dripping for 1 hour); the drugs were recycled every 1 week. In the high-dose MTX group, the drug was administered at a dose of 1.5 g/m2 i.v. (dripping for 2 hours) and followed 1 hour later by 5-FU at 1.5 g/m2 i.v. (dripping for 2 hours); the drugs were recycled every 2-3 weeks. Average MTX concentrations in serum at the start of 5-FU administration were 1.69 X 10(-5) and 1.33 X 10(-4) mol/l/h in the intermediate and high-dose MTX groups, respectively. Six (50%) of 12 patients adequately treated with intermediate-dose MTX had a partial response (PR), and one (14.3%) of 7 evaluable patients treated with high-dose MTX had a PR. Major toxicity included diarrhea (33.3%) in the intermediate-dose MTX group and hair loss (71.4%) in the high-dose MTX group. Hematological toxicity was mild in MTX group: six (50%) of 12 patients had a granulocyte count nadir less than 1,000/microliters and one (8.3%) of 12 patients had a platelet count nadir less than 10(5)/microliters in the intermediate-dose MTX group. Five (71.4%) of 7 patients had a granulocyte nadir less than 1,000/microliters and two (28.6%) of 7 patients had a platelet count nadir less than 10(5)/microliters in the high-dose MTX group.

Adult↗
PubMed1985

[Diagnostic values of serum type III procollagen N-terminal peptide in type IV gastric cancer].

Since increased synthesis of collagen has been demonstrated in tissue of type IV gastric cancer, we attempted to distinguish type IV gastric cancer from other cancers by measuring serum levels of type III procollagen N-terminal peptide (type III-N-peptide). Mean serum levels in type IV gastric cancer patients without metastasis were found to be elevated above normal values and developed a tendency to be higher than those in types I, II and III gastric cancer patients without metastasis. Highly positive ratios were found in patients with liver diseases including hepatoma and colon cancer, biliary tract cancer, and esophageal cancer patients with liver, lung or bone metastasis, but only 2 out of 14 of these cancer patients without such metastasis showed positive serum levels of type III-N-peptide. Positive cases in patients with type IV gastric cancer were obtained not only in the group with clinical stage IV but also in the groups with clinical stages II and III. In addition, high serum levels of type III-N-peptide in patients with type IV gastric cancer were seen not only in the cases with liver, lung or bone metastasis but also in cases with disseminated peritoneal metastasis alone. These results suggest that if the serum level of type III-N-peptide is elevated above normal values, type IV gastric cancer should be suspected after ruling out liver diseases, myelofibrosis and liver, lung or bone metastasis.

Carcinoembryonic Antigen↗
PubMed1984

The honeybee syndrome - implications of the teratogenicity of mannose in rat-embryo culture.

Lethal effects of D-mannose in the honeybee have been recognized for more than a half a century. We observed another toxic effect of D- mannose during culture of rat embryos from the early head-fold stage to the 26-to-29-somite stage (Days 9-1/2 through 11-1 of gestation). The addition to culture mediums of 1.5 mg of D-mannose per milliliter caused growth retardation and faulty neural-tube closure in approximately two thirds of the embryos. Mannose effects occurred during the first 24 hours of culture and were attended by modes inhibition of the glycolysis that constitutes the principal energy pathway at this stage of development. Adding more glucose to preserve glycolytic flux or increasing atmospheric oxygen to promote oxidative metabolism offset the mannose teratogenesis. Our findings highlight the metabolic vulnerabilities that exist during early organogenesis, before oxidative flexibility is established. They may serve as a model to explain the teratogenicity of many other seemingly unrelated agents that could act by perturbing glycolysis at this vulnerable stage.

Abnormalities, Drug-Induced↗
PubMed1984

[Clinical trial on the effect of tegafur (SF-SP)].

SF-SP capsules containing sustained release granules of tegafur were orally administered 800 mg, b.i. d. for more than 4 weeks in 20 cases of advanced cancer, 11 of whom were evaluable (stomach 7, colon 1, liver 1, bile 1 and pancreas 1). The evaluation of antitumor effects was based on criteria of the Japan Society for Cancer Therapy, which are are almost the same as those of WHO. One partial remission out of 7 cases of stomach cancer was obtained, and its duration was 40 weeks. Toxicities were anorexia, nausea and vomiting, diarrhea and stomatitis, one case each of anorexia, and nausea and vomiting occurred within 10 days after SF-SP administration. No bone marrow depression, hepatic and renal disorders occurred after long-term SF-SP administration. SF-SP seems to be useful in the treatment of patients with gastric cancer.

Adenocarcinoma↗
PubMed1984

[Combination chemotherapy of CIS-diamminedichloroplatinum (II) and fluoropyrimidine derivatives for advanced gastric cancer: a preliminary report].

A total of thirteen patients with histologically-proved adenocarcinoma of stomach took part in this study at Saitama Cancer Center between July 1982 and September 1983; nine patients were considered evaluable. There were 7 male and 2 female patients with a median age of 52 yrs (range 42-75) and a median performance status of 3 (range 2-4). Patients were treated with a two drug combination of cis-diammine dichloroplatinum (II) and fluoropyrimidine derivatives (tegafur, cormobur ). Three out of 9 evaluable patients (33.3%) had a partial response which lasted 10 months. 6+ months, and 5+ months, respectively. The major toxic effect was a gastrointestinal symptom which was generally manageable. Myelosuppression was mild.

Adenocarcinoma↗
PubMed1984

[Combination chemotherapy of nicardipine and vindesine sulfate, cis-diammine dichloroplatinum (II) for patients with advanced esophageal carcinoma].

Since calcium (Ca) antagonist enhances the antitumor effect of vinca alkaloid in vitro, The authors attempted to combine nicardipine (Ca antagonist) with vindesine sulfate (VDS) and cis-diammine dichloroplatinum (II)(CDDP) for treatment of two patients with advanced esophageal carcinoma who were considered to be resistant to two courses of combination chemotherapy of VDS and CDDP. In the first case nicardipine was given orally and for only one day at a dose of 60 mg followed by 40 mg two and a half hours later. Thirty minutes after 60 mg of nicardipine, 3 mg of VDS on day 1, and 50 mg of CDDP (repeated for 3 days) were given. The maximum plasma concentration of nicardipine was 834.0 mg/ml, and the patient showed a partial response. In the second case nicardipine was given intravenously at a dose of 10 mg/body/hour for 8 hours which was repeated for 3 days. The same dose of VDS and CDDP as the first case was started the second day. The maximum concentration of nicardipine was 254.3 ng/ml, and this patient did not show any response. These results may suggest that a sufficient plasma concentration of nicardipine would obtained some response even in solid tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

[Effect of cis-diammine dichloroplatinum, vindesine sulfate combination chemotherapy for advanced esophageal carcinoma].

Eleven patients with advanced squamous cell carcinoma of the esophagus were treated with a two-drug combination of cis-diammine dichloroplatinum and vindesine sulfate at Saitama Cancer Center between July 1982 and September 1983. Median age was 71 years old (range: 47-48) and 8 patients were greater than 70 years old. Median performance status was 3 (range: 1-4) by Koyama -Saito Criteria. Male female ratio was 6:5. Of the 11 patents, three obtained partial response (27.3%), lasting 8 weeks, 20 weeks+, and 42 weeks-, respectively, and three patients had minor response (27.3%). The major toxic effects including myelosuppression, nausea and vomiting were in general manageable.

Aged↗
PubMed1984

[Diagnostic values of type III Procollagen N-terminal peptide and combination assay of type III procollagen N-terminal peptide with CEA and CA 19-9 in gastric cancer].

It is known that interstitial collagens are initially synthesized as precursors (procollagen), which possess extra peptide segments at both ends of the molecules. The authors attempted to detect the aminoterminal peptide of type III procollagen (type III-N-peptide) and also to measure the carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) together in sera of patients with gastric cancer. The results showed that: (1) mean serum levels and positive ratios of the type III-N-peptide increased as the clinical stage of the patients with gastric cancer advanced; (2) serum levels of the type III-N-peptide were not correlated either with those of CEA or CA 19-9; (3) positive ratios of type III-N-peptide, CEA and CA 19-9 were 51.7%, 44.8% and 48.3%, respectively: (4) positive ratio in combination of the type III-N-peptide with CEA was 69.3% and that in combination of the type III-N-peptide with CEA and CA 19-9 was 72.4%. These results suggest that type III-N-peptide is available for diagnosis of gastric cancer and, that the combination assay of type III-N-peptide with CEA and CA 19-9 is more effective than a single assay for diagnosis.

Antigens, Neoplasm↗
PubMed1983

A highly sensitive enzyme immunoassay for mouse beta nerve growth factor.

A sensitive two-site enzyme immunoassay system for mouse beta nerve growth factor (NGF) was developed, based on the sandwiching of the antigen between anti-mouse beta NGF antibody IgG coated to a polystyrene tube and anti-mouse beta NGF antibody Fab'-linked beta-D-galactosidase (beta-D-galactoside hydrolase, EC 3.2.1.23). This method has the following advantages: (a) the procedures are simple and rapid compared to bioassay or two-site radioimmunoassay; (b) antibody Fab'-beta-D-galactosidase complex is more stable than 125I-labeled antibody; (c) purified beta NGF is detectable at a concentration as low as 10 pg/ml. Our enzyme immunoassay was used to examine the levels of NGF in some tissues of mice. The submaxillary gland contained a high concentration of NGF. However, other tissues, such as the heart, brain, and skeletal muscle, and serum did not contain detectable NGF. These results support recent findings by other investigators that NGF was not found in the organs/tissues other than the submaxillary gland of mice.

Animals↗