Biomedical subjects

D Nakae

Publications and source records attributed to D Nakae.

77 records · Page 5Linked to original sources

PubMed1984

Distribution and metabolism of N-nitrosobis(2-hydroxypropyl)amine in rats.

The metabolic fate of the lung carcinogen N-nitrosobis(2-hydroxypropyl)amine (ND2HPA) in male Wistar rats was studied. The blood level after a single intraperitoneal (i.p.) injection of [1-14C]-ND2HPA at a dose of 3 g/kg body weight reached a maximum within 1 h. Most of the administered 14C was eliminated via the urine; 90.8% of the 14C was excreted in urine within 24 h, 5.5% in faeces, and 3.2% in expired air. About 11% of the 14C was detected in bile collected over 24 h. A relatively high concentration of 14C was found in the blood and target organs, such as the lung, liver, thyroid gland and kidney 1 h after treatment. Analysis by high-pressure liquid chromatography showed that the 14C in the blood and urine was mostly accounted for by unchanged ND2HPA, together with smaller amounts of N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (N2HP2OPA). ND2HPA and N2HP2OPA were also detected in the lung and liver of rats 30 min to 12 h after the administration and were present in higher concentrations in the blood and lung than in the liver and pancreas. Besides ND2HPA and N2HP2OPA. N-nitrosomethyl(2-hydroxypropyl)amine (NM2HPA) was also found in urine collected over 6 h. ND2HPA, N2HP2OPA and NM2HPA showed mutagenicity in the Salmonella assay system with metabolic activation by a 9000 X g supernatant of rat liver, and N2HP2OPA was also mutagenic in the presence of a rat lung preparation. These data suggest that N2HP2OPA and NM2HPA might be important intermediates in the metabolic activation of ND2HPA to its ultimate carcinogenic form in rats.

Animals↗

PubMed1983

Possible role of poly(ADP-ribose) polymerase on the early stage of liver carcinogenesis by diethylnitrosamine in rats.

In the present experiments, we studied the effect of poly(ADP-ribose) polymerase inhibitors on the early stage of liver carcinogenesis by diethylnitrosamine (DEN) in rat liver in order to clarify the biological role of this enzyme in cancer induction. We used 3-aminobenzamide(ABA), 5-methylnicotinamide(MNam), and thymidine as the inhibitors and measured the numbers and sizes of gamma-glutamyltranspeptidase (gamma-GTP) positive foci as a marker of initiated cell populations. When ABA was given within 4 hr after DEN treatment, it had almost the same effect as a partial hepatectomy and caused dose-dependent enhancement of the induction of gamma-GTP positive foci. The administration of ABA at a dose of 600 mg/kg was effective to enhance the induction of the foci 1 day before to 1 day after 20 mg/kg DEN initiation. The enhancing effect of MNam and thymidine at a dose of 600 mg/kg was observed to the same extent as that of ABA. Based on these results the experiments were extended to the mechanisms of the enhancing effect of ABA. Liver cell necrosis was not detected by measuring serum GOT and GPT levels and histology after DEN and ABA administration. Further, the initiating and promoting activities of ABA in liver carcinogenesis were studied and ABA per se was not found to take part in either activity. These results indicate that poly(ADP-ribose) polymerase plays an important role in the early stage of liver carcinogenesis by DEN and provides a new avenue for studying the mechanisms of the initiation process in chemical carcinogenesis.

Alanine Transaminase↗

PubMedDate not supplied

Clinical characteristics and proliferating activity of intrahepatic cholangiocarcinoma.

To assist in the development of new approach to the palliation and treatment of intrahepatic cholangiocarcinomas, we classified tumours into mass-forming (MF), peri-ductal extension (PD), and spicula-forming (SF) types in 14 subjects who underwent surgical treatment. Lymph node metastasis and microscopic lymphatic invasion were pronounced in the PD and SF types. Furthermore, in SF type tumours the incidence of microscopic vascular and perineural invasion was high. The proliferating cell nuclear antigen labelling index, a reflection of the proliferation rate of tumour cells, was significantly higher in PD and SF types than in the MF type. The prognosis associated with the MF type tended to be better than that of the other two types. For the MF type, liver resection with tumour free margins must be performed, whereas for the PD and SF types, aggressive treatment, that is a combination of extensive liver resection, lymph node dissection, and effective adjuvant anti-cancer therapy should be provided to aim at life-long cure.

Adult↗

PubMedDate not supplied

Comparative changes in the liver of female Fischer-344 rats after short-term feeding of a semipurified or a semisynthetic L-amino acid-defined choline-deficient diet.

Groups of female Fischer-344 rats were fed a semipurified choline-deficient (CD) diet, or a semisynthetic L-amino acid-defined choline-deficient (CDAA) diet, for up to 12 wk and effects of the 2 diets on the liver were compared. Steatosis was diffuse and more severe throughout in rats fed the CDAA diet than in rats fed the CD diet. Greater elevations in serum aspartate and alanine aminotransferase activities were also present in the former rats, along with higher 2-bromodeoxyuridine labeling indices in the liver. Discrete amounts of 8-hydroxyguanine were detected in liver DNA, but were not significantly different in rats fed the 2 diets, or from those present in a group of control rats killed at 0 time. Glutathione S- transferase placental form-positive focal lesions were not observed in any of the rats. The results show that the CDAA diet causes more severe degrees of steatosis and liver cell death and proliferation than the CD diet, raising the possibility that it may, in contrast to the CD diet, result in the eventual induction of hepatocellular carcinomas in female Fischer-344 rats.

Alanine Transaminase↗

PubMedDate not supplied

Protection against lipid peroxidation induced during preservation of lungs for transplantation.

The questions of whether oxygen-derived free radicals are induced during preservation of lungs and, if so, how such radicals might relate to reperfusion injury were investigated by means of an isolated canine lung model. Lungs were obtained from 16 mongrel dogs and divided into groups 1 (n = 6), 2 (n = 5), and 3 (n = 5). The lungs of groups 1, 2, and 3 were flushed through the pulmonary artery with Euro-Collins solution alone, the solution with superoxide dismutase (120,000 U/L), and the solution with allopurinol (1 mmol/L), respectively, at 4 degrees C and then stored for 4 hours in the respective solutions at 4 degrees C with clamped bronchi. They were then reperfused for 2 hours by means of an isolated lung model. Lung lipid peroxidation was sequentially determined. The lung functional status was assessed by systolic pulmonary arterial pressure and end-inspiratory airway pressure. The lung edema was assessed by lung wet/dry weight ratio. Lipid peroxidation was induced after 1 hour of preservation and the first 30 minutes of the reperfusion in group 1 and only 2 hours of the reperfusion in group 2, whereas no induction was observed in group 3. Values for systolic pulmonary arterial pressure and end-inspiratory pressure in group 1 were significantly higher than those in group 3 (p < 0.05). The lung wet/dry weight ratio in group 1 was significantly higher than that in groups 2 and 3 (p < 0.05). The present results indicate that the administration of free radical scavengers in the preservation may effectively improve conditions for lung transplantation.

Airway Resistance↗