Noriyuki Nagahara

Granulocytosis associated with malignant neoplasms: a clinicopathologic study and demonstration of colony-stimulating activity in tumor extracts.

We studied seven cases of malignant neoplasms, taken from various sites in the body, that were associated with marked granulocytosis. The seven cases were characterized clinically by marked granulocytosis with mature neutrophils, nonspecific inflammatory signs, and a rapid and progressive fatal course of the disease. The elevation of granulocyte count generally paralleled the increase in tumor size. Postmortem examination revealed no evidence of extensive bone marrow metastases or significant suppuration in any case. The bone marrows showed varying degrees of granulocytic hyperplasia with or without a shift to the left in the maturation series. Erythroid cell hyperplasia was observed in some cases, and in one instance there was an increase in immature eosinophils. The spleen showed various degrees of infiltration by neutrophils, from minimal to extremely marked; some spleens had foci of extramedullary hemopoiesis. Colony-stimulating activity was demonstrated in tumor extracts from three of these cases and from the serum in another case. Thus, it is suggested that marked granulocytosis in these patients was caused, at least in part, by colony-stimulating factor produced by the neoplastic cells.

Quantitative study of pulmonary endocrine cells in anencephaly

Quantitative studies of pulmonary endocrine cells in 8 male autopsy cases of anencephaly were performed. The densities of pulmonary endocrine cells were expressed as the number of the total argyrophil cells/100 bronchiolar cell nuclei and as the number of the total argyrophil cells/mm bronchiole. The average values in the 8 anencephalic cases were 1.26 cells/100 nuclei and 3.56 cells/mm, and did not differ from the 1.28 cells/100 nuclei and 3.24 cells/mm in the control cases without malformation of the brain and without severe hyaline membrane disease of the lung. Furthermore, there was no significant difference in the densities of neuroepithelial bodies between the 2 groups. Immunostaining for calcitonin, bombesin, adrenocorticotropic hormone, chromogranin, and neuron-specific enolase also revealed no qualitative differences between them.It is concluded that defect and hypofunction of the hypothalamus-pituitary-adrenal axes associated with anencephaly do not have significant effects on the proliferation and differentiation of pulmonary endocrine cells in the fetus.

Effect of dietary protein on purine nucleoside phosphorylase and xanthine dehydrogenase activities of liver and kidney in chicken and pigeon

Comparative studies were made on the effects of diets of different protein contents on the activities of purine nucleoside phosphorylase and xanthine dehydrogenase of avian livers and kidneys. In chicken liver and kidney, both enzyme activities were increased with high protein diet, confirming the previous results. In pigeon liver, only purine nucleoside phosphorylase was increased but xanthine dehydrogenase activity was not detected after feeding a high protein diet, while both enzyme activities were increased in the pigeon kidney. The increase in the levels of plasma oxypurines in pigeon serum was consistent with the result that the xanthine dehydrogenase activity of pigeon was not detected in the liver but in the kidney.

Effect of glycerol on cell kinetics and tumorigenesis in mouse lung following urethan administration

Extending previous studies, we hypothesized that glycerol modulates pulmonary tumorigenesis in mice through metabolic activation in bronchiolar cells. To test this, we examined the effects of glycerol on pulmonary cell kinetics and tumorigenesis induced by urethan. Male ddY mice were given 1 mg/g urethan and/or 5% glycerol solution for a fixed period. [3H]Thymidine autoradiography revealed that glycerol administration significantly suppressed the urethan-induced facilitation of cell kinetics of the bronchiolar cells (p<0.05), but not that of the alveolar wall cells. Furthermore, glycerol did not affect urethan-induced pulmonary tumorigenesis. These findings suggest that glycerol modifies the metabolism of carcinogens in the bronchiolar epithelium.

Cancer Stem Cells in Lung Cancer: Distinct Differences between Small Cell and Non-Small Cell Lung Carcinomas

Koji Okudela, M.D., Ph.D.1, Noriyuki Nagahara, M.D., Ph.D.2, Akira Katayama, Ph.D.3, Hitoshi Kitamura, M.D., Ph.D.1 1Department of Pathology, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004 Departments of 2Environmental Medicine and 3Biological Chemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602 Japan