Fat-storing cells (lipocytes) in the liver: their role in vitamin A storage and fibrogenesis.
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Biomedical subjects
Publications and source records attributed to T Inouye.
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Hepatocellular necrosis in carbon tetracholride-induced injury of rats is associated with an accumulation of lipocytes (perisinusoidal cells or Ito cells) containing fat droplets and giving vitamin A fluorescence. In the subsequent formation of connective tissue septa, transitional cells having morphologic characteristics of lipocytes and fibroblasts are abundant and are associated with the appearance of type III collage-. The features suggest that the lipocyte is the precursor of the fibroblasts responsible for parenchymal fibrillogenesis and under these conditions forms type III collagen. The process is a postulated link between hepatocellular necrosis and fibrosis.
N-(Phosphonacetyl)-L-aspartate (PALA) is an analog of the transition state for the aspartate transcarbamylase reaction and has been reported previously to be a potent and specific inhibitor of de novo pyrimidine nucleotide biosynthesis. It is now shown that PALA has considerable antitumor activity against certain transplantable tumors in mice. PALA, unlike other antimetabolites, was less effective against ascitic leukemias than against two solid tumors, B16 melanoma and Lewis lung carcinoma. Another solid tumor, Ridgway osteogenic sarcoma, which is sensitivie to many established chemotherapeutic agents, did not respond to PALA. Daily or intermittent treatment with PALA did not significantly increase the life-span of mice bearing i.p. leukemia L1210. The survival time of mice bearing i.p. P388 leukemia was prolonged by PALA treatment by up to 64%. In a number of experiments mice bearing i.p. B16 melanoma survived 77 to 86% longer than did controls when treated with PALA (490 mg/kg) on Days 1, 5, and 9. Lewis lung carcinoma, a tumor refractory to most established antineoplastic agents, was highly sensitive to PALA. Treatment on Days 1, 5, and 9 following s.c. implantation of Lewis lung carcinoma was curative to 50% of the mice. If treatment was delayed until s.c. Lewis lung tumors had reached about 500 mg, PALA neither cured the mice nor produced significant tumor regression. However, extensive delay of tumor growth and prolongation of survival were still observed.
Relationship between the survival time of L-1210-bearing mice and myelosuppression of normal mice after combination chemotherapy was studied. In a variety of combinations of 6-mercaptopurine, 6-thioguanine, and cyclophosphamide, a combination of cyclophosphamide and 6-thioguanine produced the highest increase in life span (ILS) and the highest number of 60-day survivors of all. In contrast, a combination of 6-mercaptopurine and 6-thioguanine showed as low as ILS as did single agents. A combination of 6-mercaptopurine, cyclophosphamide, and 6-thioguanine exhibited the second best effect on survival time of leukemic mice. However, in myelosuppression as measured by changes in the total number of nucleated cells, in the number of hematopoietic colony-forming cell, and in peroxidase level of femoral bone-marrow, the combination of 6-mercaptopurine and 6-thioguanine showed no more toxicity than the other 2-drug combinations. In addition to these findings, the presence of a striking difference in the cell number in ascitic fluid of leukemic mice among the animals given 6-thioguanine, and those given other 2- or 3-drug combinations may suggest that the difference in the antileukemic activity is not due to the difference in the toxicity against the host, but due to the difference in the activity of direct action of combined drugs on leukemic cells in the peritoneal cavity or in other sites.
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This report describes the histopathological changes in the temporal bone of a 71-year-old man who died of meningitis and epidural abscess complicated by primary squamous cell carcinoma of the middle ear. The present case is unusual and differs somewhat from previously reported cases of the primary squamous cell carcinoma of the middle ear in three respects: 1) an extensive invasion of the cancer into the membranous labyrinth, 2) cholesterol deposits in the cochlear spiral canal, and 3) presence of ossifying labyrinthitis. Among these findings, extensive involvement of the inner ear by cancer destroying the lower part of the otic capsule is particularly unusual. It is assumed that squamous cell carcinoma overcame the biological resistance to neoplastic infiltration which probably exists in the otic capsule and the membranous labyrinth.