[Establishment of test methods for examining promoters of hepatocarcinogenesis--promoting effects of phenobarbital, butylated hydroxytoluene and barbital].
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Biomedical subjects
Publications and source records attributed to F Furukawa.
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Trypsinized guinea pig epidermal cells were separated by velocity sedimentation at unit gravity. Based on the relationship between cell size and both morphological and functional aspects of differentiation, the cells were classified as lower (a diameter less than 12.5 micron), middle (a diameter between 12.5 and 15 micron), and upper (a diameter greater than 15 micron) epidermal cells. Fresh cells exposed to rhodaminated concanavalin A (Con A) were sedimented and reacted with fluoresceinated anti-Con A serum to distinguish cell surface Con A from intracellular lectin. Labeling at 4 degrees C resulted in a uniform surface distribution of Con A irrespective of cell size. After a 1-hr incubation of Con A-labeled cells in lectin-free medium at 37 degrees C, lower epidermal cells and approximately half of middle epidermal cells internalized Con A/receptor complexes by endocytosis while lectin remained diffusely on the remainder of middle epidermal cells and upper epidermal cells. By electron microscopy, ferritin-Con A was clustered on surface areas and invaginations of the plasma membrane before being endocytosed. We concluded that the differentiation of epidermal cells was accompanied by progressive decrease in endocytosis and, most probably, mobility of Con A receptors.
In 79 patients with leprosy a significant increase of anti-extractable nuclear antigen (ENA) antibodies and circulating immune complexes (CIC) was found. No correlation between CIC and anti-ENA antibodies was demonstrable. Since such a correlation is known from antinuclear antibodies and CIC in patients with systemic lupus erythematosus, it appears likely that anti-ENA antibodies do not play a causative role in CIC-mediated pathogenesis of leprosy.
Since Askanazy's first report on a case of primary intracranial choriocarcinoma in 1906, more than 60 cases have been reported so far. We add to that a case of intrasellar choriocarcinoma with suprasellar extension: A 12-year-old girl showed cranial nerve palsies, hypopituitarism, and abnormally high titers of human chorionic gonadotropin (HCG) in blood and in cerebrospinal fluid (CSF). She died 3 months after surgery. At autopsy, an intra- and suprasellar choriocarcinoma, which penetrated through the clivus into the cerebellopontine angle and metastasized remotely to the lungs, was confirmed. This rare case is presented with a thorough review of the literature.
The effects of timing of a single intragastric application of dibutyltin dichloride, at a dosage of 30 mg/kg body wt, on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinomas have been studied in female Syrian golden hamsters. Dibutyltin dichloride, which has been shown to produce selected bile duct injury, was administered either 1 week before or 1 week after a single injection of BOP (20 mg/kg body wt). Control hamsters were injected with BOP alone or were given dibutyltin dichloride alone. The incidence of ductal adenocarcinomas strikingly decreased in hamsters when dibutyltin dichloride was ingested after BOP treatment, but remained unaffected when dibutyltin dichloride was given before carcinogen treatment. Two cases of sarcoma were observed in the group treated with dibutyltin dichloride before BOP injection. The incidence of insulomas, which were considered as spontaneous tumors, was not influenced by dibutyltin dichloride. These results showed that intragastric application of dibutyltin dichloride after BOP treatment significantly reduced the induction of pancreatic cancer. These findings do not support speculations based on epidemiologic studies as to a promoting effect of cholestasis.
Neutropenia is rarely associated with cephalosporins. We report a case of neutropenia associated with cefotaxime. A seven-year-old boy was admitted to the Chidoribashi Hospital with suspected septicemia. Cefotaxime 2 g/d was started. On day 18, neutropenia associated with cefotaxime was suspected. On day 22, the patient was transferred to Fukuoka Children's Hospital because of continuing neutropenia and eosinophilia. In Fukuoka Children's Hospital, bone marrow puncture revealed severe bone marrow depression. After one month, the patient was discharged. When we considered case reports of granulocytopenia, leukopenia, and agranulocytosis associated with cephalosporins, we found two types of leukopenia. One is the granulocytopenic type and the other is the neutropenic type. In diagnosing leukopenia due to cephalosporins, an increased percentage of eosinophils in white-blood-cell analysis is significant.
We designed a polyethylene glycol precipitation method for detecting retroviral gp70-anti-gp70 immune complexes (gp70 IC) in the circulation of mice. To determine the genetic contribution of NZB and NZW strains to the spontaneous occurrence of circulating gp70 IC in NZB X NZW (B/W)F1 hybrids, we measured these IC in female NZB, NZW, (NZB X NZW)F1 (B/W F1), B/W F1 X NZW backcross, and B/W F1 X NZB backcross mice. The highest amounts of gp70 IC were found in B/W F1 and the lowest in NZW mice, and the order of the average serum levels was B/W F1, B/W F1 X NZB, B/W F1 X NZW, NZB, and NZW. Genetic analyses suggested that two major dominant genes, one from NZB and the other from NZW, are involved in the formation of these gp70 IC. A single dominant gene of NZB strain determines the formation of these IC, and the magnitude is to a great degree modified (intensified) by the NZW gene. In addition, statistical analyses of data obtained in the studies of B/W F1 X NZW backcrosses suggested the presence of one additional dominant NZB gene that also regulates the magnitude of gp70 IC formation in concert with the other NZB gene. Since all these New Zealand mice share a high serum level of free gp70, the formation of gp70 IC represents the gene action on the production of anti-gp70 antibodies. Linkage studies showed that both of the major NZB and NZW genes are loosely linked to the H-2 complex but not to either the Mup-1 or coat color gene loci examined. The incidence of proteinuria correlated well with the serum level of gp70 IC in both B/W F1 X NZW and B/W F1 X NZB backcross mice.
The carcinogenicity of fish meal pyrolysate was examined in noninbred Syrian golden hamsters of both sexes. Hamsters were given a diet containing 5%, 10%, 20% or 40% fish meal pyrolysate for 102 weeks in Experiment 1, and 10% or 20% fish meal pyrolysate for 112 weeks in Experiment 2. Hamsters in control groups in both experiments were fed a normal basal diet. Various tumors were found in both experimental and corresponding control groups, but there was no significant difference in the incidence of any tumors between the experimental and control groups. Thus, the fish meal pyrolysate tested was not carcinogenic to Syrian golden hamsters under these conditions. In male hamsters the severity and incidence of fatty degeneration of the liver and chronic nephropathy tended to correlate with the concentration of fish meal pyrolysate in the diet. With females, however, the correlation was not so clear. In neither sex did the presence of atrial thrombosis or systemic amyloidosis appear to be dependent on the dietary concentration of fish meal pyrolysate.
Thiram was added at levels of 0.1 and 0.05% to the diet of F-344 rats for 2 years. The results indicated that thiram significantly reduced the incidence of spontaneous leukemia, and also tended to reduce the incidences of pituitary and thyroid tumors.
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The influence of sodium chloride on chemical carcinogenesis of the gastroduodenal tract was examined in male outbred Wistar rats exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (100 mg/liter) for 20 weeks. Sodium chloride given concomitantly with MNNG during the first 20 weeks of the experiment increased both the incidence and the size of tumors at 40 weeks. However, sodium chloride given after MNNG during the second 20 weeks of the experiment did not enhance tumor development. This study indicates that, although sodium chloride given with MNNG enhances tumor development, sodium chloride does not promote gastric carcinogenesis.
Spontaneous tumors in 296 male and 297 female F-34/DuCrj rats used as control groups in six carcinogenicity tests were tabulated and evaluated. In males the most frequent tumors were testicular interstitial cell tumors, followed by mammary fibromas and fibroadenomas, mononuclear cell leukemias, pheochromocytomas, C-cell adenomas of the thyroid, pituitary adenomas, preputial adenomas, neoplastic nodules of the liver, and lung adenomas. In contrast, in females pituitary adenomas, uterine endometrial stromal polyps, mammary fibroadenomas, mononuclear cell leukemias and C-cell adenomas were the most common. Various other tumors of almost all other organs and/or tissues were found, although their incidences were low. Variability in the rates of incidence in some tumors was observed in different control groups.
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