PubMed Health⌕ Search

Biomedical subjects

C Furihata

Publications and source records attributed to C Furihata.

At least 91 records · Page 5Linked to original sources

Effects of high fat diet on fecal contents of bile acids in rats.

The effects of dietary oils and fats used in Japan on the fecal contents of bile acids in rats were studied. F344/Du Crj female rats (8 weeks old) were fed on diet containing 20% corn oil, rape seed oil, sesame oil, soybean oil, lard, or tallow as high oil or fat diets or on 0.2% linoleic acid diet as a low fatty acid diet for 4 weeks, and then their feces were collected. Bile acids in the feces were partially purified and analyzed by high-performance liquid chromatography. Analyses showed that lard or tallow in the diet resulted in significant increases in the contents of bile acids in the feces, whereas sesame oil in the diet resulted in significant decreases in their contents.

Animals↗

Inductions of ornithine decarboxylase and DNA synthesis in rat stomach mucosa by glandular stomach carcinogens.

The inductions of ornithine decarboxylase (ODC) and DNA synthesis in the pyloric mucosa of the stomach of male F344 rats after oral administrations of chemicals were studied. The glandular stomach carcinogens N-methyl-N'-nitro-N-nitrosoguanidine, N-ethyl-N'-nitro-N-nitrosoguanidine, N-propyl-N'-nitro-N-nitrosoguanidine, 4-nitroquinoline 1-oxide and N-nitroso-N-methylurethane induced up to 100-fold increase in ODC activity in the pyloric mucosa of the stomach; the activity was maximal 24 hr after administration and returned to the control level after 48 to 72 hr. These compounds also induced 14- to 30-fold increase in DNA synthesis in the pyloric mucosa of the stomach; synthesis was maximal 16 to 24 hr after administration and returned to the control level after 144 hr. The non-gastric carcinogens 2-acetylaminofluorene, dimethylnitrosamine and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) did not induce ODC or DNA synthesis in the pyloric mucosa of the stomach. Ethyl alcohol also did not induce ODC or DNA synthesis in the pyloric mucosa of the stomach. These results and previous findings that stomach-tumor promoters such as NaCl, taurocholate, glyoxal, K2S2O5 and formaldehyde induced ODC and DNA synthesis in the pyloric mucosa of the stomach of F344 rats suggest that the inductions of ODC and DNA synthesis in the glandular stomach mucosa are markers of promotive activities of complete carcinogens and tumor promoters in the glandular stomach.

Animals↗

Immunohistochemical demonstration of pyloric gland-type cells with low-pepsinogen isozyme 1 in preneoplastic and neoplastic tissues of rat stomachs treated with N-methyl-N'-nitro-N-nitrosoguanidine.

The appearance of pyloric gland-type cells with a low pepsinogen isozyme 1 (Pg 1) content in the stomach mucosa of F344/Du rats during stomach carcinogenesis was examined by a combination of paradoxical concanavalin A (Con A) staining and immunohistochemical staining for Pg 1. Male F344 rats were given drinking water containing 100 micrograms N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7]/ml for 30 weeks and then normal tap water and were killed in week 10, 20, 30, 40, 50, or 70. Untreated rats were killed in week 30 or 70. Serial sections of pyloric mucosa were stained by paradoxical Con A staining and Pg 1 immunostaining. After MNNG treatment, tissues showing changes were classified into normal-looking pyloric mucosa with a low Pg 1 content, mucosa showing atrophic or hyperplastic changes, adenomatous hyperplasia, and adenocarcinoma. From the results of paradoxical Con A staining and Pg 1 immunostaining, the cells in lesions were classified into gastric types (surface mucous cell type and pyloric gland cell type) and intestinal types (intestinal-absorptive cell type and goblet cell type). In this experiment, the cells in lesions were mainly of the gastric cell types. All pyloric glands of control rats in weeks 30 and 70 contained class III mucins and had a high Pg 1 content demonstrated immunohistochemically. After MNNG treatment, class III mucin-positive pyloric glands with a low Pg 1 content in normal-looking pyloric mucosa were found from week 10; subsequently, their number increased with time. Changed mucosa was found from week 20, and the area of cells of the pyloric gland cell type with little or no Pg 1 in changed mucosa was about 30% of the area of cells of the pyloric gland cell type. Adenomatous hyperplasias were found from week 30; adenocarcinomas were found from week 50. Almost all cells of the pyloric gland cell type (greater than 95%) in areas of adenomatous hyperplasia and adenocarcinomas had little or no Pg 1 content. The present results suggested that the appearance of pyloric glands with a low Pg 1 content in normal-looking mucosa might be an immunohistochemically detectable preneoplastic change preceding morphologically detectable preneoplastic changes in stomach carcinogenesis.

Animals↗

Gastric and intestinal phenotypic expressions of human signet ring cell carcinomas revealed by their biochemistry, mucin histochemistry, and ultrastructure.

Gastric and intestinal phenotypic expression in 37 surgically obtained primary signet ring cell carcinomas, five of their metastases to lymph nodes, and three signet ring cell carcinomas transplanted into nude mice were determined by biochemical, mucin, histochemical, and ultrastructural studies. Crude extracts of cancer tissues were used for measurements of pepsinogen isozymes, sucrase, aminopeptidase (microsomal), and alkaline phosphatase. Histochemical staining of mucin by paradoxical concanavalin A, the galactose oxidase-Schiff sequence and sialidase-galactose oxidase-Schiff, and the periodate-borohydride technique/potassium hydroxide/periodic acid-Schiff procedure was performed. The procedures allowed clear definition of pyloric gland, surface mucous, small and large intestinal goblet, and intestinal absorptive cell types. Of 40 specimens examined, 19 consisted entirely of gastric-type cells, and three entirely of intestinal-type cells. The others consisted of mixtures of gastric and intestinal-type cells. The observed high incidence of intestinal-type cells in signet ring cell carcinomas suggested that intestinal-type cells develop independently from intestinal metaplasia within signet ring cell carcinomas (diffuse-type gastric cancers), which probably originate from nonmetaplastic gastric mucosa.

Adenocarcinoma, Mucinous↗

Immunohistochemical demonstration of induction of pyloric glands with low pepsinogen 1 (Pg 1) content in rat stomach by N-methyl-N'-nitro-N-nitrosoguanidine.

Three groups of male Fischer rats were given single doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 160 mg (group 1), 80 mg (group 2) and 40 mg (group 3)/kg body weight by gastric intubation. A fourth group was given drinking water containing 100 micrograms/ml of MNNG for 2 weeks, and a fifth group served as a control. Rats were killed in weeks 5, 8 and 12. Serial sections of the pyloric mucosa were examined by paradoxical concanavalin A (Con A) staining and pepsinogen isozyme 1 (Pg 1) immunostaining. All pyloric glands contained class III mucin as detected by paradoxical Con A staining. Most pyloric glands had a high Pg 1 content, but a few stained only weakly if at all. The percentage and number (No./500 normal-looking pyloric glands) of pyloric glands with a low Pg 1 content were 50.0 and 0.2 +/- 0.4 (week 5), 87.5 and 0.5 +/- 0.4 (week 8) and 100.0 and 1.2 +/- 1.0 (week 12) in group 1, 50.0 and 0.2 +/- 0.3 (week 8) and 87.5 and 0.5 +/- 0.4 (week 12) in group 2, and 30.0 and 0.2 +/- 0.4 (week 12) in group 4. No pyloric glands with a low Pg 1 content were found in groups 3 and 5. Thus the results showed significant dose-dependent induction (P less than 0.05-0.01) of altered pyloric glands demonstrating reduced Pg 1 content and their earlier appearance in groups given higher doses of MNNG. The results suggest that the appearance of pyloric glands with a low Pg 1 content may be a preneoplastic change in gastric carcinogenesis.

Animals↗

Application of rapid freezing followed by freeze-substitution acrolein fixation for cytochemical studies of the rat stomach.

A method involving rapid freezing followed by substitution fixation was developed, using acrolein as a fixative. This was then applied to several cytochemical stainings, and showed well preserved and clear cell structures. Membranes were apparently negatively stained and the ultrastructure of mitochondria, rough endoplasmic reticulum and Golgi apparatus was clearly discernible. The mitochondrial and cytoplasmic matrices were stained rather densely compared with routine chemically fixed preparations, implying a good preservation of matrix substances. Periodic acid-thiocarbohydrazide-silver proteinate staining was applied to the present method. The mucous granules of surface covering epithelial cells indicated fine staining of bipartite structure and the Golgi apparatus of mucous cells showed clear staining differences based on polarity. Postembedding lectin-ferritin and immunocytochemical stainings were applicable to the present preparations and stable stainings of secretory granules were obtained. A low temperature embedding material, Lowicryl K4M, was also examined. The cell preservation of these samples was not as good as those embedded in Epon, but the rough endoplasmic reticulum and Golgi apparatus of chief cells were stained with anti-pepsinogen antibody as were the secretory granules. The present method was also applicable to light microscopy.

Acrolein↗

Induction of ornithine decarboxylase and DNA synthesis in rat stomach mucosa by methylglyoxal.

Administration of methylglyoxal at doses of 300-600 mg/kg body weight by gastric tube to male F344 rats induced 100-fold increase in ornithine decarboxylase activity (formation of 682 pmol CO2/30 min/mg protein) within 7 h, 26-fold increase in DNA synthesis (incorporation of 17 800 d.p.m. of [3H]thymidine/microgram DNA) within 16 h, 16-fold increase in the labeling index of S-phase cells (increase from 1.7 to 26.5) within 16 h, and apparent unscheduled DNA synthesis within 2 h in the glandular stomach mucosa. These results suggest that methylglyoxal has potential promoter activity and may also have initiating activity in carcinogenesis in the glandular stomach.

Aldehydes↗

Potential initiating and promoting activities of diacetyl and glyoxal in rat stomach mucosa.

The potential initiating and promoting activities in the rat glandular stomach of the dicarbonyl compounds diacetyl (DA) and glyoxal (G), which are found in various heated foods, were studied. Administration of DA at doses of 300 to 1500 mg/kg body weight and of G at doses of 150 to 400 mg/kg body weight by gastric intubation to male F344 rats induced up to 100-fold increase in ornithine decarboxylase activity (formation of 195 pmol CO2/30 min/mg protein by DA and 302 pmol CO2/30 min/mg protein by G) with maxima after 16 hr. These treatments also induced a more than 10-fold increase in DNA synthesis (incorporation of 11,400 dpm of [3H]dThd/microgram DNA by DA and 15,100 dpm of [3H]dThd/microgram DNA by G) with maxima after 16 hr, and induced apparent unscheduled DNA synthesis in the pyloric mucosa of the stomach within 3 hr after administration. These results suggest that DA and G have potential tumor-promoting activities and may also have initiating activities in carcinogenesis in the glandular stomach.

Aldehydes↗

NaCl induced ornithine decarboxylase and DNA synthesis in rat stomach mucosa.

Inductions of 200-fold increase in ornithine decarboxylase activity within 6 hours and 9-fold increase in DNA synthesis within 3 hours in rat stomach mucosa were observed after a single oral dose of saturated NaCl solution. NaCl caused dose-dependent induction of ornithine decarboxylase activity at doses of 0.25 to 1. 5g /kg body weight, and of DNA synthesis at doses of 0. 5g to 1. 5g /kg body weight. Administration of 1,3-diaminopropane one hour before NaCl inhibited the induction of ornithine decarboxylase activity in the stomach mucosa 3 and 6 hours after NaCl administration, but a single dose of 1,3-diaminopropane itself induced ornithine decarboxylase after 16 hours.

Animals↗

Stable intestinal phenotypic expression of gastric and small intestinal tumor cells induced by N-methyl-N'-nitro-N-nitrosoguanidine or methylnitrosourea in rats.

On the basis of paradoxical concanavalin A (Con A) staining, the tendency of tumor cells of gastric phenotype to shift to intestinal phenotype and the stability of the latter phenotype in stomach tumors of different sizes were examined quantitatively with an image processor. Phenotypic expression of tumors of the small intestine was also studied. One hundred male Wistar rats were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 50 micrograms/ml in their drinking water for 20 weeks (group 1). Twenty male F344 rats were given methylnitrosourea (MNU) at a dose of 50 mg/kg ip twice a week for 2 weeks (group 2). Rats in group 1 were killed in week 50 of the experiment and rats in group 2 were killed in week 25. In group 1, the percentage areas of intestinal-type cells in small, medium and large adenocarcinoma of the stomach were 0.5, 2.7 and 6.6%, the differences between these values being significant (P less than 0.05-0.01). Intestinal phenotypic expression of tumor cells of the stomach is stable and the proportion of intestinal-type cells in adenocarcinomas of the stomach is higher in the larger tumors. Adenomatous hyperplasias and adenocarcinomas of the small intestine in groups 1 and 2 were all composed entirely of cells of the intestinal type. These results suggested that intestinal-type cells in adenocarcinoma of the stomach did not originate from intestinal metaplasias but from gastric-type cells in stomach adenocarcinomas.

Adenocarcinoma↗

Induction of unscheduled DNA synthesis in rat stomach mucosa by glandular stomach carcinogens.

Induction of unscheduled DNA synthesis (UDS) (repair DNA synthesis) in stomach pyloric mucosa of the F344/- DuCrj rat was examined in in vitro organ cultures in the presence of tritiated thymidine ([3H]dThd) and hydroxyurea after administration of chemical carcinogens in vivo. The DNA fraction was extracted from the cultured tissue, and the incorporation of [3H]dThd into DNA was determined in a liquid scintillation counter. DNA concentration was determined spectrophotometrically with either diphenylamine or 3,5- diaminobenzoic acid. A good correlation between induction of UDS and site specificity of carcinogens was observed. The glandular stomach carcinogens N-methyl-N'-nitro-N-nitrosoguanidine (CAS: 70-25-7), N-ethyl-N'-nitro-N-nitrosoguanidine (CAS: 63885-23-4), N-propyl-N'-nitro-N-nitrosoguanidine, 4-nitroquinoline 1-oxide (CAS: 56-57-5), and N-nitroso-N-methylurethane (CAS: 615-53-2) induced UDS in the pyloric mucosa of the stomach. UDS could be detected 2-4 hours after administration of carcinogens in vivo by the present method. The forestomach carcinogens 1-methyl-1-nitrosourea (CAS: 684-93-5) and aristolochic acid (CAS: 1398-06-7) and the nongastric carcinogens 2-acetylaminofluorene (CAS: 53-96-3), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, 3-amino-1-methyl-5H-pyrido[4,3-b]indole, and dimethylnitrosamine (CAS: 62-75-9) did not induce UDS in the pyloric mucosa.

Animals↗

Gastric- and intestinal-type properties of human gastric cancers transplanted into nude mice.

The gastric- and intestinal-type properties of 15 human gastric cancers, which were transplanted into nude mice, were studied biochemically and histologically. Enzyme activities were determined in the crude extracts of cancer tissues: pepsinogen isozymes as gastric marker enzymes; and sucrase, aminopeptidase (microsomal), and alkaline phosphatase as intestinal marker enzymes. By hematoxylin and eosin staining and paradoxical concanavalin A staining, gastric cancer tissues were classified into gastric type (pyloric gland cell type and surface mucous cell type) and intestinal type (goblet cell type and intestinal absorptive cell type). On the basis of their properties, human gastric cancers were classified into four types: (a) intestinal type; (b) gastric type; (c) intestinal plus gastric type; and (d) unclassified type, showing no gastric- or intestinal-type properties. Of six well-differentiated adenocarcinomas, four were of intestinal type, one of gastric type, and one of intestinal plus gastric type. All of the intestinal-type carcinomas showed sucrase activity. Of the three signet ring cell carcinomas, one was classified as a gastric type, one as an intestinal plus gastric type, and one as an unclassified type. Of the six poorly differentiated adenocarcinomas, five were of the intestinal type and one of the unclassified type. The present results clearly showed the appearance of intestinal-type properties in gastric cancer cells not only in so-called intestinal-type carcinomas, but also in diffuse-type carcinomas.

Adenocarcinoma↗

Immunocytochemical localization of pepsinogen in rat stomach.

The localization of pepsinogen in rat stomachs was investigated by a postembedding immunoferritin method. When the preparations embedded in Epon were used, the secretory granules of chief cells were stained heavily and the granules of mucous neck cells were stained moderately. The secretory granules of cells intermediate between mucous neck cells and chief cells showed a bizonal staining; the electron dense parts were stained heavily and the electron lucent parts were stained moderately. The secretory granules of pyloric gland cells, on the other hand, were labeled faintly. However, the secretory granules of surface mucous cells, foveolar mucous cells, endocrine cells, cardiac mucous cells and cardiac serous cells were not stained by the method. The protein A-gold method showed a similar staining pattern of pepsinogen to that of the immunoferritin method. When the samples embedded in Lowicryl K4M were used to enhance the stainability of pepsinogen, essentially the same staining pattern as that of the samples embedded in Epon was obtained. In addition, the Golgi apparatus and the rough surfaced endoplasmic reticulum were more easily stained.

Animals↗