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C Furihata

Publications and source records attributed to C Furihata.

At least 73 records · Page 4Linked to original sources
PubMed1989

Inductions of ornithine decarboxylase and replicative DNA synthesis but not DNA single strand scission or unscheduled DNA synthesis in the pyloric mucosa of rat stomach by catechol.

The possible tumor-promoting and genotoxic activities of catechol were examined. Administration of catechol by gastric intubation at doses of 10 to 90 mg/kg body weight to male F344 rats induced up to 19-fold increase in ornithine decarboxylase activity with a maximum after 8 h and up to 8-fold increase in replicative DNA synthesis with a maximum after 24 h in the pyloric mucosa of the stomach. These results suggest that catechol has tumor-promoting activity in the pyloric mucosa of rat stomach. However, its administration at doses of 37.5 to 90 mg/kg body weight did not induce DNA single strand scission in the pyloric mucosa as determined by the alkaline elution method after 2 and 6 h or unscheduled DNA synthesis examined after 2 and 12 h.

Animals↗
PubMed1989

Various sodium salts, potassium salts, a calcium salt and an ammonium salt induced ornithine decarboxylase and stimulated DNA synthesis in rat stomach mucosa.

Studies were made on the possible tumor-promoting activities of various salts of food additives in the glandular stomach mucosa of F344 male rats after their administration by gastric intubation. Up to 100-fold increases in ornithine decarboxylase (ODC) activity in the pyloric mucosa of the stomach with maxima after 8 h were observed after administration of sodium acetate at doses of 3.68-13.6 mmol/kg body weight, sodium L-ascorbate at doses of 8.55-17.1 mmol/kg body weight, Na2CO3 at doses of 4.73-14.2 mmol/kg body weight, sodium L-glutamate at doses of 12.8-17.1 mmol/kg body weight, sodium sorbate at doses of 8.92-17.1 mmol/kg body weight and (NH4)2SO4 at doses of 7.56-20.1 mmol/kg body weight. Increases of up to 100-fold in ODC activity with maxima after 16 h were also observed after intubation of KCl at doses of 10.1-22.0 mmol/kg body weight, K2SO3 at doses of 2.84-8.45 mmol/kg body weight, K2S2O5 at doses of 2.25-6.75 mmol/kg body weight and CaCl2 at doses of 2.0-4.08 mmol/kg body weight. Sodium acetate at a dose of 11.0 mmol/kg body weight, KCl at a dose of 20.1 mmol/kg body weight, K2S2O5 at a dose of 5.40 mmol/kg body weight and CaCl2 at a dose of 3.4 mmol/kg body weight induced up to 10-fold increase in DNA synthesis in the pyloric mucosa of the stomach with maxima after 16-24 h. These results suggest that these salts of food additives may, like NaCl, have tumor-promoting activities in the pyloric mucosa of rat stomach.

Animals↗
PubMed1988

Cell-specific hypomethylation of the pepsinogen gene in pepsinogen-producing cells.

The pepsinogen gene is hypomethylated in the stomach, in which it is expressed. For demonstration that this hypomethylation of the pepsinogen gene in the stomach reflects pepsinogen-producing cells, we analyzed fractions of dispersed mucosal cells with various contents of pepsinogen-producing cells prepared from guinea pig stomach by centrifugal elutriation. mRNA expression and the extent of hypomethylation of the pepsinogen gene in each fraction was closely correlated with the content of pepsinogen-producing cells. These results suggested hypomethylation of the pepsinogen gene in pepsinogen-producing cells and differential pepsinogen gene methylation in cell subpopulations in the stomach.

Animals↗
PubMed1988

Enzyme-linked immunosorbent assays for serum pepsinogens I and II using monoclonal antibodies--with data on peptic ulcer and gastric cancer.

Serum pepsinogen I and pepsinogen II levels in 369 healthy controls, 38 duodenal ulcer, 30 gastric ulcer and 46 stomach cancer including 21 early and 25 advanced gastric cancer patients were measured by enzyme-linked immunosorbent assays using pepsin moiety-reacting monoclonal antibodies to pepsinogens I and II. Serum pepsinogen I and pepsinogen II levels were higher in the duodenal and gastric ulcer groups than in the control. Although there was no significant difference in serum pepsinogen II between stomach cancer and control, serum pepsinogen I was significantly lower in the former than in the latter and also in advanced gastric cancer than in early gastric cancer. A specific negative correlation of serum pepsinogen I with patient age was observed in stomach cancer but not in peptic ulcer or control groups. Receiver operating characteristic analysis was performed and indicated that serum pepsinogen I, compared with serum pepsinogen II or the pepsinogen I/pepsinogen II ratio, is the most effective marker for stomach cancer.

Antibodies, Monoclonal↗
PubMed1988

DNA methylation and expression of the rat pepsinogen gene in embryonic, adult, and neoplastic tissues.

The relationship between methylation and expression of rat pepsinogen 1 (Pg1) genes was investigated in various tissues. On Northern blotting with a Pg1 complementary DNA probe, Pg1 mRNA was detected only in the glandular stomach of normal rats. Methylation analysis with Msp1/HpaII and Hha1 revealed tissue specific methylation patterns of Pg1 genes with less methylated in the stomach than in other normal tissues not expressing the genes. During stomach development, there was a progressive increase in the Pg1 mRNA level that almost coincided with change in the mucosal pepsinogen level and progressive demethylation after the onset of transcription. Thus, there was an inverse correlation between methylation and expression of Pg1 genes, suggesting a role of DNA methylation in Pg1 gene regulation during normal differentiation, although not its primary role in gene activation. There was no detectable Pg1 mRNA in either primary or transplanted stomach cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine. The methylation patterns of Pg1 genes were different from those of normal tissues that expressed the gene and of those that did not and no simple correlation was observed between methylation and expression of Pg1 genes. This result is consistent with a previous finding that DNA methylation is deranged in tumor cells.

Animals↗
PubMed1988

Hypomethylation and expression of pepsinogen A genes in the fundic mucosa of human stomach.

We have examined the correlation between the extents of methylation and expression of pepsinogen A genes in normal human tissues. Expression of pepsinogen A mRNA was detected only in the fundic mucosa of the stomach and both CCGG and GCGC sites in the genes region were less methylated in the fundic mucosa than in other non-expressing tissues. Thus, there was an inverse correlation between the extents of methylation and expression of pepsinogen A genes and the role of DNA methylation in the regulation of pepsinogen A genes expression during normal differentiation was suggested.

DNA↗
PubMed1988

Coefficient induction of pepsinogen 1-decreased pyloric glands and gastric cancers in five different strains of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine.

Sequential changes of numbers of pepsinogen 1 (Pg 1)-decreased pyloric glands (PDPG) detected by immunohistochemistry and of the incidence of gastric carcinomas were examined in five different strains of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG;CAS:70-25-7). Male SD (Crj:CD), WKY (WKY/NCrj), Lewis (LEW/Crj), Wistar (Crj:Wistar) and F344 (F344/DuCrj) rats (40 per strain), were given drinking water containing 100 micrograms/ml MNNG for 30 weeks and then normal tap water, and were killed at week 10, 30 and 50 of the experiment. Adenocarcinomas of the glandular stomach were found in nine of 15 SD rats (60%), in eight of 12 WKY rats (67%), in eight of 15 Lewis rats (53%), in three of 13 Wistar rats (23%) and in one of 18 F344 rats (6%) at week 50. These incidences of carcinomas in SD, WKY and Lewis were significantly higher (P less than 0.01) than that in F344 rats. From week 10, the numbers of PDPG in SD, WKY and Lewis rats were significantly greater (P less than 0.01) than that in F344 rats. From week 30, the numbers of PDPG in Wistar rats were also significantly greater (P less than 0.05-0.01) than that of F344. The susceptibility of rats to induction of gastric carcinoma by MNNG correlated with the susceptibility to induction of PDPG by MNNG in each strain, suggesting that induction of PDPG is a preneoplastic change in chemical gastric carcinogenesis.

Animals↗
PubMed1988

Possible tumour-initiating and -promoting activities of 3-diazo-N-nitrosobamethan in rat stomach mucosa.

3-Diazo-N-nitrosobamethan (DNB), a mutagen produced by nitrite treatment of bamethan, a cardiovascular drug, induced unscheduled DNA synthesis in the pyloric mucosa of the stomach of male F344 rats 2 h after its administration by gastric tube at doses of 75 to 225 mg/kg body wt. DNB at a dose of 225 mg/kg body wt induced up to a 13-fold increase in replicative DNA synthesis with a maximum at 16 h after its administration. Moreover at doses of 75 to 225 mg/kg body wt, it induced up to a 12-fold increase in ornithine decarboxylase activity with a maximum after 16 h. The present results suggest that DNB has possible tumour-initiating and -promoting activities in the pyloric mucosa of the rat stomach. However, the possible risks to patients posed by clinical use of bamethan cannot be evaluated until further work is completed.

Animals↗
PubMed1988

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

Administration of formaldehyde at doses of 11 to 110 mg/kg body weight by gastric intubation to male F344 rats induced up to 100-fold increase in ornithine decarboxylase activity with a maximum after 16 hr and up to 49-fold increase in DNA synthesis with a maximum after 16 hr in the pyloric mucosa of the stomach. These results suggest that formaldehyde has tumor-promoting activity in carcinogenesis in the glandular stomach.

Animals↗
PubMed1988

Pepsinogens I and II in gastric cancer: an immunohistochemical study using monoclonal antibodies.

Monoclonal antibodies were used to examine the immunohistochemical expression of pepsinogens I and II in 31 early and 76 advanced gastric cancers. Of the 107 carcinomas studied, 19 contained pepsinogen II and only 3, found exclusively in pepsinogen II-positive cases, contained pepsinogen I. Gastric cancer produces pepsinogen II more frequently than pepsinogen I, and production of the latter is significantly associated with the former. Histologically, there were 54 intestinal-type and 53 diffuse-type cancers. The former produced pepsinogen II more frequently than the latter. In the diffuse type, the four pepsinogen II-positive cases were found exclusively in females. Although the pepsinogen expression was independent of the macroscopic features in advanced gastric cancer, it was found that the protruded-type early gastric cancer produced pepsinogen II more frequently than the depressed type. Incidences of pepsinogen positivity were not different between early and advanced gastric cancers or between cancers with or without lymph node metastasis, suggesting that production of pepsinogen is independent of tumor growth.

Aged↗
PubMed1987

Enzyme-linked immunosorbent assay of serum pepsinogen I.

A hybridoma monoclonal antibody against human pepsinogen I was used to develop an enzyme-linked immunosorbent assay for pepsinogen I in serum. In the two-step competitive procedure using antimouse immunoglobulin F(ab')2 fragment coupled to alkaline phosphatase, the measurable assay range was 8-256 micrograms/l. No cross-reactivity with rat pepsinogen 1, human pepsinogen II, gastrin I, bombesin, somatostatin and peptide YY was shown. However, there was slight cross-reactivity (0.09%) with porcine pepsinogen. The coefficients of variation within and between series were 7.6% and 13.0%. This enzyme-linked immunosorbent assay for serum pepsinogen I correlated positively with radioimmunoassay (r = 0.87, n = 92). The concentration range of serum pepsinogen I in 354 healthy controls was 15-100 micrograms/l with a lognormal distribution. Serum pepsinogen I levels were significantly higher in the subjects who developed active duodenal ulcer or active gastric ulcer, but significantly lower in those who had gastric cancer, than in control subjects.

Adult↗
PubMed1987

Serum pepsinogens as a screening test of extensive chronic gastritis.

The serum level of pepsinogen I (PG I) and pepsinogen II (PG II), and the PG I/PG II ratio were compared with the surface area of the fundic mucosa, as determined endoscopically by the Congo red staining method. Reduction in the area of the fundic mucosa due to gastritis was associated with stepwise reduction in the PG I levels and the PG I/PG II ratios. Reduction in the area of the fundic mucosa was also associated with decreases in the basal acid output, maximal acid output (MAO), the basal pepsin output and the stimulated pepsin output. The best sensitivity and specificity levels for the diagnosis of normal mucosa and severe gastritis were obtained with the PG I/PG II ratio and the MAO. A retrospective study of 58 patients with gastric cancer and 162 cancer-free patients showed that a PG I/PG II ratio identified 86.2% of all carcinomas and 87.5% of early carcinomas. Although this test gave a positive rate of 36% among the cancer-susceptible age group controls, its use would lower the cost of mass screening by targeting a smaller test population.

Chronic Disease↗
PubMed1987

Complete and incomplete pyloric gland metaplasia of human gallbladder.

The features of pyloric gland metaplasia in the gallbladder epithelium were studied by histochemical staining for mucin and the immunoperoxidase method for pepsinogens (Pg) I and II. Pyloric gland metaplasia was found in 48 of 72 gallbladders removed surgically. All the pyloric gland metaplastic cells contained class III mucin demonstrated by paradoxical concanavalin A (Con A) staining. Pyloric gland metaplasia was classified into complete and incomplete types on the basis of the immunohistochemical reactivities of Pgs I and II: The complete type of pyloric gland metaplasia contained neutral mucins and weak Pg I and strong Pg II activities, like normal pyloric gland cells. Almost all specimens of the incomplete type of pyloric gland metaplasia contained acid mucins and were further classified into two types: an incomplete type 1, which had Pg II but no Pg I activity, and an incomplete type 2, which had no Pg I or II activity.

Epithelium↗
PubMed1987

Use of in vivo/in vitro unscheduled DNA synthesis for identification of organ-specific carcinogens.

There are still only a few in vivo short-term assay methods for predicting potential organ-specific carcinogens and mutagens in mammals, although such methods are required for evaluating the in vivo effects of in vitro mutagens. In the in vivo/in vitro UDS assay methods described here, chemicals are given to experimental animals and induction of UDS in target organs is determined by in vitro organ culture or primary cell culture in the presence of [3H]dThd. Incorporation of [3H]dThd into DNA is measured with a liquid scintillation counter or by autoradiography. These methods have now been applied to the glandular stomach, forestomach, colon, liver, kidney, pancreas, tracheal epithelium, nasal epithelium, and spermatocytes. With minor modifications, they may also be applied to other organs. The present review shows that induction of UDS in various organs correlated well with the induction of cancer in these organs. The present authors have used the present methods to identify some potential organ-specific mutagens and carcinogens in mammals. The present authors found that three dicarbonyl compounds, glyoxal, methylglyoxal, and diacetyl, induced apparent UDS and TDS in the glandular stomach, and other groups found that 2-NT, MA6BT, and CNEt6BT induced UDS in the liver. These in vivo/in vitro UDS assays are better than in vitro UDS assay for identification of potential organ-specific mutagens and carcinogens in mammals and are especially useful for identifying potential mutagens and carcinogens that are specific for certain organs, such as the stomach, liver, and kidney. They are also useful for examining the potential mutagenicities and carcinogenicities of carcinogen analogs. However, these methods are not suitable for general in vivo screening because they are not yet available for all organs. A further advantage of the methods is that they can be used to examine larger numbers of animals at one time than other methods for detecting DNA damage, such as alkaline elution or alkaline sucrose density gradient centrifugation. Glyoxal enhanced cancer induction in the glandular stomach by the administration of a limited amount of MNNG and then glyoxal afterward in the two-stage stomach carcinogenesis.

Animals↗
PubMed1987

Potential tumor-promoting activity of bile acids in rat glandular stomach.

The potential tumor-promoting and -initiating activities of bile acids in the glandular stomach mucosa of F344 rats after administration by gastric intubation were studied. Taurocholic acid sodium salt at doses of 300 to 1200 mg/kg body weight and glycocholic acid sodium salt at doses of 400 to 1200 mg/kg body weight induced up to 100-fold increases in ornithine decarboxylase activity with maxima after 4 hr and up to 10-fold increases in replicative DNA synthesis with maxima after 16-17 hr in the pyloric mucosa of the stomach. Taurodeoxycholic acid sodium salt, taurochenodeoxycholic acid sodium salt and glycocholic acid also induced high ornithine decarboxylase activity, and glycodeoxycholic acid sodium salt and glycochenodeoxycholic acid sodium salt caused slight induction of ornithine decarboxylase activity, but taurolithocholic acid sodium salt did not induce ornithine decarboxylase activity at all in the pyloric mucosa of the stomach. Glycocholic acid sodium salt did not induce unscheduled DNA synthesis in the pyloric mucosa of the stomach. The present results suggest that six bile acids, but not taurolithocholic acid sodium salt, have potential tumor-promoting activities in the pyloric mucosa of rat stomach and that glycocholic acid sodium salt has no potential tumor-initiating activity in the pyloric mucosa of rat stomach.

Animals↗
PubMed1987

Enhancing effects of N-ethyl-N'-nitro-N-nitrosoguanidine and sodium taurocholate on development of pepsinogen 1 decreased pyloric glands in rats initiated with N-methyl-N'-nitro-N-nitrosoguanidine.

Sequential quantitative analyses were made of pepsinogen 1 (Pg 1) decreased pyloric glands after treating male WKY rats first with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and then with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) as a second gastric carcinogen or sodium taurocholate (Na-TC) as a gastric promoter. Animals received a single dose of MNNG (160 mg/kg body weight) by gastric intubation followed two weeks later by either ENNG in drinking water (100 micrograms/ml) (group 1), basal diet containing 0.25% Na-TC (group 2), or basal diet and tap water (group 3), from weeks 3 to 24. Animals were sacrificed at weeks 8, 12, 16, 20 and 24. Sections of the pyloric mucosa were investigated for Pg 1 immunostaining. In comparison with group 3, induction of Pg 1 decreased pyloric glands was significantly enhanced by ENNG from week 8 and by Na-TC from week 16. The former exerted a significantly stronger effect at each time point. The results suggest that Pg 1 decreased pyloric glands represent a good marker for early detection of gastric carcinogens and promoters in in vivo test systems.

Animals↗
PubMed1987

Inductions of ornithine decarboxylase and DNA synthesis in rat stomach mucosa by 1-nitrosoindole-3-acetonitrile.

Administration of 1-nitrosoindole-3-acetonitrile (NIAN) at doses of 40 to 300 mg/kg body weight by gastric intubation to male F344 rats induced up to 100-fold increase in ornithine decarboxylase activity with a maximum after 24 hr and up to 10-fold increase in DNA synthesis with a maximum after 16 hr in the pyloric mucosa of the stomach. These results suggest that NIAN has potential tumor-promoting activity in carcinogenesis in the glandular stomach.

Acetonitriles↗