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Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 595 records · Page 33Linked to original sources
PubMed1984

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↗
PubMed1984

Evaluation of a histologic classification of mouse liver tumors based on pyruvate kinase isozymes and status of host lipids.

The histologic classification of mouse liver tumors, i.e., hepatic nodules type 1 and type 2 and hepatocellular carcinomas, was evaluated by a comparison of several biologic and biochemical markers that have been shown to be useful for the grading of tumor malignancy. The liver tumors were induced by N,N'-2,7-fluorenylenebisacetamide (CAS: 304-28-9; N,N'-fluoren-2,7-ylenebisacetamide) administration to male CD-1 mice. The ability to induce L-type pyruvate kinase activity in response to a high-carbohydrate diet disappeared in almost all the liver tumors. However, fairly good correlations were observed between the histologic classification and the relative weights of liver and intraperitoneal fat pads, between the histologic classification and the level of serum total cholesterol, and between the histologic classification and the K-type pyruvate kinase activity. The results suggest that the present histologic classification reflects the degree of tumor malignancy, and therefore, it would be useful for the classification of mouse liver tumors.

Animals↗
PubMed1984

Changes in molecular forms of rat hepatic glutathione S-transferase during chemical hepatocarcinogenesis.

Changes in molecular forms of hepatic cytosolic glutathione S-transferases (GST) during rat chemical hepatocarcinogenesis were investigated. GST activities toward 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene increased with the increased area of gamma-glutamyltranspeptidase-positive foci and hyperplastic nodules induced by diethylnitrosamine followed by 2-acetylaminofluorene plus hepatectomy. Among GSTs with high activities toward 1,2-dichloro-4-nitrobenzene, which were separated by carboxymethyl Sephadex column chromatography, the activity of GST-A ( YbYb ) markedly increased with increased activity towards 1,2-dichloro-4-nitrobenzene in livers bearing foci and nodules and in isolated nodules and hepatomas, while activities of GST-C ( YbYb ') and -D (Yb'Yb') changed little. It was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional gel electrophoresis that Yb as well as Ya , a subunit of ligandin ( YaYa ) and GST-B ( YaYc ), increased in livers bearing foci and nodules, while Yc as well as Yb' changed little. A new placental GST form (GST-P), which has a subunit molecular weight of 21,500 or 26,000, according to the marker proteins used, and neutral pls of 6.8 and 6.3, is immunologically different from any form of basic GSTs and is very low in normal liver; also, it was markedly induced in livers bearing foci and nodules and in well-differentiated hepatomas but not by short-term administration of drugs such as 2-acetylaminofluorene, in contrast to GST-A and ligandin. These results indicate that GST-A and more especially GST-P could be new preneoplastic marker enzymes for chemical hepatocarcinogenesis.

2-Acetylaminofluorene↗
PubMed1983

Histopathological classification of spontaneous hyperplastic liver nodules in slaughtered swine.

Thirty-two cases of spontaneous hyperplastic nodules of the liver found in slaughtered swine were classified on the basis of their histological characteristics into two main types, non-fibrous and fibrous nodules, according to their content of fibrous tissue. These two main types were further divided into two subgroups: type 1, a nodule mainly consisting of liver cells arranged in a single liver cell plate, and type 2 nodule with a multiple liver cell plate architecture. All 12 fibrous nodules were of type 2; of the 20 non-fibrous nodules 9 were of type 1 and 11 were type 2 or intermediate. The histopathology of these lesions is discussed in relation to pre-neoplastic and neoplastic characters.

Animals↗
PubMed1983

Dose and sex dependent effects of 2-acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene and DL-ethionine in induction of gamma-glutamyl transpeptidase-positive liver cell foci in rats.

The dose-dependent and sex-related effects of 3 hepatocarcinogens were investigated by measuring the number and area of gamma-glutamyl transpeptidase (gamma-GT) positive foci appearing in the liver. For this, three different doses of 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and DL-ethionine (ethionine), respectively, were given to F344 rats of both sexes for 6 weeks after a single injection of diethylnitrosamine (DEN). The inductions of gamma-GT positive foci by 2-AAF and 3'-Me-DAB were clearly dose-dependent, but with 2-AAF this was clearer in males than females. Ethionine had less clear dose-dependent effects in both males and females. Under these conditions, the minimal effective doses of 2-AAF, 3'-Me-DAB and ethionine, respectively, were 0.0008%, 0.0024% and 0.05% in males and 0.004%, 0.012% and 0.05% in females. The results indicate that these 3 carcinogens had clear dose-dependent effects in the induction of gamma-GT positive foci when given for a short period in the promotive stage and that male rats were more susceptible than females to 2-AAF.

2-Acetylaminofluorene↗
PubMed1983

Transplacental effect of N-diethylnitrosamine on chromosomal aberrations in fetal tracheal cells of the Syrian hamster: comparison between epithelial and mesenchymal cells.

Chromosomal aberrations were investigated in tracheal cells of fetal Syrian hamsters after transplacental administration of N-diethylnitrosamine (DEN). On the 15th day of pregnancy, Syrian hamsters were injected s.c. with a tumorigenic dose of DEN (50, 100 and 200 mg/kg body weight). Two hours later, the fetal tracheae were isolated, the epithelial tissue was separated from the mesenchymal tissue by collagenase-treatment, and then each cell population was transferred to cell culture after Dispase treatment. At 24, 48 and 72 h after the cell cultivation, chromosomal damage was examined. The results clearly showed that a high incidence of chromosomal aberrations, especially chromatid-type exchanges, was seen in the epithelial cells of DEN-treated groups. However, significant induction of chromosomal aberrations was not observed in the mesenchymal cells from DEN-treated groups.

Animals↗
PubMed1983

Survey of various chemicals for initiating and promoting activities in a short-term in vivo system based on generation of hyperplastic liver nodules in rats.

The effects of pre- (initiation stage) and post- (promotion stage) administration of 17 chemical carcinogens (including both hepatic and non-hepatic carcinogens), 3 promoters and 2 non-carcinogenic analogs, on the induction of liver hyperplastic nodules were investigated in rats. Test chemicals were administered during the initiation stage after which rats were fed dietary N-2-fluorenylacetamide (2-FAA) for 2 weeks in conjugation with necrogenic CCl4 to enhance production of nodules initiated by test chemicals. Alternatively, effects of test chemicals administered during the promotion phase were evaluated in rats given a combination of dietary 2-FAA for 2 weeks and necrogenic CCl4. This initiation regimen resulted in very few nodules unless a promoter was subsequently used. All chemical carcinogens administered during the initiation stage induced more frequent, larger hyperplastic nodules than did control treatments. However, neither the promoters nor the non-carcinogenic analogs induced hyperplastic nodules if they were administered during the initiation stage. In contrast, hepatocarcinogens and a promoter of hepatocarcinogenesis (phenobarbital) administered in the promotion stage had enhancing (promoting) activity on hyperplastic liver nodules, whereas non-hepatocarcinogens, a promoter for skin carcinogenesis (12-O-tetradecanoylphorbol-13-acetate) and a promoter for urinary bladder carcinogenesis (saccharin) did not. Non-carcinogenic analogs were not active when administered during either the initiation or promotion stages. These findings demonstrated the utility of employing short-term in vivo assays for both initiating and enhancing (promoting) activities of chemicals. By our system, chemicals were classified into 4 main groups, namely, (i) hepatocarcinogens which have both initiating and enhancing activity, (ii) non-hepatocarcinogens with initiating activity only, (iii) promoters of hepatocarcinogenesis which have promoting activity and (iv) non-carcinogens and non liver promoters which did not initiate nor promote nodule development. This is a more discriminating means of assaying carcinogenic activity than is possible with short-term in vitro screening assays for mutagenicity.

Animals↗
PubMed1983

Sequential observations on the appearance of neoplastic lesions in the liver and kidney after treatment with N-ethyl-N-hydroxyethylnitrosamine followed by partial hepatectomy and unilateral nephrectomy.

Sequential observations were carried out on the induction of preneoplastic lesions in the liver and the kidney. Rats were initially given N-ethyl-N-hydroxyethylnitrosamine (EHEN) in their drinking water (0.1%) for 3 days (Group 1), 1 week (Group 2) or 2 weeks (Group 3) or tap water (Group 4). Rats in Groups 1-3 were subjected to partial hepatectomy and unilateral nephrectomy (right side) 2 weeks after the end of EHEN treatment. Rats from these groups were killed in week 10, 20, 30 and 40 of the experiment. In the liver, the effect of EHEN in the induction of gamma-glutamyltranspeptidase (gamma-GT) positive foci and hyperplastic nodules (HN) was clearly dependent on the length of treatment. The preneoplastic lesions increased with the lapse of observation time. Changes measured as number of gamma-GT positive foci were 10-40 times greater than those measured as HN, especially among the small size range. Values for changes in Group 1 given 0.1% EHEN for 3 days were very low, indicating that this dose is close to the threshold. Two rats with hepatocellular carcinoma in Group 3 given EHEN for 2 weeks survived until week 40. In the kidney, tubular epithelial proliferations composed of cells with slightly basophilic cytoplasm and slightly atypical nuclei were tentatively named atypical cell foci (ACF). EHEN induced ACF, renal cell adenomas and renal cell carcinomas. The increase in the induction of ACF was dependent on the length of observation period but not on the length of treatment. Even though control rats (not treated with EHEN) also had ACF, their quantitative values were far less than the groups given EHEN and killed at week 40, indicating that a large number of ACF were induced by EHEN. Therefore, EHEN is good for experimental induction of preneoplastic lesions in the liver and kidney of rats. The experimental schedule for Groups 1 and 2 could be used as a shortterm screening test for promoters and the schedule for Group 3 as an assay for inhibitors.

Animals↗
PubMed1983

Molecular forms of glutathione S-transferase and UDP-glucuronyltransferase as hepatic preneoplastic marker enzymes.

Changes in molecular forms of glutathione S-transferase (GST) and UDP-glucuronyltransferase (UDP-GT) as hepatic detoxicating enzymes were investigated during chemical hepatocarcinogenesis in the rat. The activity and the protein amount (formula; see text) itself of the GST-A form, which has fetal characteristics and is separable from other forms by CM-Sephadex column chromatography and by immunologic techniques, was much increased in gamma-glutamyl transpeptidase (gamma-GTP)-positive foci or hyperplastic nodules (HNs) induced by diethylnitrosamine and 2-fluorenylacetamide or 3'-methyl-4-dimethylaminoazobenzene. The activity of enzyme 1 (late fetal form) of UDP-GT assayed with o-aminophenol (o-GT) also increased with increased number of the foci or HNs, while the activity of enzyme 2 (neonatal form) assayed with phenolphthalein (p-GT) changed but little. The foci and HNs were stained more strongly than the nonnodular areas immunohistochemically using the antibody against purified GST-A or o-GT. The two activities were also increased in well-differentiated hepatomas, but they were decreased in moderately and poorly differentiated hepatomas, and activating enzymes such as cytochrome P-450 were markedly decreased from HN. GST-A and o-GT differ from fetal enzymes such as those of carbohydrate metabolism in that they are inducible in the short-term by drugs, including carcinogens, and they show the highest activities in HNs, and so they may be considered as hepatic preneoplastic (PN) antigens.

Animals↗
PubMed1983

Severe combined immunodeficiency in a child with a healthy adenosine deaminase deficient mother.

We investigated adenosine deaminase (ADA) deficient severe-combined immunodeficiency (SCID) in an 8-month-old child with ADA deficient mother. The ADA deficiency in the child was unusual in that the thymic histology was normal. In addition, the thymocytes formed E-rosettes with sheep erythrocytes and were stimulated by T-cell mitogens. ADA activity could not be detected in the child's thymocytes. Studies on the family indicated that the father had about one-half of the normal erythrocyte ADA activity. All the family members with detectable ADA activity appeared to have, according to starch gel electrophoresis of erythrocyte lysates, the common ADA-1 phenotype; however, rigorous identification of phenotype was not possible in this study. The mother had less than 1% of normal ADA activity in both erythrocyte and lymphocyte extracts, but her whole peripheral blood lymphocytes demonstrated about 6% of normal activity. Normal concentrations of ATP and small amounts of dATP were found in the mother's erythrocytes. Deoxyadenosine excretion in her urine was elevated and approximately 5-10% of that excreted by individuals with ADA deficient SCID. These studies suggest that low amounts of ADA activity in erythrocytes and blood lymphocytes of certain individuals may be compatible with good immune function and longevity.

Adenosine Deaminase↗
PubMed1983

Separation of human colostral macrophages and neutrophils on gelatin and collagen-serum substrata.

A new technique for separation of human colostral macrophages and neutrophils was developed. Macrophages attached more readily to acid soluble collagen-serum or gelatin-serum substrata than neutrophils. Most of the adherent neutrophils were removed during the first 5 minutes incubation in 3 mM EDTA, thereafter, complete detachment of macrophages followed. Neutrophils and macrophages were enriched more than 80% in nonadherent cell populations and detached cell populations, respectively. These separated colostral leukocytes retained their viability and phagocytic activities. Therefore, functional studies of these purified human colostral leukocytes are possible.

Cell Adhesion↗
PubMed1983

Comparison of the promoting effects of various agents in induction of preneoplastic lesions in rat liver.

The promoting activities of 29 compounds on induction of hyperplastic (neoplastic) liver nodules (HN) and the dose-dependent effects of tumor promoting agents were compared by using a short-term test system developed in this laboratory. In tests on promoting activity, F344 rats were given a single dose (200 mg/kg) of N-nitrosodiethylamine (DEN), and from two weeks later, were treated with various test compounds for 6 or 10 weeks. They were subjected to partial hepatectomy 3 or 4 weeks after DEN treatment. The results showed that strong hepatocarcinogens, such as aflatoxin B1, DEN, N-nitrosodimethylamine (DMN), 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and ethionine, induced many hyperplastic liver nodules, whereas dieldrin, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), polychlorinated biphenyls (PCB) and alpha-hexachlorocyclohexane (alpha-HCH) induced few lesions. Nonhepatocarcinogens, such as N-nitrosoethylurea (ENU) and 3-methylcholanthrene (3-MC), only slightly induced hyperplastic nodules. Of the miscellaneous compounds tested, phenobarbital, deoxycholic acid and ethynyl estradiol also induced gamma-glutamyl transpeptidase (gamma-GT) positive foci. In tests on the dose-dependent effects of promoting agents, DMN was given at different concentrations for 6 weeks from 2 weeks after DEN treatment. Results were quantitated by histochemical measurement of the number or area of gamma-GT positive lesions induced. A long-term experiment on the effect of feeding DMN for 96 weeks was also done. Clear dose-dependent effects of DMN were seen in induction of gamma-GT positive foci in the short-term experiment and neoplastic lesions in the long-term one.

2-Acetylaminofluorene↗
PubMed1983

Promotion of liver cancer development by brief exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or carbon tetrachloride.

Adult male Fischer rats were exposed to a necrogenic dose (200 mg/kg) of diethylnitrosamine or to nonnecrogenic doses of N-methyl-N-nitrosourea, 1,2-dimethylhydrazine, or benzo(a)pyrene following partial hepatectomy or sham hepatectomy. This treatment by itself led to no hepatocellular carcinomas by 8 to 18 months, except in animals given N-methyl-N-nitrosourea, which showed a 30% incidence by 12 months. With each treatment regimen, exposure to dietary 2-acetylaminofluorene for 2 weeks coupled with partial hepatectomy or the administration of a necrogenic dose of CCl4, was associated with an incidence of 68 to 94% of cancer at 8, 12, or 18 months, depending upon the initiating carcinogen used. Appropriate controls showed either no hepatocellular carcinoma or a much lower incidence. It is concluded that the 2-week exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or the administration of CCl4 has a strong promoting effect on liver carcinogenesis with four different chemical carcinogens.

1,2-Dimethylhydrazine↗