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Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 577 records · Page 32Linked to original sources
PubMed1984

Unusual clinical courses of adult T-cell leukemia in siblings.

Two siblings who developed adult T-cell leukemia (ATL) with unusual clinical courses are presented. The brother showed spontaneous remissions at the beginning stage of the disease of 6 years' duration, and the sister remains free of complaints for 6 years without chemotherapy. The patients and 2 of 12 healthy members of their family examined had serum antibodies against ATL-associated antigens (ATLA). The expression of ATLA was observed in the cultured lymphocytes from the patients and one of the family members.

Antibodies, Monoclonal↗
PubMed1984

Comparative light and scanning electron microscopic observations of nasal cavity carcinogenesis in rats treated with 1,4-dinitrosopiperazine.

Epithelial lesions in the nasal cavity of male F344 rats appeared as papillary and nodular hyperplasias progressing to invasive carcinomas during administration of 1,4-dinitrosopepirazine (DNP) at a dose of 0.01% in the drinking water. Observations with specific attention to the cells covering the luminal surface of the mucosa were made by scanning electron microscopy at 10-week intervals. After administration of DNP for 20 and 30 weeks three different types of light microscopically identifiable focal lesions, i.e., papillary hyperplasia, nodular hyperplasia and papilloma, of the epithelium in the nasal cavity were distinguished, and after 40 and 50 weeks areas of squamous cell carcinomas were also observed. In the scanning electron microscope, papillary hyperplasia appeared as a nodular elevation of the surface with a smoother appearance than the surrounding nonnodular areas. Areas of nodular (inverted) hyperplasias had irregularly shaped indentions of the surface. Papillomas appeared as pedunculated projections of the surface. Carcinoma presented as a protrusion of irregular cell masses. The surface cells in the areas of papillary and nodular hyperplasias and of papilloma had numerous short microvilli rather uniform in shape (short-uniform microvilli), unlike the normal epithelium in the nasal cavity, which possesses cilia or olfactory vesicles. The microvilli of carcinoma cells were more irregular in shape and size than those of hyperplastic cells (pleomorphic microvilli).

Animals↗
PubMed1984

Modification of N-methyl-N-nitrosourea initiated carcinogenesis in the rat by subsequent treatment with antioxidants, phenobarbital and ethinyl estradiol.

The modifying effects of butylated hydroxyanisole (BHA), sodium L-ascorbate (SA), phenobarbital (PB) and ethinyl estradiol (EE) were studied by their administration to F344 rats subsequent to initiation with N-methyl-N-nitrosourea (MNU), a wide-spectrum carcinogen inducing tumors in many organs. Rats were initially given 4 doses of MNU (50 mg/kg) intraperitoneally within a 2-week period and then placed on a diet containing BHA (1%), SA (5%), PB (0.05%) or EE (0.001%) for 23 weeks prior to killing. Since the experiment was based on a whole body concept of carcinogenesis, all major organs were examined histologically and histochemically for any preneoplastic lesions. BHA enhanced forestomach and urinary bladder carcinogenesis as did SA also for the urinary bladder, whereas PB enhanced the induction of gamma-glutamyl transpeptidase positive (gamma-GT+) foci in the liver and also the incidence of thyroid carcinoma and forestomach carcinoma. In contrast, EE inhibited the induction of thyroid tumors, malignant lymphoma or leukemia. Thus these compounds, when given after initiation of many organs by a single carcinogen, exert an influence on the site of tumor development by, as yet unknown, organotropic modifying effects.

Animals↗
PubMed1984

Enhancement of phenotypic instability by alpha-difluoromethylornithine and butylated hydroxyanisole in rapidly induced rat liver lesions.

The effects of alpha-difluoromethylornithine (DFMO), butylated hydroxyanisole (BHA), sodium phenobarbital (PB) and 2-acetylaminofluorene (AAF) administration on the further development of rat liver nodular lesions induced in a short-term system were investigated. The results clearly demonstrated an association between DFMO and BHA treatment with reduction in numbers of persisting nodules as assayed histopathologically and by analysis of gamma-glutamyltranspeptidase (gamma GT) and glucose-6-phosphate dehydrogenase (G6PDH) positive populations. PB and to a lesser extent AAF, on the other hand, appeared to exert an opposite effect, apparently enhancing the phenotypic stability of the nodular putative preneoplastic lesions.

2-Acetylaminofluorene↗
PubMed1984

Caffeine inhibition of the metabolic activation of a carcinogen, 4-nitroquinoline-1-oxide, in cultured Chinese hamster cells.

The cytotoxic effect of 4-nitroquinoline-1-oxide (4NQO) on cultured Chinese hamster cells was drastically reduced by the presence of caffeine (0.2-1 mM). Caffeine, however, did not reduce the cytotoxicity of 4-hydroxyaminoquinoline-1-oxide (4HAQO), an active metabolite of 4NQO. The 105 000 g supernatant from the cell homogenate could catalyze the conversion of 4NQO to 4HAQO in the presence of NADPH or NADH as a hydrogen donor. This enzyme activity was strongly inhibited by caffeine (0.1-10 mM) or dicumarol (10(-8)-10(-6) M), an inhibitor of DT diaphorase (E.C.1.6.99.2). Dicumarol also reduced the cytotoxicity of 4NQO. These results clearly suggest that caffeine inhibits the conversion step of 4NQO to 4HAQO, resulting in a decrease in the cytotoxicity of 4NQO. Furthermore, the frequency of 6-thioguanine-resistant mutation by 4NQO was also strongly reduced by the presence of caffeine (1 mM) in cultured Chinese hamster cells, being consistent with the results of cytotoxicity.

4-Nitroquinoline-1-oxide↗
PubMed1984

Induction by butylated hydroxyanisole of specific molecular forms of glutathione S-transferase and UDP-glucuronyltransferase and inhibition of development of gamma-glutamyl transpeptidase-positive foci in rat liver.

Effects of an antioxidant, butylated (3-tert-butyl-4-) hydroxyanisole (BHA) on the induction of specific molecular forms of glutathione S-transferase (GST), UDP-glucuronyltransferase (UDP-GT) and other glutathione-related enzymes in rat liver were investigated. The development of gamma-glutamyl transpeptidase (gamma-GTP)-positive foci and hyperplastic nodules induced by diethylnitrosamine, 200 mg/kg i.p., followed by 0.02% N-2-fluorenylacetamide (FAA) in diet plus partial hepatectomy was inhibited by the administration of 0.75% BHA in the FAA-containing diet. Inhibition was reflected in decreased area of gamma-GTP-positive foci which correlated with a decrease in gamma-GTP activity measured biochemically. Under the present experimental conditions, total activities of GSTs, especially that of GST-A form, and of UDP-GTs, especially that of the late fetal form (o-GT), were markedly increased, together with glutathione levels in the whole liver, within one week after BHA administration. Without BHA administration the activities of GST-A and o-GT, as well as glutathione levels, were also increased by FAA treatment, primarily localized within gamma-GTP-positive foci. These results suggest that the induction of specific molecular forms of detoxicating enzymes either in enzyme-altered foci or in the whole liver may play an important role in determining the extent of development of preneoplastic nodules from initiated foci under the short term induction conditions used.

Animals↗
PubMed1984

Modifying effects of butylated hydroxyanisole, ethoxyquin and acetaminophen on induction of neoplastic lesions in rat liver and kidney initiated by N-ethyl-N-hydroxyethylnitrosamine.

Studies were made on the effects of butylated hydroxyanisole (BHA), ethoxyquin (EQ) and acetaminophen (AAP) on the induction of neoplastic lesions in the liver and kidney of rats initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN). The number and area of histochemical gamma-glutamyltranspeptidase-positive (gamma-GT+) foci per unit area of liver section in rats given BHA, EQ or AAP were significantly less than in rats given EHEN alone. Similarly, the number of hyperplastic nodules (HN) in groups given BHA or AAP and their area in groups given BHA, EQ or AAP were significantly less than in control groups. Induction of hepatocellular carcinoma (HCC) was also clearly inhibited by these three chemicals. No liver lesions were found in any animals given BHA, EQ or AAP orally without EHEN. In contrast, the incidence and quantitative values of preneoplastic lesions and renal cell adenoma were significantly increased in groups given BHA, EQ or AAP. The results clearly demonstrated that BHA, EQ and AAP inhibited the development of gamma-GT+ foci, HN and HCC, whereas they enhanced the appearance of preneoplastic and neoplastic lesions in the kidney.

Acetaminophen↗
PubMed1984

Oxygen metabolism of human colostral macrophages: comparison with monocytes and polymorphonuclear leukocytes.

Human colostral macrophages stimulated by opsonized zymosan or phorbol myristate acetate (PMA) released superoxide anions (O2-) and hydrogen peroxide (H2O2) with activities comparable to those of monocytes and about one-fourth of those of polymorphonuclear leukocytes (PMNL) of blood. The O2- -forming oxidase in the macrophages stimulated by PMA was dependent on NADPH as an electron donor with an apparent Km value for NADPH of 27.6 +/- 4.0 microM, which is comparable to those obtained for the stimulated monocytes and PMNL of blood. The Vmax was 1.86 +/- 0.33 nmol O2/min/10(6) cells, which is essentially the same as that of monocytes and about half of that of PMNL. p-Chloromercuribenzoate or cetyltrimethylammonium bromide completely inhibited oxidases of all three types of phagocytes. A b-type cytochrome was identified in the macrophages but the concentrations in the macrophages and monocytes were less than half of that in PMNL. These results suggest that the differences in the O2- -forming activities of the three types of phagocytes are quantitative rather than qualitative. The macrophages and monocytes showed very low activities of myeloperoxidase [EC 1.11.1.7] in contrast to PMNL. The activity of beta-glucuronidase [EC 3.2.1.31] in the macrophages was much higher than those of the monocytes and PMNL, but little difference was observed in the activities of lysozyme [EC 3.2.1.17], catalase [EC 1.11.1.6] and superoxide dismutase [EC 1.15.1.1] among the three types of phagocytes examined. Electron micrographs of the macrophages showed little increase of vacuoles upon exposure to PMA, in contrast to the cases of monocytes and PMNL.

Catalase↗
PubMed1984

Three-dimensional observations by scanning electron microscopy on the blood supply and organization of vasculature during hepatocarcinogenesis in rats.

Three-dimensional vascular changes in rats during hepatocarcinogenesis were studied by stereoscopic and scanning electron microscopic observation of vascular casts of sinusoids by injecting resin from hepatic artery (red color) and portal vein (blue color). Neoplastic lesions were synchronously induced by injection of diethylnitrosamine (DENA) followed by feeding of 2-acetylaminofluorene (2-AAF) plus partial hepatectomy, then periodically killed for examination. At 6 weeks after DENA injection sinusoids of hyperplastic foci (HF) were filled with blue resin similar to surrounding tissue, then at 8 weeks some HF and hyperplastic nodules (HN) took up red resin leaving surrounding sinusoids blue. At 12 to 18 weeks, red HN became more discrete with obvious compression of surroundings but decreased their number whereas blue HN were not. Red HN had incomplete anastomosing sinusoids giving a coral-like appearance. Spongy or cystic areas contained little or no resin, suggesting ischemic condition. Hepatocellular carcinomas (HCC) at 40 weeks took exclusively arterial red resin forming irregularly shaped anastomosing sinusoids. These findings indicate that acquisition of arterial blood supply by HF may relate to their further development to persistent HN and HCC.

2-Acetylaminofluorene↗
PubMed1984

Modification of carcinogenesis by antioxidants and other compounds.

Studies were made on the effects of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium L-ascorbate (SA), ethoxyquin (EQ) and acetaminophen (AAF) on the induction of neoplastic lesions in the liver, kidney or urinary bladder of rats initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN), diethylnitrosamine (DEN) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The number and area of histochemical gamma-glutamyltranspeptidase-positive (gamma-GT+) foci per unit area of liver section in rats given BHA, BHT, EQ or AAP, but not SA, were significantly less than in rats given EHEN or DEN alone. Similarly, the number of hyperplastic nodules (HN) in groups given BHA or AAP and their area in groups given BHA, EQ or AAP were significantly less than in control groups. Induction of hepatocellular carcinoma (HCC) was also clearly inhibited by these three chemicals. In contrast, the incidence and quantitative values of preneoplastic lesions and renal cell adenoma in the group given EHEN were significantly increased in groups given BHA, EQ or AAP administration. For assesing the influence of BHA and BHT on urinary bladder carcinogenesis, rats received BHA or BHT after treatment with BBN. The incidences and the number per unit length of basement membrane of papilloma and carcinomas were significantly increased in rats given BHA. BHT also showed significant increase but values were less than with BHA. These results clearly demonstrated that BHA, BHT, EQ and AAP inhibit the development of gamma-GT+ foci, or HN and HCC, whereas BHA, EQ and AAP enhance the appearance of preneoplastic and neoplastic lesions in the kidney, BHA and BHT also enhancing urinary bladder carcinogenesis.

Acetaminophen↗
PubMed1984

Effects of margarine on hepatocarcinogenesis by N,N'-2, 7-fluorenylenebisacetamide in mice.

The effect of a safflower margarine on hepatocarcinogenesis by N,N'-2, 7-fluorenylenebisacetamide was compared with that of safflower oil from which the margarine was made. A high-dextrin diet was used as a control for the two high-fat diets. The number of surviving mice in the margarine group at the end of the experiment was significantly lower compared with both the dextrin and the oil groups. A significantly high incidence of hepatic nodules type 2 was observed in the margarine group, whereas most liver tumors in both the dextrin and the safflower oil groups were of HN type 1 (p less than 0.05). Hepatocellular carcinomas were induced in some mice in all the groups. However, no statistical difference was found among the three dietary groups. Thus the difference in the types of the hepatic nodules among the three groups was not reflected in the incidence of hepatocellular carcinoma.

2-Acetylaminofluorene↗
PubMed1984

Promotive effect of primary and secondary bile acids on the induction of gamma-glutamyl transpeptidase-positive liver cell foci as a possible endogenous factor for hepatocarcinogenesis in rats.

The promoting effects of 5 bile acids on liver carcinogenesis were investigated in male Fischer rats initially treated with diethylnitrosamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given bile acids for 8 weeks. At 3 weeks following DEN administration, all rats were subjected to partial hepatectomy. Among the bile acids tested, cholic acid (CA) and deoxycholic acid (DCA) exerted promoting activity as evidenced by significantly increased values of gamma-glutamyl transpeptidase-positive (gamma-GT+) foci as compared with the corresponding controls given DEN alone. In contrast, the other 3 bile acids tested, chenodeoxycholic acid (CDCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA), did not significantly increase the level of gamma-GT+ foci over that induced by DEN alone. It is noteworthy that only bile acids of the same metabolic pathway, CA as a primary bile acid and DCA as a secondary bile acid, showed promoting effects whereas CDCA and its metabolic derivatives, LCA and UDCA, were inactive. The results indicate that CA and DCA might act as endogenous promoters of hepatocarcinogenesis in pathological conditions with increased levels of serum bile acids.

Animals↗
PubMed1984

Modifying potential of thirty-one chemicals on the short-term development of gamma-glutamyl transpeptidase-positive foci in diethylnitrosamine-initiated rat liver.

The modifying potential of 31 different compounds on the development of gamma-glutamyl transpeptidase-positive (gamma-GT+) liver cell lesions was compared in an in vivo short-term assay system. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine intraperitoneally and 2 weeks later were treated with test compounds for 6 weeks and then sacrificed, all rats being subjected to partial hepatectomy at week 3. Modifying potential was scored by comparing the number and area (mm2)/cm2 of induced gamma-GT+ foci with those of the corresponding control group given DEN alone. 2-Acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, dimethylnitrosamine, phenobarbital, barbital, dipyrone and deoxycholic acid caused a significant enhancement of both the number and area of foci. 4-Acetylaminofluorene, ethionine, benzo[alpha]pyrene, disulfiram and cholic acid had a moderate enhancing effect, whereas slight, but not unequivocal, increases in gamma-GT+ foci were observed after captafol, glutathione, sodium ascorbate and taurine administration. In contrast, acetaminophen, ethoxyquin, butylated hydroxyanisole, butylated hydroxytoluene, and ethyl alcohol showed clear inhibitory effects. It is concluded that the present short-term in vivo system has practical application for the screening of modifying agents for liver tumorigenesis including hepatocarcinogens.

Animals↗
PubMed1984

Clinical aspects of adult T-cell leukemia/lymphoma (ATL).

We screened serum samples from patients with various hematological disorders and healthy individuals for the presence of adult T-cell leukemia/lymphoma associated antigen (anti-ATLA) antibodies. These antibodies were detected not only in all patients with ATL but frequently in those diagnosed as T-cell malignant lymphoma or T-cell chronic lymphocytic leukemia; the positivity rate of anti-ATLA antibody was lower in B- and null-cell-type lymphoma, B-cell chronic lymphocytic leukemia, and multiple myeloma. Patients with aplastic anemia or acute leukemia who had received frequent and massive blood transfusions also possessed anti-ATLA antibodies. About 5.5% of the healthy individuals over 40 years of age in the endemic area (Kumamoto) were carriers. The rate of positivity gradually increased with age, and was higher in females than in males. In addition, the peripheral blood mono-nuclear cells and/or lymph node cells from patients with various hematological disorders, including ATL, were examined. The presence of human T-cell leukemia/lymphoma virus type I (HTLV-I) proviral DNA was confirmed in all patients with ATL and in some with T-cell-type malignant lymphomas. However, in HTLV-I carriers or other patients with hematological disorders without ATL, proviral DNA was not detected. In endemic areas, detection of proviral DNA is essential for the classification and diagnosis of T-cell malignancies.

Adolescent↗