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Biomedical subjects

H Sugano

Publications and source records attributed to H Sugano.

At least 73 records · Page 4Linked to original sources
PubMed1990

Development of transgenic mice containing woodchuck hepatitis virus DNA.

We produced transgenic mice containing woodchuck hepatitis virus DNA with tandem repeat structure capable of producing virus and viral antigens. Poly(A)+ RNAs probably corresponding to pregenome and viral antigens were detected in their liver. These mice have now been healthy for one year. However, there is the possibility of inducing immunologically mediated hepatitis. We anticipate these transgenic mice may present a useful model system for studying the significance of chronic hepatitis in hepatocellular carcinoma development.

Animals↗
PubMed1990

Synthesis and central nervous system actions of thyrotropin-releasing hormone analogues containing a dihydroorotic acid moiety.

A series of thyrotropin-releasing hormone (TRH) analogues in which the pyroglutamic acid residue was replaced by (S)-4,5-dihydroorotic acid (Dio-OH) and the related derivatives were prepared. Their central nervous system actions based on spontaneous locomotor activity, antagonistic effect on reserpine-induced hypothermia, and antagonistic effect on pentobarbital anesthesia were evaluated and the structure-activity relationships are discussed. Of these, (1-methyl-(S)-4,5-dihydroorotyl)-L-histidyl-L-prolinamide (14b) showed the most potent activities, which were 30-90 times greater than those of TRH. Moreover, the thyrotropin-releasing activity of 14b was about 50 times weaker than that of TRH, and compound 14b (TA-0910) was selected as a potent candidate.

Anesthesia↗
PubMed1990

Red and blue distinctive mucin-histochemical types of Japanese colorectal mucosa.

Mucin-histochemical characteristics of normal human colorectal mucosa were investigated utilizing Culling et al.'s staining method which distinguishes the mode of C8-O-acylation of sialomucins. Normal mucosae of cecum, ascending, transverse and descending colon and rectum were obtained from autopsy and biopsy material. Japanese colorectal mucosa stained either entirely red or entirely blue, in contrast to previous reports dealing with Caucasians where all the normal mucosa reportedly stained red. The ratio of red to blue colon cases varied to some extent with age, i.e. it was found to be 1:1 in children aged 0 to 4, 2:1 in the 5-20 age group, and 4:1 in people older than 21 years, suggesting a tendency of shift from blue to red during early life in Japan. Each individual Japanese adult colorectal mucosa may thus be classified into either red or blue type mucin-histochemically.

Adolescent↗
PubMed1990

A statistical analysis of lung cancer registered in the Annual of Pathological Autopsy Cases in Japan between 1958 and 1987, with special reference to the characteristics of lung cancer in Japan.

Autopsy cases of lung cancer, 41,988 in males and 13,818 in females, consecutively registered between 1958 and 1987, were analysed statistically and compared with other case materials and mortality statistics. Cases of malignant tumor showed a gradual increase, and now comprise 60% of the total male and 55% of the total female autopsy cases. The percentage of lung cancer cases among the total autopsy cases was 9% for males and 5% for females. The percentage of lung cancer cases among total cases of malignant tumor was about 17% for males and 9% for females. Among fatal malignant tumors, gastric cancer and lung cancer showed the highest frequency. The relative incidence of gastric cancer was seen to decrease, whereas that of lung cancer increased. Of the histological types of lung cancer in both sexes, adenocarcinoma was the most frequent, followed by squamous cell carcinoma. During the period studied the peak age of patients with lung cancer shifted from the seventh to eighth decade, and a significant elevation of mean age was demonstrated for all of the major histological types in both sexes. The male:female ratio for all lung cancer cases was 3.0, which was much lower than those for the United States and Europe, but very similar to the ratios of mortality statistics in Japan and other Asian countries. As a result of a previous autopsy study at the University of Tokyo, it was also confirmed that the male:female ratio relative to age in each country reflects very well the histological distribution.

Adenocarcinoma↗
PubMed1990

[Study of breast cancers during pregnancy and lactation].

From breast cancer cases that were mastectomized between 1970 and 1987 at the Cancer Institute Hospital, 43 breast cancers during phases of pregnancy and lactation (pregnancy 11 cases, lactation 32 cases) have been analyzed. Taking the patient's age and the calendar-year at the time of diagnosis into account, we collected 43 cases as controls and compared the result. It was found that breast cancers during pregnancy and lactation metastasized to the lymph nodes at the same frequency as in the control cases, in lymph node-positive cases and in tumors of the same size the metastases involved more lymph nodes than in the control cases. Further, the survival rate of breast cancers during pregnancy and lactation was poorer in the lymph node-positive cases than in the controls. Therefore, we have concluded that pregnancy and lactation promote the progress of a metastatic cancer.

Adult↗
PubMed1990

[The relation of the DNA ploidy pattern to lymphatic permeation in pure-type diffuse infiltrative carcinomas of the stomach].

Lymphatic permeation (ly) is considered an important prognostic factor, even in the case of a diffuse infiltrative carcinoma (DICA) of the stomach, which generally has the poorest prognosis among the various types of gastric carcinomas. Our previous study has revealed that the ly in DICA is strongly related to the histological type of carcinoma that infiltrates the tumor tissue: the "mixed type", i.e., a type that includes tubular/trabeculoacinar element in 10% or more of the tumor tissue presents a significantly higher incidence of ly than the "pure type", i.e., a type that consists almost exclusively of anaplastic/mucocellular carcinoma. However, even in the "pure type" cases, some show a high ly incidence. To clarify this discrepancy, the DNA ploidy pattern in the "pure type" DICA was investigated, since the DNA ploidy has been reported to correlate well with the invasiveness or the metastatic tendency of the tumor. Although most of the cases (70%) showed a heteroploidy, such an incidence was significantly higher in the cases with a marked ly (86%) than in the cases without ly. (60%). As a result, we have concluded that in cases of a DICA, the lymphatic permeation (ly) is remarkably influenced not only by the histological type seen but also by the DNA ploidy pattern of the carcinoma.

DNA, Neoplasm↗
PubMed1989

Ceramic hydroxyapatite high-performance liquid chromatography of complexes membrane protein and sodium dodecylsulfate.

Ceramic hydroxyapatite high-performance liquid chromatography was examined as a chromatographic method by which complexes of whole membrane proteins and sodium dodecyl sulfate could be analyzed. The chromatographic conditions were optimized using the erythrocyte membrane as a model. Whole proteins, including membrane proteins larger than 100 kDa, were eluted as sharp peaks from the column and separated well from each other under optimum conditions. This method gave better resolution of protein-SDS complexes than other chromatographic methods reported so far. The sodium dodecyl sulfate complexes of 24 well characterized proteins were analyzed by this method and their retention times were examined. The positive correlation of the retention time with log (molecular mass) and log sigma (hydrophobicity of amino acids) but not with the isoelectric point, was observed. Based on these results, the mechanism underlying the interaction of protein-SDS complexes with ceramic hydroxyapatite was discussed.

Animals↗
PubMed1989

Pulmonary sclerosing hemangioma of the lung. A type II pneumocytoma by immunohistochemical and immunoelectron microscopic studies.

Three cases of pulmonary sclerosing hemangioma were studied by immunohistochemical and immunoelectron microscopic methods using a panel of antibodies. Six cases of adenocarcinoma of the lung, three cases of normal mesothelium, and three cases of mesothelioma were used as controls. The cytoplasm of some of the sclerosing hemangioma tumor cells was positive for the anti-lung surfactant apoprotein monoclonal antibody (PE-10). These cells were the pale cells of the solid areas, the cells covering the papillary projections, and the cells lining the cleft-like spaces. These cells also were positive for conventional epithelial cell markers. Some cells also were positive for vimentin. Electron microscopic study showed that the predominant cell was a poorly differentiated pneumocyte. Immunoelectron microscopic study also demonstrated that PE-10 existed in the rough endoplasmic reticulum of some of the cells in the solid areas, in the same way as normal type II pneumocytes. We concluded that the sclerosing hemangioma is an epithelial tumor with differentiation towards type II pneumocytes.

Aged↗
PubMed1989

Purification of heat shock protein 90 from calf uterus and rat liver and characterization of the highly hydrophobic region.

Heat shock protein 90 was purified from calf uterus and rat liver. Both heat shock protein 90s had similar molecular weights, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, of Mr 87,000 and 88,000, isoelectric points of 5.2, and Stokes radii of 6.7 and 6.5 nm, respectively. Heat shock protein 90 bound to phenyl-Sepharose CL-4B even at low ionic strength, and also bound to butyl-Toyopearl at high ionic strength. Heat shock protein 90 bound to phenyl-Sepharose could be eluted with a buffer containing organic solvents or detergents such as 2-propanol, dioxane, dimethylformamide, methyl cellosolve, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate or Triton X-100, but not with ionic salts such as 1 M KCl. These results suggest that heat shock protein 90 possesses a significant hydrophobic region on the surface of the molecule. Hydrophobicities of heat shock protein 90 and 4S calf uterine estrogen receptor were both decreased by formation of a 8 S estrogen receptor complex. The role of the hydrophobic region of heat shock protein 90 in the interaction with estrogen receptor and other proteins is discussed.

Animals↗
PubMed1989

Differential effects of methylmercury on the synthesis of protein species in dorsal root ganglia of the rat.

Dorsal root ganglia from control and methylmercury (MeHg)-treated rats were incubated in vitro with 35S-methionine ant the proteins synthesized were analyzed by two-dimensional electrophoresis. The double labelling method, in which proteins of control dorsal root ganglia labelled in vitro with 3H-leucine were added to each of the two samples as an internal standard, was used to minimize unavoidable errors arising from the resolving procedure itself. The results obtained showed that the effect of MeHg on the synthesis of proteins in dorsal root ganglia was not uniform for individual protein species in the latent period of MeHg intoxication. Among 200 protein species investigated, 157 showed inhibition of synthesis close to that of the total proteins in the tissue (68% of the control). Among the remaining protein species, 20 showed real stimulation of synthesis, whereas 7 were moderately inhibited and 16 were inhibited more strongly than the total proteins in the tissue. These results suggest that the effect of MeHg on the synthetic rates for protein species in dorsal root ganglia differs with the species, and that unusual elevation or reduction of the synthesis of some protein species caused by MeHg may lead to impairment of normal nerve functions.

Animals↗
PubMed1989

Instability of integrated hepatitis B virus DNA with inverted repeat structure in a transgenic mouse.

We established four cell lines, from the liver cells of a transgenic mouse, constructed with hepatitis B virus DNA that had an inverted repeat structure. The integrated DNA patterns of the four established cell lines were different from one another and from the original pattern. These data show that the instability of integrated hepatitis B virus DNA would also occur in somatic cells during replication, apart from meiosis, which was previously reported.

Animals↗
PubMed1989

Enhanced O6-methylguanine-DNA methyltransferase activity in transgenic mice containing an integrated E. coli ada repair gene.

The E. coli ada gene encodes O6-methylguanine DNA methyltransferase (O6MTase) which repairs the methylation of guanine at the O6 position in DNA. After recombination with a Chinese hamster metallothionein I gene promoter, the ada gene was microinjected into C3H/HeN mouse zygotes. Eventually, transgenic mice containing the ada fusion DNA were generated. The integrated ada DNA complex was transmitted to the progeny in a mode conforming to tandem integration at a single chromosome site, and homozygotes were also obtained from an inter-transgenic mouse cross. RNA transcripts of the chimeric ada gene were identified in the livers of these transgenic mice using dot and Northern blot analyses. O6MTase activity was increased in the liver of transgenic mice of line No. 708, and was more than 3 times the activity found in non-transgenic mice, especially in the transgenic homozygotes. The ada gene product was detected in the liver of a transgenic homozygote by immunoblot analysis. These transgenic mice have great potential for analysis of the role played by O6MTase in chemical carcinogenesis.

Animals↗
PubMed1989

Pigment cells and pigment cell tumors in fish.

The three basic pigment cell types found in poikilothermic vertebrates, melanocytes (melanin-producing cells), erythrophores (red or yellow pigment cells), and iridophores (iridescence-producing cells), are derived from neural crest. Neoplasms of pigment cells in fish are also of three phenotypes, melanomas (melanophoromas), erythrophoromas, and iridophoromas, showing the phenotypes of their corresponding normal pigment cells. These pigment cell tumors are among the most common types in bony fish and seem to be more common in fish than in mammals, including humans. Moreover, there are no mammalian neoplasms corresponding to erythrophoromas and iridophoromas in fish. The complexities in the nature and classification of pigment cell tumors in fish will be discussed on the basis of a survey of our collection of these tumors at the Cancer Institute. The etiology of pigment cell tumors in fish is obscure. In order to know whether activated oncogene is involved in the genesis of erythrophoromas in goldfish, the ras genes from normal and erythrophoroma cells were cloned and their nucleotide sequences were compared. The goldfish ras gene and human ras genes showed striking homology. However, no point mutation at the 12th codon was observed in ras genes isolated from erythrophoromas. Besides pigment cell tumors in fish, abnormal pigmentation or depigmentation in flounders associated with diseased conditions is also described.

Animals↗
PubMed1989

Association of elevated expression of the c-erbB-2 protein with spread of breast cancer.

We analyzed amplification and expression of the c-erbB-2 gene in human breast cancers. Southern blot hybridization analysis demonstrated amplification of the c-erbB-2 gene in 10 out of 50 tumor DNAs examined. The degree of amplification was three- to twenty-fold relative to normal placenta. The c-erbB-2 protein could be analyzed in 39 tumor tissues of the 50 samples by immuno-blotting, and elevated expression of the c-erbB-2 protein was found in 15 cases. On the other hand, expression of the c-erbB-2 products was not detected in normal breast tissues either by immuno-blotting or by immuno-histological analysis. These data indicate that transcriptional and/or translational activation of c-erbB-2 might occur in some breast cancers in addition to activation by gene amplification. The elevated expression of the c-erbB-2 protein was most strongly correlated with lymph-node metastasis (P less than 0.001), suggesting that c-erbB-2 expression is involved in promotion of the lymph-node metastasis of human breast cancers. Therefore, immuno-histological diagnosis with anti-c-erbB-2 antibody might be useful as an indicator to predict lymph-node involvement in breast cancer.

Adenocarcinoma↗
PubMed1989

Life-span studies on spontaneous tumor development in the medaka (Oryzias latipes).

A total of 961 medaka, separated chronologically from the first to the fifth year of life, were examined for spontaneous tumor development. While no liver tumors were found in either male or female medaka under the age of 1 year and the incidence in 2-year-old fish was relatively low (males 1.9% and females 1.7%), they became more common with advancing age. The incidence was higher in females than in males from 3 to 5 years of age, reaching 7.1% in 5-year-old female stock. These liver tumors included a total of 12 adenomas and 9 hepatocellular carcinomas. The hepatocellular carcinomas were histologically well differentiated and were all observed in female medaka. Spontaneous tumors occurring in organs other than the liver were rare and sporadic. Four squamous cell carcinomas, 5 melanomas and 4 lymphosarcomas were observed with no sexual or pronounced age bias being evident. The squamous cell carcinomas developed in the surface epithelium with local invasion into the dermis. Melanomas occurred in the abdominal cavity and demonstrated systemic invasion into various parts of the body. Three out of the 4 lymphosarcomas arose from the inner part of the operculum suggesting that these tumors were of thymic origin. They also showed extensive invasion. The data indicate a particular susceptibility of older female medaka to liver but not other tumor development.

Adenoma↗
PubMed1989

Synthesis and central nervous system actions of thyrotropin-releasing hormone analogs containing a 1-substituted 2-oxoimidazolidine moiety.

A series of thyrotropin-releasing hormone (TRH) analogs in which the pyroglutamic acid residue was replaced by (S)-2-oxoimidazolidine-4-carboxylic acid (Oic-OH) and the related derivatives was prepared, and the central nervous system (CNS) actions were examined. Of these, 1-benzyl-Oic-His-Pro-NH2 (2c) showed the most potent activities, which were 1.5-8 times greater than those of TRH. Moreover, the thyrotropin (TSH)-releasing activity of 2c was about 1/16 times weaker than that of TRH.

Animals↗
PubMed1989

[The histological type and lymphatic permeation of diffuse infiltrative carcinoma of the stomach].

Although diffuse infiltrative carcinomas of the stomach are mostly composed of anaplastic/mucocellular type, some cases show tubular/trabeculoacinar carcinoma in a large or small part of the tumor. We have subdivided diffuse infiltrative carcinoma into two subtypes, mixed type and pure type, from the viewpoint of the carcinoma's histological structure and lymphatic permeation (LP). The former, or mixed type, includes a tubular/trabeculoacinar element in at least 10% of the tumor tissue, and shows a high tendency for LP. On the other hand, the latter, or pure type, consists almost exclusively of anaplastic/mucocellular carcinoma with a low tendency for LP. No difference in the frequency of LP between males and females was found in the pure type carcinomas, but a significantly higher frequency and grade of LP was observed in males in the mixed type carcinomas. Further, even in the pure type, the LP was rather frequent in people 60 or more years old. Thus, lymphatic permeation seems to be influenced not only by the histological type of the carcinoma but also by sex and age.

Adenocarcinoma↗