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Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 271 records · Page 15Linked to original sources
PubMed1996

Suppressing effects of 6-(2,5-dichlorophenyl)-2,4-diamino-1,3,5-triazine and related synthetic compounds on azoxymethane-induced aberrant crypt foci in rat colon.

The modifying effects of dietary administration of 6-(2,5-dichlorophenyl)-2,4-diamino-1,3,5-triazine and 5 related compounds on the occurrence of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce ACF. They also received the diet containing 200 ppm test compound for 5 weeks, starting one week before the first dosing of AOM. At the termination of experiment, all of the compounds had caused a significant reduction in ACF frequency, which might be associated with suppression of the expression of proliferation biomarkers. The apoptotic index in the colonic mucosal epithelium of rats killed at 6 h after the first AOM exposure revealed no blocking activity of the compounds.

Animals↗
PubMed1996

Aberrant DNA methylation on chromosome 16 is an early event in hepatocarcinogenesis.

In order to clarify the significance of DNA methylation in both earlier and later stages of hepatocarcinogenesis, the DNA methylation state on chromosome 16, on which loss of heterozygosity (LOH) has frequently been detected in human hepatocellular carcinomas (HCCs), was examined. DNA from primary HCCs and tissues showing chronic hepatitis and liver cirrhosis, which are considered to be precancerous conditions, was analyzed by digestion with methylation-sensitive and non-sensitive restriction enzymes. DNA hypermethylation at the D16S32, tyrosine aminotransferase (TAT) and D16S7 loci and hypomethylation at the D16S4 locus were detected in 18%, 58%, 20% and 48% of examined HCCs, respectively. Aberrant DNA methylation occurred more frequently in advanced HCCs than in early HCCs. Moreover, DNA hypermethylation at the D16S32, TAT and D16S7 loci was frequently observed in chronic hepatitis and liver cirrhosis. The incidence of DNA hypermethylation was higher than that of LOH (42% at the TAT locus). These data suggest that DNA hypermethylation might predispose the locus to allelic loss. Aberrant DNA methylation is a significant change which may participate in the early developmental stages of HCCs.

Carcinoma, Hepatocellular↗
PubMed1996

Raman spectra of human dentin mineral.

Human dentin mineral has been investigated by using micro-Raman spectroscopy. Fluorescence and thermal problems were largely avoided by preparing dentin samples by grinding and ultrasonic agitation in acetone. The Raman spectral features were consistent with those of impure hydroxyapatite containing CO3 and HPO4. While spectral differences between enamel and dentin were clearly observable as changes in the bandwidth of the PO4(3-)V1 band and the intensities of the OH-, CO3(2-) and HPO4(2-) bands, the technique could not detect spectral differences between coronal and root dentin. NaOCl, NaF and APF-gel treatments caused measurable changes in intensities of the bands due to CO3(2-) and HPO4(2-); the results were found to be useful for band assignments. After NaOCl treatment, the Raman bands, presumably due to amide and HPO4(2-), were lost, but the band intensity of the CO3(2-)V1 bands increased by 35-60%. This increase coincided with the appearance of a new broad band (250-300 cm-1). The same treatment on enamel caused no increase in the CO3(2-)V1 band intensity. This NaOCl-induced carbonate could be removed within 20 h in a 1000 ppm NaF solution. These findings indicate that the carbonate ions induced by the NaOCl treatment are presumably in or on the mineral surface. After 3 min of APF-gel treatment on NaOCl-pretreated dentin, the intensities of the hydroxyapatite phosphate bands dropped by approximately 20%, and newly formed CaF2 and HPO4 bands became observable.

Acidulated Phosphate Fluoride↗
PubMed1996

Evaluation of sodium fluorescein for quantitative diagnosis of root caries.

The diagnosis of root caries, in particular the judgment of the activity of a visually observed lesion, is difficult. Quantitative determination of lesion severity would allow the lesion to be monitored with time, so that an indication of lesion activity could be obtained. This paper describes a step in the development of a method that provides such a quantitative determination. Specifically, fluorescein sodium salt is used as a penetrating dye, the subject of study being the relationship between dye concentration and porosity in demineralized root dentin. Fourteen human third molars were demineralized in vitro (lactic acid CMC-gel, pH 5; in each of 6 groups for 4, 7, 11, 14, 18, and 21 days). Fluorescein sodium salt (0.2 g/L) was applied for 2 min. Thin slices (+/- 130 microns) were cut from the root surfaces without water cooling. The dye fluorescence radiance in the demineralized dentin was determined by means of a micro-Raman spectroscope and compared with the mineral loss profiles measured with transverse microradiography (TMR). The TMR data were corrected for the difference in measurement area between the two measurement systems. Corrected TMR profiles were compared with the corresponding fluorescence scans, showing linear correspondence. The correlation coefficient was r = 0.96. We conclude that, after uptake of fluorescein sodium salt for 2 min, the dye concentration in an artificially produced root-surface caries lesion is proportional to the amount of mineral lost from that lesion.

Dentin↗
PubMed1996

Inhibitory effect of antineoplaston A10 and AS2-1 on human hepatocellular carcinoma.

Antineoplastons, first described by Burzynski, are naturally occurring peptides and amino acid derivatives which control neoplastic growth. Antineoplaston A10 (3-pehnylacetylamino-2,6-piperidinedion) is the first chemically identified antineoplastons and when it is administered orally it is hydrolysed in pancreatic juice to phenylactylglutamine and phenylacetylisoglutamine in the ration of 4 to 1. These metabolites are water soluble and have antitumor effect, they are further degraded to pehnylacetic acid. The mixture of phenylacetylglutamine and phenylacetylisoglutamine in the ratio of 4 to 1 was formulated as Antineoplaston A10 injectable formulation. The mixture of phenylacetylglutamine and phenylacetic acid in the ratio of 1 to 4 was also shown to have antitumor effect in tissue culture study, then formulated as Antineoplaston AS2-1. The reported cytostatic inhibitory effect of A10 on human hepatocellular carcinoma cells and differentiation inducing effect of AS2-1 on various tumor cells suggest potential benefit for the treatment of human hepatocellular carcinoma since this tumor recurs frequently despite initial successful treatment. We report here the effects of Antineoplaston A10 and AS2-1 on cell proliferation, cell morphology, cell cycle, and DNA in human hepatocellular carcinoma cell lines. Both agents inhibited cell proliferation and increased the number of cells in G0 and G1 phases and Antineoplaston AS2-1 induced apoptosis, we also describe our clinical experience of a hepatocellula carcinoma (HCC) patient whose tumor, after incomplete trancathere arterial embolization (TAE) for a 7cm 7cm HCC, has been stable for more than 15 months during which time he has been taking Antineoplaston AS2-1 continuously without any serious adverse effects.

Antineoplastic Agents↗
PubMed1996

[Value of cancer-related oncoprotein expression as prognostic factors in breast-cancer with one to three axillary lymph nodes positive].

The patient group with breast carcinoma with one to three axillary lymph-node metastases (n1-3) shows a poorer prognosis than the node-negative one but a better prognosis than the group with 4 or more lymph node metastases. Univariate analysis shows that loss of bc1-2 expression, nuclear accumulation of p53, overexpression of c-erbB-2, age at diagnosis, menstrual status, tumor size, histologic grade, number of lymph nodes involved, and estrogen receptor were all significantly associated with the survival rates. Multivariate analysis demonstrated that menstrual status, number of involved lymph nodes, bc1-2, and p53 were significant predictors for overall survival, and that histological grade and number of nodes involved were significant predictors for disease-free survival. Combination of those factors would be useful to select highly aggressive n1-3 breast cancer group.

Axilla↗
PubMed1996

Inhibition of hepatocellular carcinoma development and erythrocyte polyamine levels in ODS rats fed on 3'-methyl-4-dimethylaminoazobenzene by hemicalcium ascorbate, 2-O-octadecylascorbic acid, and ascorbyl palmitate.

We examined the modifying effect of hemicalcium ascorbate (Ca-Asc), and its lipophilic derivatives, 2-O-octadecylascorbic acid (CV-3611) and ascorbyl palmitate (AscP), on hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) in ODS rats (a mutant unable to synthesize ascorbic acid). Male 14-week-old ODS rats were given a modified AIN-A diet or the diet containing 0.06% 3'-Me-DAB, and drinking water containing 0.1% ascorbic acid. Rats were divided into the following eight groups: Group 1, no treatment (basal diet alone); Group 2, Ca-Asc; Group 3, CV-3611; Group 4, AscP;Group 5, 3'-Me-DAB; Group 6, 3'-Me-DAB + Ca-Asc; Group 7, 3'-Me-DAB + CV-3611; and Group 8, 3'-Me-DAB + AscP. Ca-Asc (2 g/kg), CV-3611 (0.2 g/kg), and AscP (0.6 g/kg) was administered once every day by gavage. 3'-Me-DAB was given in the basal diet. After 17 weeks, animals were killed by exsanguination, and the liver was weighed and processed for histological examination. Treatment by CV-3611 exerted a marked inhibitory effect on the development of 3'-Me-DAB-induced hepatocellular carcinomas (HCC) as measured by multiplicity. Although less effective than CV-3611, Ca-Asc and AscP also showed inhibitory effect. We have also studied the correlation of erythrocyte (RBC) polyamine levels and HCC development. RBC polyamine levels were inhibited by Ca-Asc and its derivatives, indicating it may be a marker of hepatocarcinogenesis.

Animals↗
PubMed1996

[Molecular mechanisms of breast cancer progression].

Breast carcinoma is considered to occur as non-invasive carcinoma (DCIS) and to progress to the stage of invasive cancer. In DCIS, multiple gene and chromosome alterations are shown to occur already, and the pattern of alterations are concordant between DCIS and invasive components in most of individual tumors. Therefore, unknown molecular alterations are considered to exist that are involved in tumor invasion. A lot of alterations are also shown to occur in breast cancer cells, e.g., overexpression of growth factor receptors, cyclins and the molecules regulating cell-cycle, and cell-adhesion molecular. Clarification of signal-transducing mechanism of these molecules in cells and alterations of the system in cancer cells will be important as molecular mechanism of proliferation and progression of breast cancer. It is expected that the therapeutic strategy targetted to the control of these molecular events is developed in future.

Breast Neoplasms↗
PubMed1996

[Influenza-virus associated hemophagocytic syndrome in a patient with pernicious anemia].

A 59-year-old man with pernicious anemia (vitamin B12 deficiency) was admitted because of rapidly developing pancytopenia with the symptoms of influenza. Laboratory data indicated that the pancytopenia was manifested by influenza virus-associated hemophagocytic syndrome. In the patients with pernicious anemia, it is known that there are immunologic disturbances in either humoral and cellular immunity and increased hematopoiesis due to ineffective hematopoiesis. This patient was thought to have developed influenza virus-associated hemophagocytic syndrome due to the immunologic and hematopoietic abnormality in the pernicious anemia.

Anemia, Pernicious↗
PubMed1996

Demonstration of organotropic effects of chemopreventive agents in multiorgan carcinogenesis models.

Organotropic chemopreventive effects of three (pro)vitamins and three unsaturated fatty acids were examined using mouse and rat multiorgan carcinogenesis models. For the study of (pro)vitamins, male and female B6C3F1 mice were treated with N,N-diethylnitrosamine (DEN) and N-methyl-N-nitrosourea (MNU) during the first 11 weeks, then from weeks 12 to 32 they received alpha-carotene (0.4 mg/mouse), beta-carotene (0.4 mg/mouse) or alpha-tocopherol (40 mg/mouse) three times a week by gavage; control mice received vehicle alone. In male mice, alpha-carotene significantly reduced liver weights, representing a reduced tumour mass (P < 0.001), and alpha-carotene, beta-carotene and alpha-tocopherol significantly reduced the numbers of liver tumours (adenomas and carcinomas combined) (P < 0.001-0.01) as compared with control mice, the effects being greatest with alpha-carotene. In female mice, alpha-carotene significantly decreased the number of liver tumours (P < 0.001). In the lung, alpha-carotene and alpha-tocopherol reduced the area of lesions (hyperplasias and adenomas combined) only in males (P < 0.05). For the study of unsaturated fatty acids, F344 male rats were treated with DEN, MNU, N-butyl-N-hydroxybutylnitrosamine (BBN), 1,2-dimethylhydrazine (DMH) and N,N-bis(2-hydroxy)propylnitrosamine during the first 5 weeks, then from weeks 6 to 36 they were given docosahexaenoic acid (C22:6), eicosapentaenoic acid (C20:5) or linoleic acid (C18:2) at 1.0 g/rat, three times a week by gavage; control rats were treated with oleic acid (C18:1) using the same protocol. All animals were fed a low linoleic acid and calorie-adjusted basal diet during fatty acid administration. Docosahexaenoic acid and linoleic acid reduced tumours in the large and small intestines, respectively. However, they did not influence the yield of preneoplastic liver, lung, kidney, forestomach and urinary bladder lesions. The data thus provide evidence for organotropic effects of carotenoids and unsaturated fatty acids on carcinogenesis.

Animals↗
PubMed1996

A micro-Raman spectroscopic study of hydrazine-treated human dental calculus.

Hydrazine has been used to remove organic components and to isolate the mineral(s) from human calculus. Micro-Raman measurements were performed on the mineral phase. After the hydrazine-treatment, not only a large reduction in fluorescence but also an increase in Raman signal was observed. The treatment was essential in minimizing thermally-induced chemical changes which could otherwise occur to the original calculus mineral due to the intense laser light. The Raman spectral features of the mineral were nearly all identical among the Raman spectra obtained at many randomly-selected sites by the micro-Raman microbe with a lateral resolution of approximately 1 micron, and were consistent with those of impure hydroxyapatite containing CO3(2-) and HPO4(2-). The spectra contained typical hydroxyapatite bands including PO4(3-)bands of the v1, v2, v3 and v4 modes and one OH- stretch band. Other minor bands due to the CO3(2-) v1 and v3 modes and bands possibly due to the HPO4(2-) v1, v2 and v4 modes were observable by the technique despite the hydrazine-treatment that could in principle remove the HPO4 and CO3 ions from the mineral. In comparison with pure synthetic hydroxyapatite, the intensity of the OH- stretch band relative to that of the PO4(3-) v1 band was approximately 70% weaker, and the bandwidth of the phosphate v1 band was 200% broader, reflecting various crystal imperfections presumably present in the calculus mineral.

Adult↗
PubMed1995

An abnormal fibrinogen Fukuoka II (Gly-B beta 15-->Cys) characterized by defective fibrin lateral association and mixed disulfide formation.

A dysfibrinogenemia was attributable to a single amino acid substitution from glycine to cysteine at residue 15 of the B beta chain in a fibrinogen molecule designated as fibrinogen Fukuoka II. The fibrinogen Fukuoka II showed prolonged thrombin and reptilase times and impaired fibrinopeptide B release by thrombin, resulting in abolition of fibrin monomer repolymerization under physiological conditions. Repolymerization of the des-(B beta 1-42)-fibrin monomers, however, was not distinguished from the normal pattern of des-(B beta 1-42)-fibrin monomers, suggesting that no other abnormality existed in fibrinogen Fukuoka II. Although an additional cysteine was substituted at residue 15 of the B beta chain, fibrinogen Fukuoka II had no free sulfhydryl group within the molecule. Instead, fibrinogen Fukuoka II formed a disulfide bond with cysteine, albumin, another mutated B beta chain within the same molecule, or intermolecular dimeric fibrinogen Fukuoka II. The mutation in fibrinogen Fukuoka II was the same as that in fibrinogen Ise published previously (Yoshida, N., Wada, H., Morita, K., Hirata, H., Matsuda, M., Yamazumi, K., Asakura, S., and Shirakawa, S. (1991) Blood 77, 1958-1963). Fibrinogen Ise, however, has been described as having prolonged thrombin time but normal reptilase time. Reasons for the discrepancy were not clear. Analysis of the B beta 1-42 fragment showed that fibrinogen was heterogeneous at position 31 of the B beta chain with respect to proline or hydroxyproline.

Amino Acid Sequence↗
PubMed1995

Higher Level of P-glycoprotein Expression in Human Breast Cancer Cells after Radiation Therapy.

We investigated the effects of radiation on the expression of p53 protein and P-gp in breast cancer cells. Thirty-two preoperatively irradiated surgical specimens of stage I primary breast cancer were examined, and 39 surgical specimens of non-irradiated stage I breast cancer were selected as a control group. p53 and P-gp expression was detected by an immunohistochemical technique using rabbit polyclonal antibodies (RSP-53 and NCL-pGLYPp). The expression of p53 protein, defined as a nuclear immunoreaction in 20% or more of tumor cells, was detected in 4(13%) of the 32 cases in the irradiated group and 7 (18%) of the 39 cases in the non-irradiated group without any statistically significant difference. The expression of P-gp, defined as the presence of strong staining in more than 75% of the tumor cells, was detected in 19 (59%) of the cases in the irradiated group and 12(31%) of the cases in the non-irradiated group. P-gp expression was significantly higher in the former group than in the latter (P <0.05). There was no significant difference in P-gp expression between the stromal invasive component and the intraductal component in either the irradiated or the non-irradiated group. Radiotherapy possibly induces membranous P-gp expression in human breast cancer cells.

Journal Article↗
PubMed1995

Stimulation of sky receptor tyrosine kinase by the product of growth arrest-specific gene 6.

Sky (also called Rse, Brt, and Tyro3) is a member of a subfamily of related receptor tyrosine kinases, including Axl/Ufo/Ark and c-Eyk/Mer. We obtained evidence that Gas6 (the product of growth arrest-specific gene 6) is a ligand of the Sky receptor tyrosine kinase. Gas6, but not protein S (an anticoagulant protein structurally similar to Gas6), specifically bound to the soluble form of Sky (Sky-Fc), composed of the extracellular domain of Sky fused to the Fc domain of human immunoglobulin G1. The native and recombinant Gas6, but not protein S, stimulated tyrosine phosphorylation of Sky ectopically expressed in Chinese hamster ovary cells. Stimulation of Sky in response to Gas6 was inhibited by Sky-Fc. The half-maximal concentration of Gas6 that stimulated Sky was about 1 nM. Thus, Gas6 as a ligand for Sky specifically binds to and stimulates Sky receptor tyrosine kinase.

Animals↗
PubMed1995

Structure determination of the octa- and decasaccharide sequences isolated from the carbohydrate-protein linkage region of porcine intestinal heparin.

Previously we isolated a tetrasaccharide-serine and a hexasaccharide-serine from the carbohydrate-protein linkage region of porcine intestinal heparin after digestion with a mixture of Flavobacterium heparinase and heparitinases I and II (Sugahara, K., Yamada, S., Yoshida, K., de Waard, P., and Vliegenthart, J.F.G. (1992) J. Biol. Chem. 267, 1528-1533). In this study four longer carbohydrate sequences (I-IV) attached to Ser or a dipeptide (Ser-Gly or Gly-Ser), which accounted for at least 18.2% of the total linkage region, were isolated from the same heparin preparation after digestion with heparinase only. IV was successfully isolated only after subsequent digestion with glycuronate-2-sulfatase. Their structures were determined by chemical and enzymatic analyses and 1H NMR spectroscopy and found to be the following octa- and decasaccharide sequences attached to Ser in a molar ratio of 1.1:2.3:1.0:1.3: delta HexA(2S)alpha 1-4GlcN(NS,6S)alpha 1-4GlcA beta 1-4GlcNAc alpha 1-4- GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser (I), delta HexA(2S)alpha 1- 4GlcN(NS,6S)alpha 1-4IdoA alpha 1-4GlcNAc alpha 1-4GlcA beta 1- 3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser (II), delta HexA(2S)alpha 1- 4GlcN(NS,6S)alpha 1- 4IdoA alpha 1-4GlcNAc alpha 1-4GlcA beta 1-4GlcNAc-alpha 1- 4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser (III), delta HexA alpha 1-4GlcN(NS,6S)alpha 1-4IdoA alpha 1-4GlcNAc(6S)alpha 1- 4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser (IV) (delta HexA, GlcA, IdoA, and GlcN represent 4,5-unsaturated hexuronic acid, D-glucuronic acid, L-iduronic acid, and D-glucosamine, whereas 2S, 6S, and NS stand for 2-sulfate, 6-sulfate, and N-sulfate, respectively). I and II contained 1 mol of Gly in addition to Ser. The four structures indicate that sulfation in heparin chains takes place on the monosaccharide residues located in closer vicinity to the core protein than found for heparan sulfate chains and that there exist at least several heparin subclass chains with different linkage region structures. The significance of the isolated structures is discussed in relation to the biological functions and the biosynthetic mechanisms of heparin.

Amino Acids↗