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H Tsuda

Publications and source records attributed to H Tsuda.

At least 253 records · Page 14Linked to original sources
PubMed1997

[Etiological analysis of thrombophilia].

We have established a system for etiological analysis of thrombophilia which includes assays of antithrombin III, protein C, protein S, plasminogen, fibrinogen, heparin cofactor II and lupus anticoagulants as well as gene analysis. The analysis conducted on 115 patients with venous thrombosis, arterial thrombosis and small vessel thrombosis revealed that forty-one patients(36% of the examined patients) were accompanied with decreased activities of protein S, protein C, antithrombin III and plasminogen. Eleven candidate causal mutations were found by gene analysis. These studies indicate that a comprehensive examination is instrumental in identifying and confirming the etiology in patients with thrombophilia.

Antithrombin III↗
PubMed1996

Polydispersity in sulfation profile of oligosaccharide alditols isolated from the protein-linkage region and the repeating disaccharide region of chondroitin 4-sulfate of bovine nasal septal cartilage.

Proteoglycans of bovine nasal septal cartilage bear predominantly chondroitin 4-sulfate. After exhaustive chondroitinase ABC digestion of a chondromucoprotein preparation rich in proteoglycans and subsequent reductive beta-elimination, five hexasaccharide alditols were isolated from the glycosaminoglycan-protein linkage region. They were analyzed by enzymatic digestion in conjunction with HPLC and by one-dimensional and two-dimensional 1H-NMR spectroscopy. They share the conventional core saccharide structure delta 4.5HexA alpha 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl-ol (where delta 4.5HexA is 4,5-unsaturated hexuronic acid), but have different sulfation profiles. One compound (I) does not contain sulfate. Two of the three monosulfated compounds (II and III) have an O-sulfate group at either C6 or at C4 of the GalNAc residue. The other monosulfated compound (IV) is hitherto unreported and has a O-sulfate at C4 of the Gal residue preceding the GlcA residue, whereas the GalNAc is not sulfated. The disulfated compound (V) has sulfate groups at C4 of both the Gal residue preceding GlcA and the GalNAc residue. The molar ratio of compounds I-V is 38.3:5.9:43.0:1.6:11.2. The structural heterogeneity of these hexasaccharide alditols reflects the polydispersity in the linkage region of the chondroitin sulfate chains. In addition, two trisaccharide and two tetrasaccharide alditols derived from the repeating disaccharide region of the chondroitin sulfate chains were also isolated. Their structures were unambiguously determined by enzymatic analysis and by 1H-NMR spectroscopy as delta 4.5HexA alpha 1-3GalNAc(4-O- or 6-O-sulfate)beta 1-4GlcA-ol and delta 4.5HexA alpha 1-3GalNAc(4-O- or 6-O-sulfate) beta 1-4GlcA beta 1-3GalNAc(4-O-sulfate)-ol, respectively.

Animals↗
PubMed1996

Promotion potential of tamoxifen on hepatocarcinogenesis in female SD or F344 rats initiated with diethylnitrosamine.

The liver promotion potential of tamoxifen (TAM), which has been widely used in the treatment of hormone-dependent breast cancers, was investigated using female SD or F344 rat initiated with diethylnitrosamine (DEN). In Experiment 1, 45 newborn female SD rats were administered DEN (100 mg/kg, i.p.) (Groups 1 and 2) or saline (Group 3) 24 h after birth. After weaning at week 3, Groups 1 and 3 were subcutaneously injected with TAM citrate (1 mg/rat per day), suspended in corn oil, in the subscapular region, while Group 2 was given the vehicle alone (s.c.) daily for 9 weeks, and killed at week 12. In Experiment 2, 70 female F344 rats at 7 weeks of age were divided into five groups. All animals were initially given DEN (200 mg/kg i.p.) for initiation. Two weeks later Groups 1-4 were given diets containing 100, 250, 500 ppm TAM, or 500 ppm PB for 6 weeks, respectively, while Group 5 was administered basal diet as a control for the same period. The rats were subjected to two-thirds partial hepatectomy (PH) at week 3 and were killed at week 8. The enhanced development of glutathione S-transferase-placental form (GST-P)-positive liver cell foci after DEN exposure in both newborn SD and adult F344 rat medium-term liver bioassay models (Experiments 1 and 2). This suggests that TAM exerts promotion potential for hepatocarcinogenesis in female rats.

Animals↗
PubMed1996

An intensive chemotherapy of adult T-cell leukemia/lymphoma: CHOP followed by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support.

SUMMARY: An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in adult T-cell leukemia/lymphoma (ATLL) patients in a multiinstitutional, cooperative study. Vincristine 1 mg/m2 i.v. day 1, Adriamycin 40 mg/m2 i.v. day 1, cyclophosphamide 400 mg/m2 i.v. day 1, prednisolone 40 mg/m2 i.v. days 1 to 3 and 8 to 10, etoposide 35 mg/m2 i.v. days 1 to 8, vindesine 2 mg/m2 i.v. day 8, ranimustine 50 mg/m2 i.v. day 8, mitoxantrone 7 mg/m2 i.v. day 8, and G-CSF 50 mg/m2 s.c. days 9 to 21 were given for 2 to 4 courses every 3 weeks to 83 patients with ATLL. Complete remission (CR) and partial remission (PR) were achieved in 35.8 and 38.3 percent, respectively, of 81 evaluable patients. The median survival of all patients was 8.5 months, with a predicted 3-year survival of 13.5 percent by the Kaplan-Meier method. The median duration of response was 7.6 months (range 0.2-42.7), and 13 patients were alive. Their median survival time was 29.1 months (range 19.2-44.7). In 67.6 percent of courses, white blood cell (WBC) nadirs were < 1.0 x 10(9)/L. Days required for the recovery of WBC from the nadir to > 1.0 x 10(9)/L were <5 days in 71.4 percent of the treatment courses. The G-CSF supported an intensified chemotherapy regimen for ATLL and yielded better response rate and longer survival compared to previous reports in Japan. Because duration of remission is still short, further studies of postremission therapy or other strategies are warranted.

Adult↗
PubMed1996

Structures of five sulfated hexasaccharides prepared from porcine intestinal heparin using bacterial heparinase. Structural variants with apparent biosynthetic precursor-product relationships for the antithrombin III-binding site.

Porcine intestinal heparin was extensively digested with Flavobacterium heparinase and size-fractionated by gel chromatography. Subfractionation of the hexasaccharide fraction by anion exchange high pressure liquid chromatography yielded 10 fractions. Six contained oligosaccharides derived from the repeating disaccharide region, whereas four contained glycoserines from the glycosaminoglycan-protein linkage region. The latter structures were reported recently (Sugahara, K., Tsuda, H., Yoshida, K., Yamada, S., de Beer, T., and Vliegenthart, J.F.G. (1995) J. Biol. Chem. 270, 22914-22923). In this study, the structures of one tetra- and five hexasaccharides from the repeat region were determined by chemical and enzymatic analyses as well as 500-MHz 1H NMR spectroscopy. The tetrasaccharide has the hexasulfated structure typical of heparin. The five hexa- or heptasulfated hexasaccharides share the common core pentasulfated structure delta HexA(2S) alpha 1-4GlcN-(NS, 6S) alpha 1-4IdoA alpha/GlcA beta 1-4GlcN(6S) alpha 1-4GlcA beta 1-4GlcN (NS) with one or two additional sulfate groups (delta HexA, GlcN, IdoA, and GlcA represent 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid, D-glucosamine, L-iduronic acid, and D-glucuronic acid, whereas 2S, 6S and NS stand for 2-O-, 6-O-, and 2-N-sulfate, respectively). Three components have the following hitherto unreported structures: delta HexA(2S) alpha 1-4GlcN(NS, 6S) alpha 1-4GlcA beta 1-4GlcN(NS, 6S) alpha 1-4GlcA beta 1-4GlcN(NS,6S), delta HexA(2S) alpha 1-4GlcN(NS, 6S) alpha 1-4IdoA alpha 1-4GlcNAc(6S)-alpha 1-4GlcA beta 1-4GlcN(NS, 3S), and delta HexA(2S) alpha 1-4GlcN-(NS,6S) alpha 1-4IdoA (2S) alpha 1-4GlcNAc(6S) alpha 1-4GlcA beta 1-4GlcN(NS, 6S). Two of the five hexasaccharides are structural variants derived from the antithrombin III-binding sites containing 3-O-sulfated GlcN at the reducing termini with or without a 6-O-sulfate group on the reducing N,3-disulfated GlcN residue. Another contains the structure identical to that of the above heptasulfated antithrombin III-binding site fragment but lacks the 3-O-sulfate group and therefore is a pro-form for the binding site. Another has an extra sulfate group on the internal IdoA residue of this pro-form and therefore can be considered to have diverged from the binding site in the biosynthetic pathway. Thus, the isolated hexasacharides in this study include the three overlapping pairs of structural variants with an apparent biosynthetic precursor-product relationship, which may reflect biosynthetic regulatory mechanisms of the binding site.

Animals↗
PubMed1996

A malignant granular cell tumor of the stomach: report of a case.

We report herein what to our knowledge is the first documented case of a malignant granular cell tumor of the stomach. A 64-year-old woman was admitted to our hospital for investigation of gastric submucosal tumor. Endoscopy disclosed a large hemispherical mass located on the lesser curvature at the gastric antrum with a normal mucosal surface, and computed tomography (CT) revealed a solid tumor about 7 cm in diameter with clear margins. A laparotomy was carried out under the preoperative diagnosis of leiomyosarcoma of the stomach. A tumor was found in the gastric antrum, with extragastric extension to the hepatic hilum, and a distal partial gastrectomy was performed. However, a follow-up CT scan performed 21 months postoperatively revealed a solid tumor of about 10 cm in diameter with clear margins, situated between the liver and the transverse colon. This was subsequently diagnosed as local recurrence and a resection was carried out. Microscopic examination of both the first and second specimens showed that the tumor cells were large and polygonal, with medullary proliferation and finely granular eosinophilic cytoplasm. Mitotic figures were also present. Thus, the lesion was diagnosed as a malignant granular cell tumor of the stomach from the clinical and pathological findings.

Cell Division↗
PubMed1996

Successful treatment of virus-associated haemophagocytic syndrome in adults by cyclosporin A supported by granulocyte colony-stimulating factor.

Two young adult patients with typical virus-associated haemophagocytic syndrome (VAHS) were treated with cyclosporin A and granulocyte colony-stimulating factor (G-CSF). Clinical symptoms such as high fever and malaise disappeared rapidly with concurrent haematological improvement in both patients. The serum levels of interleukin-6 (IL-6), soluble IL-2 receptor, tumour necrosis factor and macrophage-CSF were all elevated before treatment but that of G-CSF was not. The dramatic effect of cyclosporin A observed implies that it efficiently and rapidly suppresses the cytokine storm caused by dysregulated T cells in VAHS. In addition, G-CSF may promote haematological recovery without syndrome regression. We believe that the combination of cyclosporin A and G-CSF may be effective, at least in selected patients with VAHS. Further studies are required to confirm its role as first-line therapy for adult patients with VAHS.

Adult↗
PubMed1996

Decreased connexin32 and a characteristic enzyme phenotype in clofibrate-induced preneoplastic lesions not shared with spontaneously occurring lesions in the rat liver.

Two different types of focal preneoplastic lesions, tentatively named Type I and II lesions, were recognized in the liver of rats chronically treated with clofibrate for 104 weeks. Type I lesions were characterized by mostly negative glucose-6-phosphate dehydrogenase (G6PD) activity (6 out of 10, 60%) and positive expression of succinate dehydrogenase (10 out of 10, 100%), in addition to the previously documented complete lack of expression of glutathione S-transferase, placental form (GST-P) and gamma-glutamyl transpeptidase (GGT). Furthermore, most importantly, Type I lesions exhibited a clear decrease in immunohistochemically demonstrated connexin32 (Cx32) spot counts on their hepatocyte membranes, similarly to nitrosamine-induced lesions. In contrast, Type II lesions, mostly small in size and positively expressing GST-P and/or GGT and G6PD, similarly to their previously reported nitrosamine-induced counterparts, did not exhibit a significant decrease in Cx32 count. In addition, spontaneously occurring lesions, again sharing the same enzyme phenotype, did not show a decrease in Cx32. The results indicate that: (i) a clear distinction between the two lesions, with Type I being involved in clofibrate-induced tumors and Type II being more likely to be spontaneous in nature; (ii) a decrease in Cx32 is closely linked to lesion development and possibly stage of progression, irrespective of the enzyme phenotype and the applied carcinogen; (iii) the unaltered condition of Cx32 may suggest a slow growing or non-progressive nature.

Animals↗
PubMed1996

Cx32 gene mutation in a chemically induced rat liver tumour.

Cx32 is a major gap junction protein of the liver and is often aberrantly expressed in liver tumours. We have studied mutation of the Cx32 gene during chemically induced hepatocarcinogenesis. DNA from 12 rat liver tumours induced by diethylnitrosamine or N-ethyl-N-hydroxyethylnitrosamine (EHEN) was analysed by the PCR/SSCP method. One tumour induced by EHEN harboured a G--> A transition mutation at codon 220, substituting His for Arg. When the mutant DNA was transfected into HeLa cells, which are deficient in gap junctional intercellular communication (GJIC), GJIC recovered, as in HeLa cells transfected with the wild-type Cx32 gene. Moreover, GJIC was modulated by cAMP, 12-O-tetradecanoylphorbol-13-acetate and lysophosphatidic acid similarly in mutant and wild-type Cx32 transfectants. These results suggest that Cx32 gene mutations are rarely involved in rat hepatocarcinogenesis and that the mutation found in a tumour may be functionally silent.

Adenoma↗
PubMed1996

Prognostic value of histopathological therapeutic effects and mitotic index in locally advanced breast cancers after neoadjuvant chemotherapy.

A study was conducted to examine whether or not the histopathological therapeutic effects of preoperative chemotherapy could be useful for determining prognosis in women with locally advanced breast cancer. The patients were 37 women with locally advanced breast cancer who received preoperative chemotherapy between 1977 and 1987. The histological grade of malignancy (HGM) and histopathological therapeutic effects of chemotherapy (TEf) were examined in resected specimens. Patients with HGM 3 showed a poorer 10-year overall survival (38%) than those with HGM 1 or 2 (62%). Patients showing a better histopathological response (TEf 1b plus 2) had a poorer 10-year overall survival (20%) than those with a poorer response (TEf 0 plus 1a) (60%). Therapeutic effects were significantly related to histological grade, nuclear atypia and mitotic index (p = 0.03, 0.005 and 0.002, respectively). Histopathological therapeutic effects were not directly correlated with patient prognosis. Cox proportional hazard regression analysis revealed that mitotic index was the most significant prognostic factor related to 10-year overall survival.

Adult↗
PubMed1996

Effect of conventional mechanical ventilation and jet ventilation on airway pressure in dogs and plastic models with tracheal stenosis.

OBJECTIVE: To evaluate the effect of jet ventilation on tracheal stenosis in dogs and plastic models. DESIGN: Prospective, randomized trial in dogs, and multitrial tests in tracheal stenosis models. SETTING: Animal laboratory in a university setting. INTERVENTIONS: Tracheal stenosis was surgically created around the middle of the trachea. Conventional mechanical ventilation and jet ventilation were compared at the same value of Paco2 in dogs and at the same tidal volume in tracheal stenosis models. SUBJECTS: Twelve mongrel dogs and four types of plastic models with combinations of short or long stenosis and fluid or nonfluid stenosis. MEASUREMENTS AND MAIN RESULTS: Canine Studies. Mean peak peak airway pressure values at the distal and proximal portion of the stenosis, and the end-expiratory pressure at the distal portion of the stenosis, were significantly higher during conventional mechanical ventilation than during jet ventilation. The mean values of arterial pressure, pulmonary arterial pressure, central venous pressure, and cardiac output did not change significantly between conventional mechanical ventilation and jet ventilation, except for the pulmonary artery occlusion pressure valve. Plastic Mold Studies. peak airway pressure and end-expiratory airway pressure at the poststenotic trachea during jet ventilation with the model lung were significantly lower than during conventional mechanical ventilation. The difference in peak airway pressure, and end-expiratory airway pressure values between jet ventilation and conventional mechanical ventilation increased more in short stenosis and nonfluid stenosis. CONCLUSIONS: The jet flow that struck the portion of the stenosed wall reversed direction, even during early expiration. Therefore, the expiration during jet ventilation was facilitated more by the reversed flow than by the expiration during conventional mechanical ventilation. This reversed flow may provide lower end-expiratory airway pressure at the poststenotic portion with jet ventilation than with conventional mechanical ventilation. We conclude that jet ventilation was a useful method of ventilation in cases with tracheal stenosis, especially nonfluid and short stenosis.

Animals↗
PubMed1996

Hepatocellular carcinoma induction in LEC rats by a low dose of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.

A food-borne heterocyclic amine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), induces hepatocellular carcinomas (HCCs) in F344 male rats at an incidence of 95%, when fed in the diet at 400 ppm for 61 weeks. In this study, the effect of a low dose of MeIQx was examined in Long-Evans with cinnamon-like coat color (LEC) rats, which have a mutation in Atp7b and suffer from hereditary hepatitis and HCCs, with high levels of copper accumulation in the liver. Rats of the LEC and Long-Evans with agouti coat color (LEA) sibling lines were given a diet containing 40 ppm MeIQx from the age of 23 weeks to 63 weeks, for a total administration period of 40 weeks. In LEC rats, HCCs were observed in 8/8 animals administered MeIQx, and 2/8 rats receiving a normal diet. The number of HCCs per rat (mean +/- SD) was 2.8 +/- 2.0 and 0.3 +/- 0.5, respectively. In the LEA rats, however, no tumors were induced by administration of MeIQx. These results indicate that damaged liver associated with compensatory cell proliferation is much more susceptible to chemical hepatocarcinogens, including MeIQx, than the normal liver.

Alanine Transaminase↗
PubMed1996

Modifying influence of swine-serum-induced liver fibrosis on development of preneoplastic lesions in rat liver.

Modifying effects of fibrosis or a cirrhotic state, caused by treatment with swine serum (SS), on the induction of preneoplastic focal lesions were assessed in a rat medium-term liver bioassay model for the detection of environmental carcinogens, in which the test compound is administered during the promotion phase after initiation with diethylnitrosamine. In experiment I, repeated intraperitoneal administration of SS concomitantly with the hepatopromoting agent deoxycholic acid (DCA) or phenobarbital (PB) resulted in a cirrhotic state and a significant increase in the number or size of preneoplastic glutathione S-transferase placental form (GST-P)-positive liver cell foci as compared to the corresponding DCA or PB alone groups. In experiment II, SS was given prior to commencement of the same medium-term bioassay system, in which a known hepatopromoting agent, DCA, 17-alpha-ethynylestradiol, or 2-acetylaminofluorene, was applied. In this case, the liver did not show obvious cirrhotic change and, rather than any enhancement, slight inhibition of promotion occurred. The results indicate that a coexisting, but not a pre-existing, cirrhotic condition acts to increase growth pressure on GST-P+ preneoplastic foci, and suggest that concomitant administration of SS with the promoting agent could be applied to improve the sensitivity of the assay protocol.

2-Acetylaminofluorene↗
PubMed1996

Decreased levels of 2-amino-3-methylimidazo[4,5-f]quinoline-DNA adducts in rats treated with beta-carotene, alpha-tocopherol and freeze-dried aloe.

To assess mechanisms of chemoprevention of hepatocarcinogenesis by trans-beta-carotene (beta-C), DL-alpha-tocopherol (alpha-T), and freeze-dried whole leaves of Kidachi aloe (Aloe), formation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA adducts was measured by 32P-post-labeling analysis, and CYP1A1 and CYP1A2 protein levels were analyzed by ELISA. Group 1 rats were fed diet containing 0.02% beta-C, 1.5% alpha-T or 30% Aloe over an 8-day period, while group 2 was given basal diet alone. On day 7, all animals were subjected to two-thirds partial hepatectomy (PH). Twelve hours after PH, they received a single dose of the carcinogenic food pyrolysate IQ (100 mg/kg) intragastrically, to initiate hepatocarcinogenesis. Rats were killed 6, 12, 24 and 48 h after IQ administration. The levels of adducts, expressed as relative adduct labeling values in rats treated with beta-C, alpha-T and Aloe, were decreased as compared with the control group at hour 24 (36 h after PH), with a significant difference in the case of the beta-C group (46.4% of the control value). Similarly, all showed a tendency for decrease at hour 48. Furthermore, the levels of CYP1A2, known to be responsible for activation of IQ, showed a significant reduction at hour 24. It is concluded that beta-C, and possibly also alpha-T and Aloe, have the potential to reduce IQ-DNA adduct formation, presumably as a result of decreased formation of active metabolites. The results may explain, at least in part, the previously observed inhibitory effects of these compounds on induction of preneoplastic hepatocellular lesions.

Aloe↗
PubMed1996

Fibrotic focus in invasive ductal carcinoma: an indicator of high tumor aggressiveness.

Histological examination of invasive ductal carcinoma of the breast often demonstrates the presence of an extensive central fibrotic focus (FF). The clinicopathological significance of the FF, or scar, in primary invasive ductal carcinoma is still ambiguous. One hundred and fifty-three cases of invasive ductal carcinoma (IDC) were classified into two groups, those with and those without FF. The differences in frequency of immunohistochemically detected overexpression of c-erbB-2 protein and nuclear accumulation of p53 protein, and the labeling index of proliferating cell nuclear antigen (PCNA), as well as histopathological parameters were compared between these two groups. IDCs smaller than 50 mm with FF showed a higher frequency of high-grade tumors, a higher frequency of lymph node metastasis, and a significantly higher frequency of c-erbB-2 protein overexpression than those without FF. In tumors of 20 mm or less, the incidence of nuclear accumulation of p53 protein was significantly higher in tumors with than those without FF. Tumors with FF showed a significantly higher PCNA labeling index than those without FF, regardless of tumor size. The present results indicate that the presence of FF is an important clinicopathological parameter associated with a higher degree of malignancy in IDCs, especially those smaller than 50 mm. Therefore, dividing IDCs into those with and those without FF appears to be meaningful clinicopathologically.

Adult↗