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Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 505 records · Page 28Linked to original sources
PubMed1988

Positive influence of dietary deoxycholic acid on development of pre-neoplastic lesions initiated by N-methyl-N-nitrosourea in rat liver.

The effect of deoxycholic acid (DCA) treatment subsequent to initiation of F344 male rats with N-methyl-N-nitrosourea (MNU), a wide spectrum carcinogen inducing tumors in many organs, was investigated. Rats were initially given four doses of MNU (50 mg/kg) i.p. within a 2-week period combined with a two-thirds partial hepatectomy performed at day 7 and then placed on basal diet containing DCA at concentrations of 0.313, 0.125, 0.050 and 0.020% for 21 weeks prior to final sacrifice. All organs studied were carefully examined histologically and histochemically for development of neoplastic and pre-neoplastic lesions. DCA enhanced the induction of glutathione S-transferase positive (GST-P+) liver cell foci in a dose-related manner. Furthermore groups of rats given DCA without prior MNU administration also developed dose-dependent numbers of pre-neoplastic liver lesions. In addition, increased numbers of small intestine tumors were apparent in DCA-treated animals although the difference was not significant. Induction of tumors in the thyroids, Zymbal glands, skin and peripheral nerves was not affected. The results indicate that DCA is a strong promoter of hepatocarcinogenesis with possible complete carcinogenicity in the liver and promotion potential for tumor development in the small intestine.

Animals↗
PubMed1988

Hemodynamic relationship between renal venous pressure and blood flow regulation during positive end-expiratory pressure.

The hemodynamic relationship between renal venous pressure (RVP) and renal blood flow (RBF) during PEEP was investigated using adult mongrel dogs. When continuous mechanical ventilation (CMV) with 10 cm H2O of PEEP was applied to dogs previously on CMV with zero PEEP, RVP increased from 6.6 to 8.7 mm Hg (p less than .01), and left RBF decreased from 66 to 57 ml/min (p less than .05). RBF recovered by 49% of the difference as soon as PEEP was discontinued when the RVP elevation was maintained at the level observed during 10 cm H2O of PEEP. With 20 cm H2O of PEEP, RVP increased further to 10 mm Hg (p less than .01) and left RBF decreased to 48 ml/min (p less than .05). When the left renal vein was occluded and the RVP was maintained at the level seen during 20 cm H2O of PEEP, left RBF recovered only 50% of the difference from the flow during zero PEEP. We conclude that the reduction in RBF with PEEP application is caused by several factors; however, RVP elevation during CMV with PEEP is influential in decreasing RBF.

Animals↗
PubMed1988

A new medium-term bioassay system for detection of environmental carcinogens using diethylnitrosamine-initiated rat liver followed by D-galactosamine treatment and partial hepatectomy.

The effects of D-galactosamine on induction of preneoplastic glutathione S-transferase placental form positive liver foci were investigated in F344 rats pretreated with diethylnitrosamine (DEN) in an attempt to improve the predictive value of the medium-term bioassay system developed in our laboratory. Two weeks after the initial single ip dose (200 mg/kg) of DEN, administration of test compounds was commenced simultaneously with an ip injection of D-galactosamine at a dose of 300 mg/kg body wt. All rats were then subjected to two-thirds partial hepatectomy (PH) at week 5 and sacrificed for assessment of lesion yield at week 8. Measurement and comparison of the numbers and areas of glutathione S-transferase placental form positive (GST-P+) foci per cm2 revealed a positive response to more carcinogens, including non-hepatocarcinogens, than did the same bioassay system without injection of D-galactosamine. Thus the results suggest that inclusion of this extra proliferative stimulus may improve the medium-term detection of carcinogens and modifiers.

Animals↗
PubMed1988

H-ras p21 and peanut lectin immunoreactivity of hyperplastic, preneoplastic and neoplastic urinary bladder lesions in rats.

Hyperplastic, preneoplastic and neoplastic urinary bladder lesions induced by bladder carcinogens and toxins in the rat were evaluated for immunoreactivity with polyclonal or monoclonal antibodies to H-ras p21 or binding to peanut lectin with avidin-biotin immunocytochemistry. A low proportion (less than 20%) of hyperplastic and neoplastic bladder lesions induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine and fixed in Bouin's fixative only were immunoreactive on the cell membrane with the antibodies to H-ras p21. Lectin binding was found for these lesions, as well, even in formalin-fixed tissue and for lesions induced by other carcinogens, but not in regenerative bladder hyperplasias after cyclophosphamide exposure or in bladder exposed to bladder tumor promoters. The latter lesions were also not immunoreactive with antibodies to p21. Our results suggest that this relatively simple technique might be used for identification and screening of tumors for involvement of ras oncogenes and carcinogen initiation.

Animals↗
PubMed1988

Wide-spectrum initiation models: possible applications to medium-term multiple organ bioassays for carcinogenesis modifiers.

Two wide-spectrum initiation models were investigated in F344 male rats. Model I: After sequential treatment with diethylnitrosamine (DEN), N-methylnitrosourea (MNU) and dihydroxy-di-N-propylnitrosamine (DHPN), animals were given phenobarbital (PB) or N,N-dibutylnitrosamine (DBN) as a test compound for 14 weeks and sacrificed at week 18. Model II: Animals were treated with DHPN, followed by N-ethyl-N-hydroxyethylnitrosamine (EHEN), and then 3,2'-dimethyl-4-aminobiphenyl (DMAB) as initiators and were subsequently given 3-methylcholanthrene (MCA) or PB as a test compound for 11 weeks. Animals were sacrificed 16 weeks after the commencement. In both models, assessment of lesion yield revealed significant enhancement of carcinogenesis by the test compounds in their respective target organs. Since, in many cases, treatment with PB, DBN and MCA subsequent to the combined initiation procedures brought about a marked increase in lesion development, far greater than a simple sum of the yields given by initiators and test compounds alone, the presently described approach appears promising for development of medium-term bioassay systems for detection of environmental carcinogens.

Animals↗
PubMed1988

Dose-dependent induction of liver and thyroid neoplastic lesions by short-term administration of 2-amino-3-methylimidazo[4,5-f]quinoline combined with partial hepatectomy followed by phenobarbital or low dose 3'-methyl-4-dimethylaminoazobenzene promotion.

Dietary administration of 0.1, 0.05, or 0.025% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for two weeks combined with partial hepatectomy at the end of the first week and followed by long-term treatment with phenobarbital (PB) or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) from week 3 to week 86 resulted in dose-dependent development of liver and thyroid neoplastic and preneoplastic lesions. Quantitation of glutathione S-transferase placental form (GST-P)-positive hepatocellular focal populations revealed a significant correlation of IQ concentration with lesion area, with a yield approximately equal to that generated by a similar dose of 2-acetylaminofluorene. The fact that IQ was less toxic therefore allowed greater yields of hepatocellular carcinomas to be induced. The development of thyroid tumors initiated by the IQ treatment was significantly enhanced by the administration of PB, whereas Zymbal gland tumors induced by IQ did not show any correlation with either PB or 3'-Me-DAB treatment.

2-Acetylaminofluorene↗
PubMed1988

Meningiomas and hemorrhagic diathesis.

The physical act of operating on 13 patients with meningiomas was studied for its effect on the fibrinolytic system. Fibrinolytic abnormalities, mainly due to an increase of plasma fibrinolytic activity, appeared in three patients prior to, during, or after surgery. These patients demonstrated hemorrhagic diathesis in the operative wounds which was associated with a consumptive coagulopathy, namely, an increase of fibrin/fibrinogen degradation product concentration and a decrease of fibrinogen concentration in plasma. Antiplasmin agents (gabexate and tranexamic acid) were effective in minimizing loss of blood during and after the operation. Abnormal hyperfibrinolysis seems to play a role in hemostatic difficulties in patients undergoing surgery for meningioma.

Adult↗
PubMed1988

Detection of amplified N-myc gene in neuroblastoma by in situ hybridization using the single-step silver enhancement method.

Amplification of the N-myc oncogene in 27 cases of neuroblastoma group tumor was examined by in situ hybridization using the single-step silver enhancement technique. The N-myc gene copy numbers of these neuroblastoma group tumors were previously examined by dot-blot hybridization using DNA extracted from formalin-fixed, paraffin-embedded tissues (H Tsuda et al., Lab Invest, 59:321, 1988). Silver grains were deposited just over the nuclei of tumor cells, but no or only faint deposition was observed over those of infiltrating lymphocytes, stromal fibroblasts, and endothelial cells. We judged a case to be positive for gene amplification when silver grains precipitated over the nuclei of the tumor cells to a greater extent than over nuclei of lymphocytes or endothelial cells in the same section. According to this criterion, 14 cases (12 cases of neuroblastoma and 2 cases of ganglioneuroblastoma) were positive for N-myc gene amplification of 27 cases (18 cases of neuroblastoma, 5 cases of ganglioneuroblastoma, and 4 cases of composite ganglioneuroblastoma). These results corresponded well to those of the dot-blot hybridization analysis using the same materials. Thirteen of 15 cases that carried 4 copies or more of N-myc gene were judged positive, and 11 of 12 cases that carried less than 4 copies of the N-myc gene were judged negative by in situ hybridization. In neuroblastoma group tumors with amplification of the N-myc gene, tumor cells were stained almost homogenously, except for two cases of ganglioneuroblastoma, in which less differentiated small round tumor cells were stained more intensely than differentiated ganglion-like cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1988

Retrospective study on amplification of N-myc and c-myc genes in pediatric solid tumors and its association with prognosis and tumor differentiation.

DNA was extracted from formalin-fixed and paraffin-embedded tissues of 85 patients with pediatric malignant solid tumors which had been resected at surgery or obtained at autopsy during a 24-year period. The tumors examined included 25 rhabdomyosarcomas, 12 Wilms' tumors, 10 hepatoblastomas and 37 neuroblastoma group tumors. Neuroblastoma group tumors were subclassified into 25 neuroblastomas and 12 ganglioneuroblastomas among which 6 composite ganglioneuroblastomas were included. Sample blocks were selected from both tumors and normal tissues in the majority of cases. We were able to reliably detect N- and c-myc gene amplification in tumor DNA by dot blot-hybridization. The N-myc gene showed approximately from 3- to 500-fold amplification in 19 of 33 cases of stage IV neuroblastoma group tumor. All of these 33 patients had been intensively treated with chemotherapy and/or radiotherapy. The c-myc was amplified 8-fold in 1 case of rhabdomyosarcoma, but neither N-myc nor c-myc was amplified in any cases of Wilms' tumor or hepatoblastoma. We retrospectively examined the association among N-myc gene amplification, prognosis, and histologic subtype in 33 patients with stage IV neuroblastoma group tumors. The survival of the patients with N-myc gene amplification was shorter than that of the patients without amplification of N-myc (p less than 0.05). There was no significant difference in prognosis between the 2 histologic subtypes; neuroblastoma and ganglioneuroblastoma, and the cases of tumors with amplified N-myc showed shorter survivals for each subtype (p less than 0.05). In every case of neuroblastoma group tumor, the copy number of the N-myc gene was the same among primary site and multiple metastatic tumors, even when the lesions showed differences in histologic subtype like neuroblastoma and ganglioneuroblastoma.

Child↗
PubMed1987

Induction of granulocyte-macrophage colony-stimulating factor by lipopolysaccharide and anti-immunoglobulin M-stimulated murine B cell lines.

The present study was undertaken to elucidate whether B cell lymphoma and hybridoma cell lines can be stimulated by lipopolysaccharides (LPS) or by antibodies against immunoglobulin M (IgM) to produce granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF activity was assayed on the basophil/mast cell line PT-18 which is GM-CSF- and interleukin 3-dependent. Antibodies against murine recombinant GM-CSF were used to identify the colony-stimulating factor activity present in the supernatants of the stimulated B cell lines. When these cell lines were stimulated with LPS, two of five lymphoma and five of six hybridoma lines produced GM-CSF. Two cell lines, the B cell lymphoma M12.4.1 and the hybridoma TH2.2, were analyzed more extensively under serum-free conditions. In these two cell lines, the production of GM-CSF was dependent on the dose of LPS used and time of exposure. Antibodies against IgM stimulated the TH2.2 (IgM+) but not the M12.4.1 (IgM-) cells to produce GM-CSF. Northern blot analysis of the M12.4.1 and TH2.2 cells showed that mRNA of GM-CSF can be detected in LPS-stimulated but not in unstimulated cells. Our data show that transformed B cells can be stimulated to produce GM-CSF. The present data and previous studies on GM-CSF production by normal bone marrow-derived B cells suggest a possible participation of B cells in granulopoiesis.

Animals↗
PubMed1987

Compared promoting potential of D-galactosamine, carbon tetrachloride and partial hepatectomy in rapid induction of preneoplastic liver lesions in the rat.

Effectiveness of two different chemically induced stimuli for hepatocellular proliferation was compared with regard to that of commonly used partial hepatectomy (PH), for the purpose of developing short-term protocol for the assay of promoting agents of hepatocarcinogenesis. Enhancing effect of D-galactosamine (DGA) and carbon tetrachloride (CCl4) given during the promotion procedure by 2-acetylaminofluorene (2-AAF) was compared along with PH in rats initiated by diethylnitrosamine (DEN), using preneoplastic glutathione S-transferase positive (GST-P+) hepatocyte foci as an end-point marker lesion. The number of GST-P+ foci per cm2 was largest in the group given CCl4 followed by DGA, no treatment (2-AAF alone) and PH. In contrast, the area (mm2) per cm2 and mean diameter of the focus were largest in the PH group then DGA followed by CCl4 and no treatment. The results indicate that the number of GST-P+ foci were not clearly affected by 3 different treatments whereas area and size of foci which represented the result of promoting effect were clearly influenced by those treatments, indicating they caused differential proliferation of initiated cells. In this respect, even though PH is the most potent procedure, DGA is also efficient and preferred to CCl4 for the non-surgical enhancing method.

Animals↗
PubMed1987

The expression of functional erythropoietin receptors on an interleukin-3 dependent cell line.

We report the expression of the erythropoietin receptors on an interleukin-3 dependent cell line. By the transfer into medium supplemented with erythropoietin, DA-1 cells were converted to an erythropoietin dependent growth state. [125I] erythropoietin was used to detect receptors specific for this hormone on the cell surface. Binding studies revealed that erythropoietin bound to 131 +/- 23 receptors/cell with a Kd of 0.54 +/- 0.2 nM. When the cells were incubated at 37 degrees C, trichloroacetic acid soluble radioactivity appeared in the medium after [125I] erythropoietin binding began to decrease, suggesting that the decline represents the degradation of cell associated [125I] erythropoietin- receptor complexes.

Cell Line↗
PubMed1987

T-cell acute lymphoblastic leukemia relapsing as acute myelomonocytic leukemia and terminating possibly as chronic myelocytic leukemia.

A 9-year-old boy suffering from T-cell acute lymphoblastic leukemia (T-ALL) with a mediastinal mass had a complete remission as a result of treatment. Ten months later, he developed a typical acute myelomonocytic leukemia (AMMoL) pattern. Two months after a second relapse, he showed a clinical picture that was indistinguishable from chronic myelocytic leukemia (CML). At autopsy, massive infiltration of CML-like cells was observed even in the thymus (190 g). These observations suggest that the leukemia in this child arose in a pluripotent stem cell capable of differentiation into both T-lymphocytic and myelomonocytic lineages.

Antibodies, Monoclonal↗
PubMed1987

Hamartoma of the parotid gland: a case report with immunohistochemical and electron microscopic study.

A case of a solid parotid tumour in a 16-year-old boy is presented. Histologically, the tumour demonstrated some peculiar findings. An acinar pattern was predominant although every component seen in the normal salivary gland was present, namely, serous and mucous gland acini, ducts, myoepithelial cells, adipose and lymphoid tissue. Large eosinophilic granules were abundant in the large acinar cell cytoplasm. Immunohistochemically, the tumour demonstrated the proteins which are present in the normal parotid gland, for example, amylase, lactoferrin and lysozyme. Electron microscopic features were quite similar to those of normal parotid tissue except for accumulation of a large number of cytoplasmic granules in the acinar cells. There has been no previous report of a tumour with the same features as seen in this case. Our pathological diagnosis is hamartoma, although the possibility of hyperplasia or neoplasia can not be excluded.

Adolescent↗