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Biomedical subjects

N Takeichi

Publications and source records attributed to N Takeichi.

At least 127 records · Page 7Linked to original sources
PubMed1989

[Experimental approach to the investigation of tumor progression].

We investigated the effects of host inflammatory cells on the progression of QR (C57BL/6 mouse) and ER (SHR rat) regressor tumor cells which spontaneously regress in normal syngeneic hosts. We noted an enhanced tumorigenicity of regressor tumor cells after s.c. implantation with attachment to plastic plate, a situation which induces inflammation in normal hosts accompanied by the development of tumors as compared to normal mice injected with regressor tumor cells in suspension in PBS- which spontaneously regressed. We also observed enhanced tumorigenicity of regressor tumor cells injected into the site of the plastic plate which had been previously implanted into the normal host. Regarding these phenomena, we suggest that tumor progression may be induced by host induced inflammatory cells or their products. We also found enhanced tumor progression of QR regressor tumor cells after co-inoculation with inflammatory cells produced by the implantation of hemostatic spongel into the peritoneal cavity of mice. The mechanisms involved in the progression of regressor tumor cells by co-existence with inflammatory cells are thought to be associated with the production of oxygen radicals, tumor cell chemotactic factors, soft agar colony promoting factors and PGE2.

Animals↗
PubMed1989

X-ray-induced mutations in cultured human thyroid cells.

Cultured human thyroid cells were X-irradiated in vitro and assayed for resistance to 6-thioguanine. The average mutant frequency was 1.69 +/- 1.34 X 10(-5) (mean +/- SD) in controls, 3.74 +/- 2.21 X 10(-5) in cells exposed to 1 Gy, and 7.19 +/- 5.37 X 10(-5) in cells exposed to 2 Gy. The positive association between mutant frequency and dose was statistically significant. The estimated mutation induction rate was 2.54 +/- 0.71 X 10(-5) per gray, which is in close agreement with published results for human skin fibroblasts and mammary epithelial cells. These results extend and confirm earlier reports that mutation induction rates for fibroblasts and epithelial cells after exposure to X rays are similar.

Adult↗
PubMed1989

[Pathogenesis of spontaneous hepatitis in an inbred strain of LEC (Long Evans cinnamon) rats].

We have reported an inbred strain LEC rats with high frequency of spontaneous hepatitis. In this paper, we study a possible involvement of hepatitis virus, hereditary background, and correlation between serum IgG level and onset of hepatitis in LEC rats. Neither electron microscopy nor indirect immunofluorescent test could detect hepatitis virus article or antigen. Furthermore, we could not succeed in inducing hepatitis of LEA and WKA/H rats by injecting the serum, plasma and liver homogenates of the affected IEC rats, nor in promoting/developing hepatitis of LEC and LEA rats under the immunosuppressed condition by administration of steroid hormone. When we made a mating between LEC and non-hepatitis rats to investigate the hereditary mode, F1s had no hepatitis, but F2s and backcrosses developed hepatitis. We observed, in particular, the lower the serum IgG level was, the higher the rate of developing hepatitis was. From these results, we speculate that the involvement of hepatitis virus is not likely, but that a genetic mutation might cause low level of IgG and be also correlated with development of hepatitis.

Animals↗
PubMed1989

[Combined immunodeficiency in LEC (Long Evans Cinnamon) rats with spontaneous hepatitis].

We investigated LEC rats immunopathologically which spontaneously developed hepatitis to find out the genesis, in comparison with non-hepatitis LEA (Long Evans Agouti) rats. 1) Wet weights of the spleen and thymus of 6-week old LEC rats were significantly lighter than those of LEA rats of the same age. 2) Serum IgG (Immunoglobulin G) in LEC rats remained markedly low after the age of two months and IgG antibody formation to SRBC (Sheep Red Blood Cell) as detected by plaque assay was also significantly suppressed. On the other hand, IgM antibody formation to SRBC was significantly suppressed through serum IgM level in LEC rats was normal or rather increased. 3) Blastogenic responses of spleen cells to PHA and Con A were much more suppressed in LEC rats than in LEA rats. 4) Cytostatic activity of intraperitoneal macrophages against tumor cells was more evident in LEC rats than in LEA rats, but there was no difference in NK (natural killer) activity between the two rat strains. From these results, it is speculated that spontaneously hepatitis-developing LEC rats possess T and B cell deficiency (combined immunodeficiency) and that the increase of macrophage and NK cell activities are linked to the genesis of developing hepatitis.

Animals↗
PubMed1988

Metastatic capacity and intercellular communication between normal cells and metastatic cell clones derived from a rat mammary carcinoma.

Three highly metastatic clones and two weakly metastatic clones were obtained from a spontaneously arising mammary carcinoma in an SHR rat. The difference in their capacity to generate metastatic ability was recognized when the tumor cells were implanted s.c. but not when they were implanted i.v. This evidence possibly indicates that the difference in the metastatic capacity of these clones is caused by different potential for detachment from the primary site and for intravasation during the various steps of metastasis. There are no differences between highly and weakly metastatic clones with regard to their in vitro growth characteristics (doubling time, saturation density, plating efficiency, etc.), homotypic aggregation, and adhesiveness to plastic matrices and fibroblast monolayers. Therefore, we used a dye transfer method to examine the relationship between the metastatic capacity of tumor cells and the capacity of tumor cells to make junctional communication with normal fibroblasts. We found that the incidence of intercellular communication between weakly metastatic clone cells and fibroblasts (derived from normal s.c. tissues and tumor tissues) was significantly higher than that between highly metastatic clone cells and fibroblasts. These results suggest that junctional communication between tumor cells and normal fibroblasts may play a part in the early stage of cancer metastasis.

Animals↗
PubMed1988

Modification of regression of virally xenogenized tumor cells by cyclophosphamide and busulfan.

Rat fibrosarcoma cells infected with Friend leukemia virus (FV-KMT-17) grow for a short time and then regress spontaneously in syngeneic hosts. This regression mechanism was examined by analyzing the immunomodulating action of the antitumor drugs busulfan (BU) and cyclophosphamide (CY). In preliminary experiments, the optimum dosages of BU and CY for the enhancement of DTH responses to SRBC were 10 mg/kg and 40 mg/kg respectively. Treatment of rats with BU (10 mg/kg) on day 5 induced the regression of KMT-17 cells, while in contrast, the same drug delayed the spontaneous regression of FV-KMT-17 cells. Pretreatment with CY (40 mg/kg) on day 5 did not affect the growth of KMT-17 or FV-KMT-17 cells. After the same treatment schedule, BU inhibited humoral antibody formation against SRBC and against virus-associated antigen (VAA), NK cell activity, and ADCC effector cell activity. On the other hand, CY did not affect the activities of NK cells or ADCC effector cells, although it significantly augmented the DTH responses to SRBC and the production of antibody to VAA but had no effect on production of antibodies to SRBC. These results suggest that NK cells and ADCC may play an important role in the initial stage of the spontaneous regression of FV-KMT-17 cells.

Animals↗
PubMed1988

Hematopoietic growth factors (BPA and Epo) induce the expressions of c-myc and c-fos proto-oncogenes in normal human erythroid progenitors.

We investigated serial expressions of eight proto-oncogenes during in-vitro differentiation of normal human burst-forming unit, erythroid (BFU-E), and found that c-myc and c-fos are expressed in progenies of BFU-E. The expressions of the two proto-oncogenes correlated to the replating efficiency and adversely to erythroid differentiation. The absence of hematopoietic growth factors decreased the expressions, but the addition of erythropoietin together with burst promoting activity induced a re-expression of the c-myc and c-fos after 2 h of incubation. These observations suggest that the c-myc and c-fos proto-oncogenes have a physiological role in the proliferation of erythroid progenitors and that activations of the two proto-oncogenes are early cellular events after the stimulation by hematopoietic growth factors.

Cell Differentiation↗
PubMed1988

Metabolic predisposition of a novel mutant (LEC rats) to hereditary hepatitis and hepatoma: alterations of the drug metabolizing enzymes.

Previously we established that 'LEC rats' have displayed spontaneous fulminant hepatitis with severe jaundice, which progressed to liver cancer, and a single autosomal recessive gene is responsible for the cause of the diseases. The activities of drug metabolizing enzymes were assayed in livers from LEC and control (LEA) rats at 4 weeks and 3 months before the onset of liver cancer. At 4 weeks the cytochrome P-450 content of the LEC rat livers was 43% of the control (LEA) value. At 3 months the level was 65% of the control. Epoxide hydrolase, gamma-glutamyltranspeptidase and UDP-glucuronyltransferase activities were 2.6-, 6.9- and 2.4-times higher than those in the LEA rats at 4 weeks, respectively, while glutathione S-transferase activity was not significantly different between the two strains. The enzyme changes in the LEC rats are quite similar to those observed in hyperplastic foci and nodules in chemical carcinogenesis of hepatocytes.

Animals↗
PubMed1988

Depression of T cell-mediated immunity and enhancement of autoantibody production by natural infection with microorganisms in spontaneously hypertensive rats (SHR).

We studied the effects of breeding conditions on the development of immunological abnormalities in spontaneously hypertensive rats (SHR) with congenital T cell depression. The depression of T cell functions, the production of natural thymocytotoxic autoantibody (NTA), and the development of polyarteritis nodosa were more evident in SHR reared under a conventional (CV) environment than in specific-pathogen-free (SPF) SHR bred in a semi-barrier system. Enhancement of these immunologic abnormalities was also observed by the conventionalization of SPF-SHR. A high frequency of antibodies to mouse hepatitis virus (MHV), Sendai virus, and Mycoplasma pulmonis was detected in CV rat sera, whereas no antibodies were detected in SPF-SHR. The experimental infection of Sendai virus induced the enhancement of T cell depression and of NTA production in SPF-SHR. We interpret these results to mean that the natural infection of microorganisms causes an acceleration of immunologic abnormalities in SHR reared in a CV environment.

Animals↗
PubMed1988

Xenogenization of tumor cells by transfection with plasmid containing env gene of Friend leukemia virus.

A rat hepatocellular carcinoma cell line (cKDH-8 cl-11) showed decreased tumorigenicity after transfection with an envelope gene derived from a Friend leukemia virus (FV-env gene). FV-env gene product was found by indirect immunofluorescence staining to be expressed on the cell surface of the FV-env gene-transfected cells. The FV-env-transfected cells (FV-env cKDH-8), however, grew well in X-irradiated immunosuppressed rats, indicating that the reduction in tumorigenicity of the transfected cells is based on immunological reaction in the host. The rats which rejected FV-env cKDH-8 cells showed resistance to rechallenge with the parent cKDH-8 cl-11 tumor cells. These results suggest that the FV-env gene product may elicit antitumor immunity against FV-env cKDH-8 cells in a host with a resultant reduction in the tumorigenicity of these cells.

Animals↗
PubMed1988

Spontaneous hepatitis in Long-Evans rats. A potential animal model for fulminant hepatitis in man.

Spontaneous hepatitis associated with severe jaundice occurred in 90% of an inbred strain of Long-Evans rats. The rapidly progressive syndrome was characterized by abrupt onset, hyperbilirubinemia and increased serum levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, associated with massive and multifocal necrosis of the liver. This strain should provide a useful animal model for analysis of the pathogenesis of fulminant hepatitis in humans.

Alanine Transaminase↗
PubMed1988

Regulation of erythropoietin and burst-promoting activity production in patients with aplastic anemia and iron deficiency anemia.

To clarify the control mechanism of production of erythropoietic growth factors in anemic states, we compared erythropoietin (Epo) and burst-promoting activity (BPA) in patients with aplastic anemia and iron deficiency anemia, using in vitro erythroid progenitor assays. Although serum levels of Epo activity increased in the presence of anemia, the rise was more marked in patients with aplastic anemia. BPA was high only in the sera of aplastic anemia patients. Serum levels of BPA of patients with aplastic anemia negatively correlated with hemoglobin concentrations, while those of patients with iron deficiency anemia did not correlate. In 2 patients with aplastic anemia who responded well to androgen therapy, serum levels of Epo activity and BPA decreased after the hemopoiesis had recovered. These results suggest that serum levels of BPA do not rise in response to anemia only. The elevated BPA levels in sera in cases of aplastic anemia are probably related to a reduction in the number of hemopoietic stem cells. Moreover, we observed that BPA in bone-marrow-conditioned medium (BMCM) from patients with severe aplastic anemia increased more than in the BMCM from patients with severe iron deficiency anemia. Therefore, our findings suggest that the enhanced BPA production depends on a decrease in hemopoietic precursors rather than the anemic state.

Adolescent↗
PubMed1988

Delayed hypersensitivity reactions to virus-augmented syngeneic and allogeneic tumor associated antigens.

Delayed hypersensitivity (DH) reactions to intact MSV-induced tumor cells or their crude membranes (CM) were studied across the H-2 histocompatibility barrier, using the radioisotopic footpad assay. Allogeneic as well as syngeneic tumor cells or their CM produced significant DH reactions in MSV-immune mice. CM from these cells after infection with influenza virus induced a stronger tumor-specific DH reaction in immune mice than did CM from uninfected cells. These results indicate that H-2 histocompatibility is not always required for induction of a cell-mediated immune response to tumor associated antigens and support the feasibility of a tumor specific skin test in humans using CM of autologous or allogeneic cultured human tumor cells.

Animals↗
PubMed1988

[Malignant lymphoma of the thyroid gland].

During the past 14 years, 14 cases involving a malignant lymphoma of the thyroid have been treated at our department. These cases have been histologically reviewed and reclassified, according to the Working Formulation. Four cases involved a low grade malignancy (LGM), 9 cases an intermediate malignancy (IGM), and 4 cases a high grade malignancy (HGM). Thirteen lymphomas were of the B-cell type, and the remaining lymphoma was of the T-cell type. The coexistence of a chronic thyroiditis was noted in 9 cases. Survivors were only found in the LGM and IGM groups. We consider it necessary to treat malignant lymphomas of the thyroid according to the subtype of the Working Formulation.

Aged↗
PubMed1988

[Inhibitory effect of UFT on postoperative lung metastasis of mammary adenocarcinoma in SHR rats].

It is well known that UFT has significant therapeutic effects against experimental and clinical cancers at the primary sites. In this experiment, we studied the inhibitory effect of UFT on the lung metastasis of spontaneously developed rat mammary carcinoma (SST-2) after surgical excision of the primary site. In comparison of UFT-treated (15 or 30 mg/kg/day) with 5-FU-treated (9.7 or 19.5 mg/kg/day) groups, UFT was more effective than 5-FU in the antitumor activity and the inhibitory effect of lung metastasis with/without surgical excision of the primary sites. Rats (5-10 rats per group) were inoculated s.c. with 1 x 10(6) SST-2 cells and administered with UFT orally (15, 30 or 60 mg/kg/day) starting the day after tumor inoculation for 30 days. The therapeutic effect of UFT was studied by the growth rate of primary tumor and the numbers of metastatic colonies in the lung 35 days after tumor inoculation, comparing the UFT-treated with control groups. UFT administration at the doses of 30 or 60 mg/kg/day markedly inhibited the growth of the primary tumors and the number of metastatic lung colonies decreased, compared with that of the control group. However, in the group of rats treated at the dose of 60 mg/kg/day, 60% of rats died from the side effects of UFT such as weight loss, hemorrhage etc. In all groups in which the primary tumors were surgically excised 20 days after tumor inoculation and then treated with UFT (15, 20 or 30 mg/kg/day), we observed marked prolongation of survival period and inhibition of lung metastasis as well. Furthermore, we studied the effect of combination therapy of UFT and lentinan (1 mg/kg/day i.p.) on the metastasis of SST-2 cells after surgical excision of the primary sites. It was more effective than UFT alone. Thus, it is clear that UFT is an effective anticancer drug to inhibit metastasis of tumors in the lung after surgical excision of primary tumor.

Adenocarcinoma↗
PubMed1987

Age-related changes of natural antitumor resistance in spontaneously hypertensive rats with T-cell depression.

We investigated the relationship between age-related changes in natural resistance and antitumor effects using a spontaneously hypertensive rat (SHR rat) strain which shows a progressive decline of the number of T-cells and their functions as a result of aging. The growth of a weakly antigenic mammary adenocarcinoma SST-2 was significantly suppressed in SHR rats ages 2 and 3 months, whereas in SHR rats ages 1 or 8 months no suppression of the tumor growth was observed. Splenic natural killer cell activity among the SHR rats was still low at 1 month, when the T-cell function is relatively intact; it reached a maximum level at 3 months and thereafter rapidly decreased. On the other hand, the cytostatic activity of peritoneal macrophages, which is also low at 1 month and becomes high at 3 months, thereafter remained at high levels until 8 months of age. That is, the kinetics of natural killer cell activity during the aging processes runs parallel to the function of suppressing tumor growth. Treatment with anti-asialomonoganglioside antiserum abrogated the suppressive activity of SST-2 tumor growth in 3-month-old SHR rats. Treatment with double stranded RNA polyinosinate-polycytidylate, an interferon inducer, produced significant suppression of the tumor growth in SHR rats ages 3 and 8 months. These results suggest that the participation of natural killer cells is a principal effector mechanism in the suppression of SST-2 tumor growth in SHR rats ages 2 and 3 months.

Aging↗