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Biomedical subjects

N Takeichi

Publications and source records attributed to N Takeichi.

At least 109 records · Page 6Linked to original sources

Parathyroid tumors in atomic bomb survivors in Hiroshima: first report of surgical cases, 1956-1988.

Seventeen patients with parathyroid gland tumors underwent surgical resection at the Hiroshima University Hospital between 1956 and 1988. Three of them where born after the atomic bomb explosion, and 6 of the remaining 14 patients (42.9% of the total- a high proportion) were atomic bomb survivors. Because parathyroid gland tumors and hyperparathyroidism are assumed to develop in patients who have been exposed to radiation after a long latent period, it is necessary to anticipate the possible occurrence of these diseases in atomic bomb survivors. The present paper is the first to report surgically extirpated parathyroid gland tumors in atomic bomb survivors.

Adolescent↗

Junctional communication of highly and weakly metastatic variant clones from a rat mammary carcinoma in primary and metastatic sites.

We have investigated junctional intercellular communication (JC) in primary and metastatic sites, using two highly and two weakly metastatic variant clones which had been isolated from a rat mammary carcinoma cell line, c-SST-2. After each variant had been subcutaneously inoculated into syngeneic rats, tumor cells were isolated from local tumor (primary tumor) and their metastatic foci (lung, heart and kidney). The cells were then recultured, and we measured their JC in vitro by the dye transfer method with the fluorescent dye Lucifer yellow CH, and found that the homologous (tumor cell-tumor cell) JC of highly metastatic clones were less in recultured tumor cells from primary tumors than that of weakly metastatic clones. At the same time, the heterologous (tumor cell-normal fibroblast) JC of highly metastatic clones was less than that shown by weakly metastatic clones. On the other hand, tumor cells obtained from metastatic foci showed relatively reduced JC (homologous and heterologous) when compared with those from their primary tumors in the weakly metastatic clones. These data suggest that a decrease in and/or a loss of JC may play a role in the expression of metastatic properties.

Animals↗

Effects of sex difference, gonadectomy, and estrogen on N-methyl-N-nitrosourea induced rat thyroid tumors.

The occurrence of thyroid tumors induced by N-methyl-N-nitrosourea (MNU) and low iodine diet in Long-Evans (LE) rats was studied with special reference to sex difference, effect of gonadectomy, and estradiol administration. Rats of experimental groups 1-6 were given i.v. injections of 40 mg of MNU/kg of body weight at 50 days of age and fed on low iodine diet from 28 days of age to the end of the experiment (30 weeks after MNU administration). They consisted of male, female, castrated male, ovariectomized female, and gonadectomized male and female rats given 2.5 mg estradiol pellets s.c. Rats of groups 7-10 served as the respective controls without MNU or low iodine diet. Levels of serum thyroid stimulating hormone and estrogen receptor of the thyroid lesions were also examined. It was noted that the incidence of thyroid carcinoma was higher in females than in males (P less than 0.01) and did not change by castration in males but decreased in ovariectomized rats (P less than 0.01). Administration of estradiol after gonadectomy significantly increased the incidence of thyroid carcinomas in castrated and ovariectomized rats. Increase of mean serum thyroid stimulating hormone levels and thyroid and pituitary weights was also predominant in females. Mean thyroid stimulating hormone levels of both sexes were decreased by gonadectomy. Mean thyroid and pituitary weights were inhibited from increasing not by castration but by ovariectomy. Estradiol supplemented after gonadectomy significantly increased all of these factors. Estrogen receptors were detected in transplanted thyroid tumors but not in euthyroid tissues. The results suggest that estradiol promoted the thyroid tumorigenesis through activation of thyrotrophs in pituitary or direct interaction of estradiol and estrogen receptors in the thyroid.

Animals↗

Ultrastructural differences in junctional intercellular communication between highly and weakly metastatic clones derived from rat mammary carcinoma.

We examined by electron microscopy the differences in junctional intercellular communications among highly metastatic clones, weakly metastatic clones, and the parent clone obtained from a spontaneously developed rat mammary carcinoma. We also investigated intercellular communications of the highly and weakly metastatic clone cells with normal fibroblasts. The results showed that ultrastructural changes of the highly metastatic clone cells, such as microvilli, microfilaments, and small organelles including endoplasmic reticulum, Golgi apparatus, and mucous particles, were more distinct than those of the weakly metastatic clone cells, and that the numbers of desmosome and gap junctions of weakly metastatic clone cells were significantly greater than those of highly metastatic clone cells. The formation of gap junctions and desmosomes was found only between weakly metastatic clone cells and normal fibroblasts. When both highly and weakly metastatic clone cells were cultured with normal fibroblasts, a tight junction was observed only in the culture of weakly metastatic clone cells and normal fibroblasts. These results suggest that ultrastructural differences are related to the proliferation and detachment of tumor cells from the primary site in the initial stage of tumor metastasis.

Animals↗

Age-related decrease of pulmonary metastasis of rat mammary carcinoma by activated natural resistance.

We found that the number of pulmonary metastatic foci of spontaneously developed rat mammary carcinoma (SST-2), when transplanted subcutaneously in spontaneously hypertensive (SH) rats, decreased with aging. In the SST-2-bearing SH rats, it was observed that T cell functions progressively declined while activities of macrophages and natural killer cells were non-specifically activated by increasing age. To examine the mechanisms of the age-related decrease of pulmonary metastasis in SH rats, we treated the SST-2-bearing rats with anti-(asialo-GM1) antibody and/or carrageenan, which are known to suppress the functions of macrophages and natural killer cells, or with poly(I).poly(C), which is a stimulator to natural killer cells. The anti-(asialo-GM1) treatment significantly increased the number of pulmonary metastatic foci in both young and old SH rats, while poly(I).poly(C) significantly decreased the lung nodules in the old SH rats. These result suggest that the decrease of pulmonary metastasis in the SH rats with aging may be closely correlated with non-specifically activated natural killer cells and macrophages, though it should be also considered that non-immunological tumor-host interactions may be involved in the differences between the young and the old SH rats.

Aging↗

Increased expression of c-jun gene during spontaneous hepatocarcinogenesis in LEC rats.

We have studied the expressions of nine proto-oncogenes (c-myc, N-myc, c-fos, C-jun, p53, H-ras, N-ras, c-raf, hst) and two other genes (PCNA, GST-P) during the spontaneous development of hepatocellular carcinomas (HCCs) in LEC rats. Expression of c-myc, H-ras, N-ras, C-raf, p53 and PCNA genes was detected, but this did not significantly change during the development of HCCs in LEC rats. Expression of N-myc and hst genes was not detectable. Expression of c-fos gene was detected in one HCC case out of four. Significantly increased expression of c-jun gene was observed in the liver tissues of LEC rats aged 8 months. This high expression was decreased with the development of HCCs. On the other hand, the expression of GST-P gene increased in parallel with the clinical course of the development of HCCs in LEC rats. The pattern of c-jun mRNA augmentation was different from that of GST-P mRNA. These observations suggest that c-jun gene may play a role in the spontaneous development of HCCs in LEC rats.

Age Factors↗

Correlation between the presence of microvilli and the growth or metastatic potential of tumor cells.

We used an electron microscope to examine microvilli which appear on the surfaces of various tumor cells with high or low growth potential and/or metastatic ability. The results show that a greater number of microvilli appeared on the surfaces of tumor cells (QRpP and ERpP) which possess high growth potential than on tumor cells (QR and ER) with low growth potential. We also observed that microvilli were more abundant on the surface of highly metastatic clone cells, i.e. c-SST-2 (cl-2), mouse B16 melanoma (F-10) and human colon carcinoma (KM12SM) than on weakly metastatic clone cells, c-SST-2 (cl-4-2), B16 (F-1) and (KM12C). At the same time, more microvilli were observed on the surface of B16 BL6 cells, which were obtained from the metastatic site of the B16 F10 cells, than on the surface of the parent B16 F10 cells. Immunoelectron microscopy revealed that the c-neu oncogene product, which is closely related to an epidermal growth factor receptor, was positively stained in the microvilli of tumor cells (ERpP) with high growth potential and high metastatic ability, whereas the tumor cells (ER) with low growth potential and weak metastatic ability were not stained. These findings suggest that the increased presence of microvilli correlates closely with the growth potential and metastatic ability of tumor cells.

Animals↗

Diffuse sclerosing variant of papillary carcinoma of the thyroid. A histopathological study of four cases.

We present four cases of an unusual diffuse sclerosing variant of papillary carcinoma of the thyroid occurring in Japanese women ranging in age from 17 to 42 years. Macroscopically, both lobes of the thyroid were involved, being diffusely enlarged and firm. Histologically, the tumor was characterized by squamous metaplasia of tumor cells, numerous psammoma bodies, extensive stromal fibrosis, severe lymphocytic infiltration with formation of lymph follicles, and thin bundles of smooth muscle cells in the fibrous stroma. The tumor islands were located mainly within the dilated lymphatic vessels and the metastatic tumor involved the bilateral cervical lymph nodes in all cases. It is assumed that papillary carcinoma of this type invades the thyroid lymphatics during the early stage and, without forming nodular lesions, disseminates to both lobes with extensive metastasis to the cervical lymph nodes. It should be noted that papillary carcinoma of this type often suggests chronic thyroiditis clinically because of the symmetrical enlargement of the thyroid and frequent positive anti-thyroid antibodies in the serum. Some workers have reported the prognosis to be unfavorable because of extensive lymphatic involvement, but the prognosis of this variant has not yet been defined.

Adolescent↗

[An immunohistochemical study of estrogen receptors in thyroid carcinoma].

Estrogen receptors immunoreactivity (ER-IR) has been examined in 64 cases of human thyroid carcinomas. ER-IR was found to be located in the nucleus of cancer cells and was detected in 30 (57.7%) of 52 papillary carcinomas that were examined. Eleven cases showing a good number of ER-IR positive cancer cells revealed a lowered EORTC index of under 65, and no ER-IR was found in 12 anaplastic carcinomas. These findings indicate that ER-IR might generally bear a similar reciprocal relationship to the malignancy of a thyroid carcinoma.

Adult↗

Growth-associated shedding of a tumor antigen (CE7) detected by a monoclonal antibody.

A monoclonal antibody was developed against an antigen, termed CE7, which was highly expressed on the surface of rat fibrosarcoma KMT-17 cells (clone A3) cultured in low serum medium (A3-1% FCS). The CE7 antigen was not detectable on A3 cells cultured in ordinary high serum medium (A3-10% FCS), on in vivo passaged A3 cells, or on parental in vivo KMT-17 cell line. However, immunoelectron microscopy and Western blot analyses indicated that CE7 antigen was produced by these tumor cells in all circumstances but was shed from their surfaces in vesicular form into the surrounding tissue culture medium or ascites, unless low serum concentration prevailed and disappeared from their cell surfaces. We have previously reported that the immunogenicity of A3 cells was increased when the serum concentration was lowered from 10% to 1% and the phenomenon paralleled the CE7 antigen expression on the A3 cells. These results suggest that the CE7 antigen could be a tumor-associated rejection antigen and that the expression of the CE7 antigen on A3-1% FCS cells (which is shed by high serum culture or in vivo transplantation and disappears from the cell surface) may play a role in immunological responses against the tumor cells.

Animals↗

The significance of immunochemically staining calcitonin and CEA in fine-needle aspiration biopsy materials from medullary carcinoma of the thyroid.

A review of ten surgical cases of medullary carcinoma of the thyroid (MCT) demonstrates the usefulness of establishing a preoperative cytological diagnosis through the immunochemical staining of calcitonin (CT) and CEA in fine-needle aspiration (FNA) biopsy smears. If MCT is suspected after routinely performing May-Grünwald-Giemsa stained cytology of an FNA biopsy in the outpatient clinic, then CT and CEA staining is recommended for confirmation of MCT. The advantages of this immunochemical staining include that it can be carried out in the outpatient clinic within one day and also that it is much less costly than measuring serum CT and CEA.

Biopsy, Needle↗

The possible mode of escape of adult T-cell leukaemia cells from antibody-dependent cellular cytotoxicity.

Antibody-dependent cellular cytotoxicity (ADCC) was measured using 51Cr-labelled ATL derived cell lines as the target, peripheral mononuclear cells (PMNCs) from disease-free persons as the effector cells and heat-inactivated serum from patients with ATL or the IgG purified from this. The release of 51Cr was not usually demonstrated in the HTLV-1 non-producing ATL derived cell line (MT-1), but was evident in the HTLV-1 producing ATL derived cell lines (KT 252 and IT 607). The 51Cr-labelled MT-1 cells after induction of HTLV-1 retrovirus by 5-iodo-2'-deoxyuridine (IdUr), showed a remarkable target sensitivity in the ADCC assay. On the other hand, the 51Cr-labelled MT-1 cells after culture with IdUr and ATL patient's serum, had no ADCC sensitivity. The fresh ATL cells immediately separated from ATL patient's blood did not express HTLV-1 virus in the cell and had no ADCC sensitivity as the target. Based on these findings, an antigenic modulation on the ATL cell surface by ATL patient's serum is considered to be the possible mode of escape of ATL cells from ADCC.

Adult↗

Dual rearrangement of immunoglobulin and T-cell receptor genes in blast crisis of CML.

Dual rearrangement of immunoglobulin and T-cell antigen receptor (beta, delta) genes was demonstrated in a case of Philadelphia chromosome-positive chronic myeloid leukemia (CML) in blast crisis. The blast cells, showing L2 morphology and high activity of TdT, expressed pre-B cell (CD19+, Ia+) and myeloid (CD13+, CD34+) surface antigens but lacket T-cell antigens (CD2-, CD7-). Cytogenetic studies on bone marrow and peripheral blood revealed the Phl chromosome in all metaphases analyzed, majority of which also had the additional chromosome changes, +8, +10, +21. Furthermore, molecular analysis of the breakpoint cluster region (bcr) on chromosome 22 showed a rearrangement, confirming the CML origin of the blast cells.

Blast Crisis↗

[Establishment of an inbred strain of LEC (Long Evans Cinnamon) rats with spontaneous hepatitis].

At the Center for Experimental Plants and Animals, Hokkaido University, two inbred strains, Long Evans Cinnamon (LEC) and Long Evans Agouti (LEA), which were selected for coat colour, were isolated from a closed colony of Long Evans rats. While the two inbred strains were maintained by sibmating, only LEC rats, over 24-generation, spontaneously developed acute hepatitis with sudden appearance of systemic jaundice at around four months after birth. The frequency of acute hepatitis was 80 to 90% and the disease in nearly 80% of these rats were progressive and they died within two weeks after onset, with their clinical course and histopathological findings similar to those of human fulminant hepatitis. LEC rats with spontaneous hepatitis had strong-conversion of urine-bilirubin, ultimate increase of blood-bilirubin and abnormal increase of serum-transaminases (GOT, GPT; GOT greater than GPT). Histopathological findings of the livers in the rats with acute hepatitis showed spotty necrosis and abnormal hepatocytes containing giant bizarre nuclei and in the rats with fulminant-type hepatitis showed central or coagulated necrosis and marked infiltration of inflammatory cells. Serum levels of albumin in LEC rats before being affected by hepatitis were low compared with those of LEA rats and especially characteristic fact was that cellulose-acetate electrophoresis could not reveal gamma-globulin fraction in LEC rats of 6-week and 12-week old, which will be a clue to analyze the etiology of hepatitis in LEC rats.

Alanine Transaminase↗

[Timing of UFT administration combined with surgical operation in pulmonary metastasis of rat mammary carcinoma].

We investigated the effective timing of UFT administration combined with surgical operation for inhibiting pulmonary metastasis of spontaneously developed mammary carcinoma (SST-2) which produces 100% pulmonary metastasis in syngeneic rats after s.c. transplantation. Rats (5 rats per group) were inoculated s.c. with 1 X 10(6) SST-2 cells and administered orally with UFT (15, 30 and 60 mg/kg/day) starting 21 days after the tumor inoculation for 2 weeks. UFT at the dose of 30 mg/kg/day was found to be most effective in inhibiting pulmonary metastasis in SHR rats without any noticeable side effects. The rats inoculated s.c. with 5 X 10(4) SST-2 cells were divided into 3 groups: The 1st group was given oral administration of UFT (30 mg/kg/day) starting 7 days before surgical excision of the primary tumor for 2 weeks; 2nd group was treated with UFT starting one day after surgical operation for 2 weeks; and 3rd group was treated with UFT starting 7 days after surgical operation for 2 weeks. The number of lung colonies and survival time were compared among these 3 groups. The results clearly showed that combination of UFT and surgical operation was most effective on the 1st group when compared with the other two groups. UFT therapy, therefore, should be started prior to surgical operation for inhibiting cancer metastasis.

Animals↗

[Impaired superoxide production by neutrophils in myelodysplastic syndrome: correlation with bone marrow karyotype].

Superoxide (O2-) production by neutrophils was examined in 21 patients with myelodysplastic syndrome (MDS), including 13 with primary MDS (p-MDS) and 8 with therapy-related MDS (t-MDS). O2-production of MDS patients was significantly less than that of healthy controls (2.81 +/- 3.51 vs 6.19 +/- 2.41 nmol/min/10(6) PNMs, p less than 0.005). Although no relationship between pathogenesis (primary or therapy related), FAB type and levels of O2- production was observed, O2- production of 11 patients with abnormal bone marrow karyotypes was significantly reduced than that of 10 other patients with normal karyotypes. Furthermore, five t-MDS patients with monosomy for all or part of chromosome no. 7 (-7 or 7q-) showed the lowest level of O2- production, which was significantly different from the level in the patients with other abnormal karyotypes (0.61 +/- 0.29 vs 1.80 +/- 0.31, p less than 0.001). These results suggest that the long arm of chromosome no. 7 may in part play an important role for O2- production by neutrophils.

Adult↗

[Enhancement of cancer growth and metastasis by host reactive cells and their secreting factors].

Proliferation and metastasis of cancer are affected by the interactions between cancer cells and the host cells; in particular, host reactive cells regulate proliferation and metastasis or cancer cells directly through various soluble factors. However, recent studies revealed that cytokines and growth factors released by macrophages and lymphocytes promote proliferation and metastasis of cancer cells, whereas they act for controlling infection or healing wounds. For example, transforming growth factor (TGF) released by lymphocytes and macrophages induces transformation of normal cells to malignant cells; and TGF-alpha promotes the production of PDGF & TGF-beta, which results in the proliferation of cancer cells. It is also known that TGF-beta suppresses proliferation of T.B lymphocytes and production of TNF-alpha. Oxygen radicals are also considered to be involved in the transformation that cancer cells increase their malignancy. This paper will deal with the host-tumor interactions, introducing our experimental results.

Animals↗