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Biomedical subjects

N Takeichi

Publications and source records attributed to N Takeichi.

At least 163 records · Page 9Linked to original sources

The arrest of T cell maturation in spontaneously hypertensive rats with a deficient production of thymic factors.

Spontaneously hypertensive rats (SHR) which regularly develop hypertension and periarteritis nodosa showed a progressive loss of T cell numbers and functions early in life. When six months old and compared with W rats, the original strain of SHR, they were found to possess a reduced number of thymocytes that formed rosettes with guinea pig erythrocytes and that reacted to anti-Thy1. 1 and anti-T (W3/13) sera. The number of spleen and lymph node cells which reacted to anti-T (W3/13) and anti-helper T (W3/25) sera also decreased. The antibody response of 3-month-old SHR spleen cells to SRBC was about one-fifth that of Wistar rats and progressively declined with age. Subcutaneous grafting of 3-month-old SHR thymus tissues failed to promote differentiation and functions of T cells in the spleen of nude mice, whereas 3-month-old W thymus tissues showed significant recovery of T cell generation and functions. The T cell functions of old SHR was completely restored by grafting adult W thymus tissues but was not restored by grafting adult SHR thymus tissues. Similar recovery was also obtained by the injection of thymus extracts from W thymus tissues. These results suggest that thymic epithelial cell products regulating T cell maturation may decrease in SHR with increasing age.

Animals↗

The effect of thymectomy on the development of hypertension in spontaneously hypertensive rats.

We studied the effect of thymectomy on the development of hypertension in spontaneously hypertensive rats (SHR). There were no significant differences between thymectomized and sham thymectomized SHR during either the initial or chronic phase of spontaneous hypertension. Similarly, administration of anti-Thyl. 1 or anti-T sera did not influence the blood pressure in SHR during the chronic phase. The results suggest that the thymus does not play a direct role in the development and maintenance of blood pressure in SHR.

Animals↗

Restoration of T-cell function and induction of antitumor immune response in T-cell-depressed spontaneously hypertensive rats by treatment with thymosin fraction 5.

We studied the effect of treatment with Thymosin Fraction 5 (Fr-5) on the restoration of T-cell functions and the induction of antitumor immunity in spontaneously hypertensive rats (SHR) with congenital T-cell depression. SHR showed a reduced number of rosette-forming thymocytes early in their lives, and in vitro incubation of SHR thymocytes with Fr-5 restored the numbers of rosette-forming T-cells to the normal level for Wistar/HMK rats, the original strain of SHR. In vivo treatment of SHR with various doses of Fr-5 (0.5, 1.0, or 2.0 mg/kg, 6 times every other day) also increased significantly the blastogenic responses of their spleen cells to phytohemagglutinin but failed to promote plaque-forming cell responses to sheep red blood cells. These immunological restorative effects by Fr-5 were dose dependent. In contrast, treatment with lower doses of Fr-5 (0.25 or 0.50 mg/kg) showed greater curative effects on a high antigenic fibrosarcoma (SMT-6) than did treatment with higher doses of Fr-5 (1.0 or 2.0 mg/kg). This was confirmed by the fact that treatment with a 0.5-mg/kg dose of Fr-5 caused a significant suppressive effect on the growth of a weakly antigenic and highly metastatic adenocarcinoma (SST-2) in SHR with a consequent prolongation of survival days, whereas treatment with a 1.0- or 2.0-mg/kg dose of Fr-5 was without any effect. In order to clarify this mechanism, we studied the effect of pretreatment with cyclophosphamide (CY) on the development of antitumor delayed-type hypersensitivity (DTH) reaction in the SMT-6-bearing SHR treated with Fr-5 (0.5 or 2.0 mg/kg). Treatment with 0.5 mg of Fr-5 per kg significantly increased the DTH reaction to SMT-6 cells in both CY-pretreated and untreated SHR. In contrast, treatment with 2.0 mg of Fr-5 per kg produced a significant antitumor DTH reaction in SHR pretreated with CY but failed to induce the DTH reaction in SHR untreated with CY. These results suggest that higher doses of Fr-5 may induce preferentially suppressor T-cells rather than killer T-cells in tumor-bearing SHR with congenital T-cell depression.

Animals↗

[Host defense mechanisms against tumor metastasis].

It is still difficult to control metastasis of cancers, despite advances in surgery and radio-therapy for primary lesions of cancers. The prevention of cancer metastasis is therefore a major target of cancer research. In order to analyse the mechanism of tumor metastasis, several in vivo and in vitro assay systems have been established and the effects of host and tumor factors on formation of tumor metastasis have been studied. It is known that specific immunity mediated by T cells and natural resistance mediated by macrophages and natural killer cells play a significant role in host defense mechanisms against tumor metastasis. I describe here my study of the effect of surgical operation of primary tumors on metastasis and of the suppression of tumor metastasis by activated natural host defense using an experimental model of spontaneous metastasis in spontaneously hypertensive rats (SHR).

Adenocarcinoma↗

Bilateral resection and reconstruction of internal jugular vein for thyroid carcinoma.

Two patients with thyroid carcinoma infiltrating bilateral internal jugular veins were treated. In reconstruction of the internal jugular vein by implantation of an autogenous venous segment or Gore-Tex artificial vessel, the repaired area soon became obstructed. The repaired area with the Impra-Flex artificial vessel became obstructed again one month after the implantation. In the reconstruction by ipsilateral end-to-end anastomosis between the internal and external jugular veins, good circulation was apparent even 2 years after the operation. The internal-external jugular vein anastomosis is expected to increase the safety of single-stage bilateral excision of the internal jugular vein, as an adjunct to total thyroidectomy, in the surgical treatment of thyroid carcinoma.

Adult↗

Zinc, copper, manganese, and selenium metabolism in thyroid disease.

This study was designed to evaluate trace metal metabolism in adults with thyroid diseases. Erythrocyte zinc values were significantly lower than normal in hyperthyroidism and higher in hypothyroidism. A significantly higher than normal urinary excretion of zinc was observed in hyperthyroidism. The mean concentrations of plasma and erythrocyte copper were significantly above normal in hyperthyroidism. Plasma selenium levels were significantly lower than normal in hyperthyroidism. No statistically significant difference was found in plasma zinc, erythrocyte manganese, or urine copper values between patients with thyroid diseases and healthy controls. The erythrocyte manganese content correlated well with thyroxine and triiodothyronine levels. Plasma prealbumin and retinol-binding protein correlated well with the erythrocyte zinc content but not with plasma zinc levels. There was no correlation between erythrocyte superoxide dismutase activity and erythrocyte copper or zinc concentrations. The results of this study suggest that the metabolism of zinc, copper, manganese, and selenium is abnormal in thyroid diseases.

Adolescent↗

Low incidence of gross leukemia virus-induced lymphomas in spontaneously hypertensive rats with thymic dysfunction.

We compared the incidence of lymphomas induced by Gross leukemia virus (GLV) between spontaneously hypertensive rats (SHR) with a congenital T-cell depression related to thymic dysfunction and normal Wistar rats, the original strain of SHR. Of 20 SHR given neonatal injections of GLV, only 3 (15%) died with thymic lymphomas about 100 days after the virus infection. In contrast, 27 of 28 Wistar rats (96%) developed lymphomas of mostly thymic origin. The 3 lymphomas derived from the SHR bore only a Thy 1.1 antigen, whereas most of the lymphomas derived from Wistar rats carried not only a Thy 1.1 antigen but also a guinea pig red blood cell rosette receptor and a T (W3/13) antigen. Grafts of 1-week-old male Wistar thymus into the neonatal female SHR promoted a differentiation of thymocytes and markedly increased the incidence of the lymphomas which were positive for a guinea pig red blood cell rosette receptor and a T-antigen; grafts of 1-week-old SHR thymus, however, failed to do this. These results suggest that the low incidence of GLV-induced lymphomas in SHR may correlate closely with the absence or decreased numbers of the rosette-forming thymocytes which are presumably the target cells for GLV.

AKR murine leukemia virus↗

Salivary gland tumors in atomic bomb survivors, hiroshima, japan. II. Pathologic study and supplementary epidemiologic observations.

A pathological investigation was undertaken in Hiroshima on cases seen between 1945 and 1971 to determine the relationship between salivary gland tumors and exposure to atomic (A) bomb radiation. Of the 208 cases of histologically confirmed salivary gland tumors, 62 were A-bomb survivors and 146 were nonexposed. The relative risk based on the rate in the nonexposed for malignant tumors of salivary glands among the exposed in Hiroshima Prefecture was 11.0, while that of the submaxillary gland was 13.8 and that of the parotid gland was 9.8. They were all highly significant by X2 test (P less than 0.001). The latent period of malignant salivary gland tumors was shorter in the exposed than in the nonexposed. Four cases of benign salivary gland tumor, all being benign mixed tumors of the parotid gland, were observed in children whose parents had been exposed. The incidence of mixed tumors of the salivary gland among the exposed in Hiroshima City was 2.0 times higher than that among the nonexposed and showed a tendency to increase with proximity to the hypocenter (P less than 0.01).

Adenoma, Pleomorphic↗

Screening of various immunopotentiators in spontaneously hypertensive rats with T-cell depression.

A strain of SHR which develops hypertension spontaneously is marked by a selective depression of T-cell functions associated with an early appearance of natural thymocytotoxic autoantibody and a deficiency of thymic hormone. Present results demonstrate that various immunopotentiators (IPs) such as thymostimulin (TS), PS-K, SPG, neurotropin (NSP), and K-247 partially or almost completely reversed the T-cell depression in these SHR as detected by a rosette forming test, plaque-forming assay and blastogenesic response to PHA and Con A. In contrast, these IPs had no effect on the immune responsiveness of WKA rats with normal T-cell functions. Among the IPs, NSP, which had an almost complete restorative effect on the T-cell functions of SHR, induced significant transplantation resistance to the syngeneic tumor challenge. A new synthetic product K-247 also induced a significant suppression of lethal tumor growth in SHR, though its restorative effect on T-cell functions was weak. The fact that K-247 had a suppressive effect on tumor cell growth in vitro indicates that biochemical modifications rather than immunological ones may be involved. However, none of the IPs induced antitumor resistance in normal WKA rats. These results suggest that this strain of SHR provides a useful animal model for evaluation of various IPs.

4-Aminobenzoic Acid↗

Establishment and characterization of a differentiating myeloid cell line obtained from a rat myelomonocytic leukemia.

A long-term suspension culture line (c-WRT-7) was successfully established from a transplantable myelomonocytic leukemia induced by a neonatal injection of Rauscher leukemia virus in a WKA/Hok rat. A c-WRT-7 cell line was capable of being transplanted into syngeneic rats, and when transplanted, increased numbers of macrophage-like cells were observed in the peripheral blood of rats after i.v. injection. In in vitro culture, about 10% of the c-WRT-7 cells naturally differentiated into macrophage-like cells, which adhered to the bottom of a culture flask, and also possessed phagocytic activity. By means of cytological examination, about 30% of the c-WRT-7 cells were observed to be monoblastic with alpha-naphthyl butyrate esterase activity. The nature of these c-WRT-7 cells as a myelomonocytic leukemia line was constant during in vitro passages of more than 30 generations. In vitro treatment of c-WRT-7 cells with lipopolysaccharide, 12-O-tetradecanoylphorbol-13-acetate, or retinoic acid increased the numbers of differentiated cells with phagocytic activity to 80%. Treatment of the c-WRT-7 cells with the inducers also induced 15 to 20% of the cells to differentiate into metamyelocytes and segmented neutrophils. The Fc receptor and the complement receptor both became detectable on the surface of c-WRT-7 cells after treatment with lipopolysaccharide, 12-O-tetradecanoylphorbol-13-acetate, or retinoic acid. However, rosette-forming activity of sheep erythrocytes pretreated with neuraminidase which has been known as a marker of normal rat macrophages was not induced in c-WRT-7 cells. This shows that differentiated leukemic cells are not exactly identical with normal macrophages.

Animals↗

Immunologic suppression of carcinogenesis in spontaneously hypertensive rats (SHR) with T cell depression.

A strain of spontaneously hypertensive rats (SHR) showed a selective depression of T cell functions brought about by aging. Conversely, this strain had a high NK cell activity as compared to other normal rat strains. This SHR strain was found to be much more sensitive to the carcinogenic activity of low doses of MCA than were WKA rats with normal T cell functions. Allogeneic thymus grafts almost completely restored the T cell functions of SHR, whereas injection of an immunopotentiator, NSP, enhanced NK cell activity and also caused a partial recovering of T cell functions. When immunologic restoration was achieved, generation of killer T cells to syngeneic SMT-5 tumor cells was induced and the cytotoxic activity of NK cells to K-562 cells was also enhanced. But the cytotoxic activity to the SMT-5 cells of NK cells and macrophages from the treated or untreated SHR was not detected. Allogeneic thymus grafts induced a significant transplantation resistance against a syngeneic SMT-5 tumor and injection of NSP enhanced only the survival days of the rats. Allogeneic thymus grafts also significantly suppressed the incidence of tumors induced by MCA, whereas the injection of NSP was not effective in the prevention of tumor development but was effective in prolongation of latency periods. These results support the hypothesis that immune surveillance mediated by T cells is an important mechanism for the control of tumor development.

Animals↗