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Biomedical subjects

N Takeichi

Publications and source records attributed to N Takeichi.

At least 181 records · Page 10Linked to original sources

[Two cases of large functioning parathyroid adenoma in atomic bomb survivors].

In a study by the Radiation Effects Research Foundation, Hiroshima and Nagasaki, of parathyroid tumors in autopsy cases, 18 cases of parathyroid adenoma were detected among 6, 102 cases that were autopsied between 1961-77. Two of these were giant adenomas 5 cm in diameter, complicated with hyperthyroidism. Both were atomic bomb survivors of Hiroshima. One was exposed to 55 rad at the age of 51 and died at age 71. The other was exposed to 28 rad at age 44 and died at age 71. These two cases are reported with a review of the literature on parathyroid tumors that developed following irradiation of the head and neck.

Adenoma↗

Chromosome and cell surface marker studies in 1-propyl-1-nitrosourea-induced thymic lymphomas of the rat.

Immunological cell surface markers were studied in seven transplantable 1-propyl-1-nitrosourea-induced thymic lymphoma lines in F344 rats by reactivity to anti-Thy-1.1, anti-rat Ig (anti-Ig), and anti-rat T-cell (anti-T) sera, and by the capacity to form rosettes with guinea pig red blood cells. All the tumor lines were estimated to be sensitive to anti-Thy-1.1 but insensitive to anti-Ig serum in the presence of complement. The differences in reactivity to anti-T serum and rosette-forming capacity (RFC) allowed classification of the lines into three types. In type I, three lines were highly sensitive to anti-T serum but low in RFC, indicating that these lymphomas probably originated from relatively mature intrathymic T cells. In type II, two lines were moderately sensitive to anti-T serum and relatively high in RFC, indicating that these lymphomas derived from intrathymic T cells. In type III lymphomas, the remaining two lines were not only insensitive to anti-T serum but also low in RFC, suggesting that these lymphomas might have arisen from immature precursors of T and/or B cells. The chromosome study revealed that type I lymphomas were diploid, with slight numerical and structural variations. Type II lymphomas were pseudodiploid or hypotetraploid, with considerable variation in the number and morphology of chromosomes. Type III lymphomas had a diploid or hyperdiploid constitution, with a moderate degree of karyotypic variation. Neither consistent nor common karyotypic alterations among the seven lines were found, although the karyotypic instability seemed to be related to the immunological types of the lymphoma lines, possibly reflecting the differentiation process of the target cells involved in the malignant transformation.

Animals↗

Restoration of T cell depression and suppression of blood pressure in spontaneously hypertensive rats (SHR) by thymus grafts or thymus extracts.

Spontaneously hypertensive rats (SHR) that develop hypertension and arterial lesions resembling human periarteritis nodosa were found to possess a selective depression of T cell functions with an appearance of natural thymocytotoxic autoantibody (NTA). The relationship between T cell depression and hypertension in these animals was investigated. The immune responsiveness of T cell-depressed SHR was completely recovered by histocompatible thymus grafts and was partially restored by histoincompatible allogeneic or xenogeneic thymus grafts or by injection of thymus extracts. Transplantation of compatible thymus tissues into neonatal SHR produced long-lasting recovery of immune functions. When complete immunologic restoration was achieved, significant suppression of high blood pressure was obtained. The SHR that showed high blood pressure were always accompanied with high NTA titers and arterial lesions. Thymus grafts or thymus extracts significantly decreased the titers of NTA. The development and dissemination of arterial lesions, which may cause increased blood flow resistance, were completely prevented by compatible thymus grafts into neonatal SHR. These results suggest that thymus grafts and thymus extracts may suppress the development of hypertension by preventing or curing the periarteritis nodosa in SHR.

Aging↗

[Immunological analysis of immunopotentiators in spontaneously hypertensive rats with T-cell depression (author's transl)].

A strain of spontaneously hypertensive rats (SHR) had a selective depression of T-cell functions associated with an early appearance of natural thymocytotoxic autoantibody and a deficiency of thymic hormone. In this paper, the ability of immunopotentiators (IPs) to restore immune functions and to induce antitumor resistance in the T-cell depressed SHR is investigated. In addition, the effect of IPs on activities of natural killer (NK) cells and macrophages is also studied. The results indicate that administration of SPG or Lysozyme enhanced T-cell functions as detected by the rosette formation test and blastogenic responses to PHA. None of the IPs used promoted NK cell activity but Lysozyme and PS-K rather suppressed. In contrast, all IPs used had a effect on activation of macrophages and especially PS-K showed strong activating effect. Following survival and tumor rejection in SHR transplanted with a syngeneic tumor after treatment with the IPs, treatment with SPG produced significant prolongation of survival days but the remaining two IPs had no effect. We propose that the SHR is a suitable animal for quantitative evaluation of the IPs in inducing T-cell mediated immunity an antitumor immune responses.

Adjuvants, Immunologic↗

Characterization of immunological depression in spontaneously hypertensive rats.

Immunocompetent cell functions were evaluated in spontaneously hypertensive rats (SHR). Hematological studies revealed decreased absolute numbers of lymphocytes and increases number of polynucleic cells in the peripheral blood of SHR. The SHR had a reduced number of immature T lymphocytes in their thymuses in comparison with an original strain of Wistar rats, as detected by the rosette formation test with guinea pig erythrocytes. The antibody response to sheep red blood cells (SRBC) of the 3-month-old SHR was profoundly depressed and was about one-teeth that of the Wistar rats. Cell cooperation experiments suggest that the T lymphocytes of the SHR were selectively impaired in antibody responses to SRBC in cooperation with B lymphocytes. B lymphocytes from the bone marrow of the SHR were not affected and produced normal numbers of plaque-forming units. Cyclophosphamide treatment, which selectively depletes suppressor T lymphocytes, did not enhance the delayed-type hypersensitivity response to SRBC in SHR. This may rule out the possibility of the involvement of the suppressor mechanism in the T cell depression of the SHR.

Animals↗

Relationship between the radioisotopic footpad assay and other immunological assays in tumor bearing rats.

KMT-17, a fibrosarcoma induced by 3-methylcholanthrene in a WKA rat, is a sensitive tumor to various kinds of immunological assays and is a suitable model tumor for the study of the immune status in tumor bearing hosts. The antitumor immune response of KMT-17 bearing rats was studied by a radioisotopic footpad assay (FPA) in comparison with other in vivo and in vitro assays. Delayed hypersensitivity to tumor antigens measured by the FPA was observed from the 8th day after transplantation of KMT-17 cells, reached a peak on the 12-15th day, and then declined in the late stage on the 17th day. The kinetics of the FPA correlated well with those of an in vivo Winn assay and of an in vitro lymphocyte cytotoxicity assay (51Cr-release assay). The appearance of an antitumor antibody detected by a complement dependent cytotoxicity test also correlated well with the kinetics of the FPA. A growth inhibition assay (GIA) for non-specific cell-mediated immunity also showed similar kinetics to that of the FPA. The delayed hypersensitivity footpad reaction to tumor cell extracts measured by this FPA was tumor-specific. These results suggest that the FPA is a simple and reliable in vivo assay for evaluating antitumor immunity in tumor bearing host.

Animals↗

Enhancement of antitumor transplantation resistance in rats by appropriately timed administration of busulfan.

Enhancement of specific transplantation resistance to a syngeneic tumor (KMT-17) was observed in WKA rats by treatment with the antileukemia drug busulfan (BU) (15 mg/kg) 5 days before and 5 days after immunization with X-irradiated KMT-17 tumor cells. Rats immunized with X-irradiated KMT-17 cells and then treated with BU showed specific transplantation resistance only against KMT-17 tumor. Carrageenan administration after BU treatment had no effect on enhancement by BU, which indicated that macrophages were not playing a major role in the observed enhancement. With the Winn assay, it was found that spleen cells from rats immunized with X-irradiated tumor cells followed by BU inhibited the growth of admixed tumor cells more strongly than did spleen cells from rats only immunized or only BU treated and that the tumor-neutralizing activity of spleen cells from rats treated by immunization followed by BU was abrogated by treatment with anti-T-serum and complement. It was suggested that the enhanced antitumor transplantation resistance caused by BU was due to enhanced T-cell immune responses to tumor cells. Enhancement of anti-tumor transplantation resistance by BU was significantly abrogated by adoptive transfer with thymus cells and was slightly abrogated with spleen cells from rats immunized with X-irradiated KMT-17 cells 1 day before tumor challenge but receiving no other treatment. Transfer of sera from the immunized rats had no effect on enhancement by BU. These results, taken together, suggest that the mechanism of the enhancement by BU involved a selective elimination of the immunosuppressor cells from the immunized hosts.

Animals↗

[Restoration of immune functions in T-cell depressed spontaneously hypertensive rats (SHR) by injection of neurotropin (author's transl)].

A strain of spontaneously hypertensive rats (SHR) showed a progressive decline in T-cell functions with aging. In order to restore the depressed immune functions, the effect of immunopotentiators such as Neurotropin, PS-K or thymus extract on immune responses of SHR was studied. The results presented here demonstrated that injection of Neurotropin completely restored the T-cell functions in SHR as detected by a rosette forming test, a plaque forming assay and blastogenesis. Administration of thymus extract also restored the immune functions except helper T-cell activity. However, administration of PS-K increased only numbers of rosetting cells in the thymus of SHR. Biological significance of Neurotropin as immunopotentiators was discussed.

Adjuvants, Immunologic↗

Effect of horse antibody to rat alpha-fetoprotein upon the growth of AH-66 in Donryu rats.

Studies were undertaken to evaluate whether the intraperitoneal administration of horse antibody to rat alpha-fetoprotein (HabRatAFP) would inhibit or prevent the growth of AH-66 tumor cells inoculated into Donryu male rats. In animals inoculated with tumor subcutaneously there was 100% tumor growth in uninjected control animals and the administration of HabRatAFP prevented tumor growth in 7/24 (29%) of the animals. When animals were inoculated with tumor intraperitoneally, the inhibition of tumor growth by HabRatAFP only occurred at tumor-cell doses of 50,000, 10,000, and 5,000. In these three groups, 15/35 (43%) of those animals treated with HabRatAFP did not develop tumor whereas 1/36 (3%) of the normal horse-serum treated animals did not develop tumor. The majority of those animals which were cured of their tumors by HabRatAFP treatment resisted tumor rechallenge. Studies were done to elucidate the mechanisms responsible for the anti-tumor effect of HabRatAFP, AH-66 tumor cells which were placed into millipore chambers, implanted intraperitoneally, were killed by the intraperitoneal administration of HabRatAFP. Studies were conducted to see if treatment with HabRatAFP to rat AFP might increase the immunogenicity of an inoculum of X-irradiated tumor cells. In one experiment, no animals which received only X-irradiated tumor cells resisted tumor rechallenge with 5 X 10(6) tumor cells whereas 6/11 (54.5%) of those animals which received X-irradiated tumor cells and treatment with HabRatAFP resisted tumor rechallenge.

Animals↗

Non-H-2-linked genetic control of resistance to BALB/c fibrosarcoma Meth-A.

The genetic control of hybrid resistance to BALB/c fibrosarcoma Meth-A was investigated. A Meth-A tumour grew slower in (BALB/c x C57BL/6)F1 and reciprocal hybrid mice than in syngeneic BALB/c mice and was also found to grow slower in females than in males. Significant F1 resistance was demonstrated after both subcutaneous and intraperitoneal injection of tumour cells. However, (BALB/c x DBA/2)F1 mice did not show any significant resistance to Meth-A. In H-2 linkage studies of [BALB/c x (BALB/c x C57BL/6)] backcross mice, no statistically significant differences in the resistance of H-2 heterozygotes and homozygotes to Meth-A were observed. These results indicated that F1 hybrid resistance to Meth-A was controlled by non-H-2-linked resistance factor(s). No linkage was observed between resistance to Meth-A and coat colour c- and b-loci.

Animals↗

Enhanced immunogenicity of xenogenized tumor cells in rats pretreated with cyclophosphamide.

Immunization with xenogenized tumor cells, tumor cells infected with murine leukemia viruses, produced strong antitumor immunity. In this study, the immunogenicity of xenogenized tumor cells was compared in cyclophosphamide-treated and non-treated rats. CY treatment 3 days before immunization with xenogenized tumor cells enhanced antitumor cell-mediated immunity and antibody responses. However, CY treatment after immunization had no effect. Transfer of thymus cells form normal rats before the tumor challenge abolished the CY-induced augmenting effect. From these results, it is suggested that the elimination of precursors of suppressor T-cells by CY treatment results in enhanced immunogenicity of xenogenized tumor cells.

Animals↗

Characterization of immunosuppressor cells in rats immunized with solubilized tumor-associated antigens prepared from a methylcholanthrene-induced fibrosarcoma.

Antiimmune responses in rats previously immunized with soluble tumor antigens prepared by sodium deoxycholate (DOC-STA) from chemically induced fibrosarcoma KMT-17 were measured by the Winn assay. Enhancement of tumor growth was demonstrated at a tumor:effector ratio of 1:500 with DOC-STA-immune spleen cells, although inhibition of tumor growth was demonstrated at a tumor:effector ratio of 1:100. The tumor-neutralizing ability of KMT-17-immune spleen cells was abrogated when DOC-STA-immune spleen cells were added to a mixture of KMT-17 cells and KMT-17-immune spleen cells. This suppressor activity of the spleen cells was diminished by the treatment with rabbit anti-rat T-cell serum and immune complement. The suppressor activity of DOC-STA-immune spleen cells was also shown in 51Cr release assay and was specific for the tumor line used. After fractionation of spleen cells from DOC-STA-immune rats by the Ficoll density gradient, the cells in the light layer showed an enhancing effect on tumor growth detected by the Winn assay, whereas the cells in the heavier region of the gradient had an inhibiting effect.

Animals↗

Immunological depression in spontaneously hypertensive rats.

Cell-mediated immunity was investigated in spontaneously hypertensive rats (SHR). The thymuses of young SHR rats before developing hypertension had reduced numbers of immature T lymphocytes which were detected by the rosette formation test with guinea-pig erythrocytes in the presence of foetal bovine serum, whereas the thymuses of eight other rat strains tested contained about 60% of rosetting cells. The number of rosetting cells decreased progressively with age. The blastogenic responses to PHA and Con A of the SHR rats' lymphocytes was depressed to less than one-fifth when compared to those of othe rat strains including W/7k rats, the original colony of the SHR rats. Eight-month-old SHR rats showed fewer mitogenic responses than those of 2-month-old SHR rats. Other cell-mediated immune responses, including delayed hypersensitivity, allograft rejections, and a co-operation of T and B lymphocytes to produce humoral antibody formation were depressed significantly when compared to those of other rat strains. Possible mechanisms of immunological depression in the SHR rats in relation to the devleopment of hypertension are discussed.

Aging↗

Development of runting syndrome in Friend and Gross virus-induced doubly tolerant rats.

Neonatal injections of Friend virus (FV) or Gross virus (GV) into rats produced immunological tolerance to the virus-induced tumors. The inoculation of specific immune lymphoid cells into the FV-induced tolerant rats brought about the runting syndrome, whereas the GV-induced tolerance was completely abrogated by the same procedure. To investigate the mechanism of the runting syndrome, rats were made doubly tolerant by neonatal injections of a mixture of FV and GV. The adoptive transfer of lymphoid cells from rats immunized with the FV-induced lymphomas into the doubly tolerant rats produced the runting syndrome. On the other hand, adoptive transfer of lymphoid cells from rats immunized with GV lymphomas into the doubly tolerant rats did not produce the runting syndrome and broke down the GV-induced tolerance but not the FV-induced tolerance. By the use of a complement-dependent cytotoxicity test, FV-infected cells were homogeneously detected in thymus, spleen, and bone marrow of the doubly tolerant rats, whereas GV-infected cells were detected only in the thymus. Studies with a rosette formation test as a rat thymus marker showed that none of the FV lymphomas formed rosettes with guinea pig erythrocytes, whereas GV lymphomas formed rosettes. These results suggest that FV and GV have different target cells for infection and transformation and that the development of the runting syndrome is closely associated with infection of bone marrow and spleen cells with FV.

AKR murine leukemia virus↗