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Biomedical subjects

E Kubo

Publications and source records attributed to E Kubo.

At least 19 recordsLinked to original sources

Novel TCR gene rearrangements and expression in radiation-induced thymic lymphomas.

Using the intrathymic (i.t.) injection assay with a B10.Thy 1 congenic donor-host combination, we previously demonstrated that the pre-neoplastic cells (thymic prelymphoma cells) exist in immature T cell subpopulations; mainly in CD4-CD8- double negative (DN) and CD4-CD8+ single positive (SP) thymocytes and to some extent in CD4+CD8+ double positive (DP) thymocytes. Most thymic lymphomas that developed from these prelymphoma cells showed concomitant TCR alpha, beta and gamma gene rearrangements and expression. In this lymphomas, two lymphomas also showed TCR delta gene rearrangements. This represents the intermediate stages of TCR gene rearrangement. Every lymphoma, however, expressed CD3-associated alpha beta TCR on the cell surface, but not gamma delta TCR. Novel rearrangements of V gamma 4 and J gamma 4-C gamma 4 segments with non-gamma elements were found respectively in a concerted and symmetrical fashion. Recombinase-mediated inter-chromosomal exchanges characteristic of thymic lymphomas may function in radiation-induced lymphomagenesis.

Animals

Characterization of thymic prelymphoma cells that develop during radiation-induced lymphomagenesis in B10 mice.

An intrathymic (i.t.) injection assay on B10.Thy-1 congenic mice was used to demonstrate that thymic prelymphoma cells developed first within mouse thymus 4 to 8 days after split-dose irradiation and were present in more than 63% of the test donor mice thymuses examined 21 and 31 days after irradiation. For the characterization of these thymic prelymphoma cells, thymocytes from B10.Thy-1.1 mice sampled 1 mo after irradiation were stained with J11d mAb and mAb against TL-2 (thymus-leukemia) antigen which is not expressed on normal thymocytes of the B10.Thy 1.2 and B10.Thy 1.1 strains but does appear on thymocytes of split-dose irradiated mice. These cells were sorted into subpopulations, samples of which were injected into recipient thymuses to determine which subpopulations contained thymic prelymphoma cells. Results showed that the prelymphoma cells were located in the J11d+TL-2+ cells. These prelymphoma cells were further characterized phenotypically as to their expression of the CD4 and CD8 antigens, which demonstrated that the thymic prelymphoma cells were present in the CD4-CD8- and CD4-CD8+ thymocyte subpopulations mainly and in the CD4+CD8+ subpopulation. The experiments on i.t. injection of a graded quantity of TL-2+ thymocytes from individual mice suggest that not all TL-2+ cells undergo neoplastic initiation and that prelymphoma cells may develop infrequently from one or more TL-2+ cells by genetic or epigenetic changes.

Animals

Bone marrow-thymus interactions during thymic lymphomagenesis induced by fractionated radiation exposure in B10 mice: analysis using bone marrow transplantation between Thy 1 congenic mice.

Bone marrow transplantation (BMT) experiments were conducted using B10.Thy 1 congenic mice to explore the nature of bone marrow-thymus interactions during thymic lymphomagenesis induced by fractionated whole-body X-irradiation (FX). BMT from normal Thy 1 congenic donors into FX-treated recipients one day after FX-treatment resulted in the suppression of tumor development; the suppression being exponentially proportional to the increasing number of bone marrow cells injected. The suppression of tumor development by BMT was shown to be due to prevention of the appearance of prelymphoma cells. BMT from FX-treated donors, which are deficient in pre T cells, into lethally (9 Gy) irradiated Thy 1 congenic recipients resulted in the development of high incidence of thymic lymphomas most of which (approximately 76%) were host-derived, whereas no lymphomas were recovered from the recipients of normal bone marrow. These results suggest that intrathymic T cell precursors which initially repopulate the depleted thymus are prone to undergo preneoplastic changes in the absence of recruitment of more primitive T cell precursors (pre T cells) from the bone marrow but they undergo normal differentiation when large number of pre T cells are available. It was concluded that primary cause of the FX-induced thymic lymphomagenesis was a shortage in supply of pre T cells from the bone marrow to the depleted thymus, which caused differentiation arrest of the progeny of regenerating intrathymic T cell precursors, followed by development of prelymphoma cells that eventually evolve into autonomous lymphoma cells within the thymus.

Animals

Phenotypic characterization of thymic prelymphoma cells of B10 mice treated with split-dose irradiation.

Using an intrathymic injection assay on B10 Thy-1 congenic mice, it was demonstrated that thymic prelymphoma cells first developed within the thymuses from 4 to 8 days after split-dose irradiation and were detected in more than 63% of the test donor thymuses when examined at 21 and 31 days after irradiation. Moreover, some mice (25%) at 2 mo after split-dose irradiation had already developed thymic lymphomas in their thymuses. To characterize these thymic prelymphoma cells, the thymocytes from B10 Thy-1.1 mice 1 mo after irradiation were stained with anti-CD4 and anti-CD8 mAb and were sorted into four subpopulations. These fractionated cells were injected into the recipient thymuses to examine which subpopulation contained thymic prelymphoma cells. The results indicated that thymic prelymphoma cells existed mainly in CD4- CD8- and CD4- CD8+ thymocyte subpopulations and also in CD4+ CD8+ subpopulation. T cell lymphomas derived from CD4- CD8- prelymphoma cells had mainly CD4- CD8- or CD4- CD8+ phenotypes. T cell lymphomas developed from CD4- CD8+ prelymphoma cells mainly expressed CD4- CD8+ or CD4+ CD8+ phenotype. T cell lymphomas originating from CD4+ CD8+ prelymphoma cells were mainly CD4+ CD8+ but some CD4- CD8+ or CD4+ CD8- cells were also present. These thymic prelymphoma cells were further characterized phenotypically in relation to their expression of the marker defined by the mAb against J11d marker and TL-2 (thymus-leukemia) Ag, which is not expressed on normal thymocytes of B10.Thy-1.2 or B10.Thy-1.1 strain, but appears on the thymocytes of lymphomagenic irradiated mice. The results indicated that the prelymphoma cells existed in J11d+, TL-2+ cells.

Animals

New modified method for the surgical treatment of syndactyly.

We have been using Marumo's method for the surgical treatment of syndactyly. However, this method presents difficulties with incision designs, which we solved by devising a modified method. This method uses an angulated rectangular dorsal flap and a triangular miniflap made at the end of the dorsal flap. By rotating this miniflap proximally, the skin defect produced at the dorsal base of the digit after removal of the angulated dorsal rectangular flap becomes triangular. This triangular skin defect can be adequately covered by the triangular flap produced at the ventral side. In the article we describe this new operative method in detail and present cases to which the method has been applied.

Fingers

[A case of emergency replacement of SAM disk valve prosthesis for disk detachment].

A 47-year-old patient had undergone the mitral valve replacement using a SAM disk prosthesis in 1977. 15 years and 10 months after the first operation, she successfully underwent emergency replacement with a St. Jude Medical valve prosthesis because of detachment of the disk of the SAM prosthesis and now she is doing well.

Emergencies

Immediate and long-term effects of radiation on the immune system of specific-pathogen-free mice.

Studies on the immediate and long-term effects of radiation on the immune system of specific-pathogen-free mice are summarized in this paper. There was a striking difference in the radiation response of lymphocyte subsets; B cells consist of a fairly radiosensitive homogeneous population, whereas T cells consist of a large percentage (greater than 90 per cent) of radiosensitive and a small percentage (less than 10 per cent) of extremely radioresistant subpopulations. Ly 1+ and Ly 2+ lymphocytes appear equally radiosensitive, although the percentage of radioresistant cells was slightly larger for the former (approximately 5.5 per cent) than the latter (approximately 2.5 per cent). There was a significant strain difference in the radiosensitivity of immune-response potential in mice; immunocompetent cells of C3H mice were more radioresistant than those of BALB/c, C57BL/6, and B10.BR mice. Studies on the long-term effect of radiation on immune system in mice indicated no evidence for accelerated ageing of the immunologic functions when radiation exposure was given to young adults. Preliminary results on the enhancing effect of low dose radiation on cytotoxic T cell response in vitro are also discussed.

Animals

Development of prelymphoma cells committed to thymic lymphomas during radiation-induced thymic lymphomagenesis in B10 mice.

Intrathymic (i.t.) as well as i.p. injection of thymus cells from B10.Thy-1.1 mice manifesting overt thymic lymphomas, 4 months after split-dose irradiation, into B10.Thy-1.2 recipient mice resulted in the development of donor-type T-cell lymphomas, indicating that they contained "autonomous" lymphoma cells. In contrast, injection of thymus cells from apparently nonleukemic mice 1 month after split-dose irradiation resulted in the development of donor-type tumors only when they were injected i.t., suggesting that thymus cells from these mice contained "preneoplastic" cells that will eventually develop into thymic lymphomas under the influence of thymic microenvironment. These "thymus-dependent" preneoplastic cells were termed "thymic prelymphoma cells." With the use of i.t. injection assay, it was shown that these thymic prelymphoma cells were detected in 26.1% (6 of 23) of the test donor thymuses when examined at 14 days and in more than 63% (15 of 24 and 14 of 22) when examined at 21 and 31 days after irradiation. To examine the possibility that thymic prelymphoma cells might appear first in the bone marrow before they become detectable within the thymuses of the split-dose-irradiated mice, bone marrow cells from B10.Thy-1.1 donors recovered at 8, 14, 21, and 33 days after split-dose irradiation were also injected i.t. into B10.Thy-1.2-recipient mice. The results indicated that none of these recipients developed donor-type T-cell lymphomas, suggesting that bone marrow is not the first site of the appearance of thymic prelymphoma cells.

Animals

Cellular events during radiation-induced thymic leukemogenesis in mice: abnormal T cell differentiation in the thymus and defect of thymocyte precursors in the bone marrow after split-dose irradiation.

Cellular events during the development of thymic lymphomas in young B10.BR mice given leukemogenic split-dose irradiation were studied by examining the differentiation of functional T lymphocyte precursors in the regenerating thymus. It was found that leukemogenic radiation treatment resulted in a sustained depression of the level of thymic cytotoxic T lymphocyte precursors (CTLp) and of mixed lymphocyte reactivity of thymus cells when assessed between 1 and 4 mo after irradiation, in spite of the fact that the total number of thymocytes was restored to the normal level within 2 mo and continued to increase thereafter. In vitro mixing studies of normal thymocytes with thymus cells from split-dose irradiated mice provided no evidence for active suppression as a mechanism for this depressed activity. The ability of bone marrow cells from split-dose irradiated mice to regenerate the thymus and to differentiate into functional CTLp was examined by use of supralethally irradiated Thy-1 congenic recipients. Reconstitution of supralethally irradiated B10.BR Thy-1.2 mice with normal bone marrow from B10.BR Thy-1.1 mice resulted in the complete repopulation of host-thymus with donor-derived cells when assessed at 4 wk after reconstitution. Lymphocytes from the regenerating thymus of these animals were shown to contain high levels of CTLp which were donor-derived. On the other hand, when the recipient mice were reconstituted with bone marrow cells from donor mice which had been split-dose irradiated 1 mo earlier, regeneration of the recipient thymus was severely depressed when assessed at 4 wk to 3 mo after reconstitution. Although variable but small numbers of donor-derived Thy-1+ cells were detected, CTL activity for alloantigen could not be induced in these donor-derived cells. The results suggest that T cell precursors derived from split-dose irradiated donor mice were unable to undergo active proliferation and differentiation into functional CTLp. The significance of these findings on radiation-induced thymic leukemogenesis is discussed.

Animals

Strain difference in the radiosensitivity of immunocompetent cells and its influence on the residual host-vs-graft reaction in lethally irradiated mice grafted with semiallogeneic bone marrow.

A striking difference in radiosensitivity was noted between C3H/He (H-2k) and C57BL/6J (H-2b) strain mice when assessed by primary anti-SRBC PFC response of intact animals and primary cell-mediated lympholysis (CML) response of spleen cells to allogeneic cells in vitro, the C3H strain being more radioresistant. On the other hand, when C3H and B6 mice were exposed to 6.62 to 10.40 grays (Gy) of x-rays and then were transplanted with 2 X 10(6) bone marrow cells from B6C3F1 (H-2b/k) donor mice within 3 hr or at 24 hr after radiation exposure, the early mortality caused by residual host-vs-graft (HVG) reaction was much higher when C3H mice were used as recipients. Furthermore, the proportion of surviving animals manifesting host-type lymphohemopoiesis, i.e., host-type revertants, was much higher in B6C3F1 to C3H than in B6C3F1 to B6 combination. Spleen cells from such host-type revertants manifested strong anti-donor reactivity when assessed by mixed lymphocyte reaction (MLR) and/or CML in vitro. Increase of radiation doses to the recipients to 10.40 Gy resulted in 100% survival and 100% donor-type lymphohemopoiesis in both groups of chimeras. These results indicate strongly that a genetic difference in radiosensitivity of immune system of the recipients can greatly influence the magnitude of residual HVG reactions observed in hybrid to parental strain bone marrow transplantation in mice.

Animals

H-2 restriction specificity of T cells from H-2 incompatible radiation bone marrow chimeras: further evidence for the absence of crucial influence of the host/thymus environment on the generation of H-2 restricted TNP-specific T lymphocyte precursors.

Experiments were conducted to answer the questions related to (a) the role played by the antigen-presenting cells (APCs) present within the thymus and (b) the effect of radiation dose to the recipients on the H-2 restriction profile of TNP-specific cytotoxic T lymphocyte precursors (CTLP) recovered from spleens and/or thymuses of H-2 incompatible radiation bone marrow chimeras (BMC). The H-2 restriction profile of intrathymically differentiating TNP-specific CTLPs was also analyzed in order to test an argument that donor-H-2 restricted CTLP detected in spleens of H-2 incompatible BMC were due to the extrathymically differentiated T cells under the influence of donor-derived lymphoreticular cells. The results indicated the following: (i) splenic T cells from B10(H-2b) leads to (B10(H-2b) leads to B10.BR(H-2k)) chimeras, which were constructed by irradiating primary B10 leads to B10.BR chimeras with 1100 R and reconstituting them with donor-type (B10) bone marrow cells as long as 8 months after their construction, manifested restriction specificities for both donor- and host-type H-2, (ii) splenic T cells from two types of (B10 X B10.BR)F1 leads to B10 chimeras which were reconstituted after exposure of the recipients with either 900 or 1100 R with donor-type bone marrow cells generated both donor- and host-H-2 restricted TNP-specific cytotoxic T cells, and (iii) the TNP-specific CTLPs present in the regenerating thymuses of B10.BR leads to B10 and (B10 X B10.BR)F1 leads to B10 chimeras 4 weeks after their construction were also shown to manifest both donor- and host-H-2 restriction specificities. The significance of these findings on the H-2 restriction profile of CTLP generated in BMCs is discussed.

Animals

Treponema pallidum specific IgM haemagglutination test for serodiagnosis of syphilis.

The Treponema pallidum specific IgM haemagglutination (TP-IgM-HA) test uses erythrocytes sensitised with antiserum to human IgM to separate IgM from IgG in serum. Specific antitreponemal IgM captured in this way is detected by adding a second reagent comprising erythrocytes sensitised with T pallidum antigen. Eighty two serum samples from 82 patients with untreated syphilis, 521 samples from 73 patients with treated syphilis, and 1872 samples from people who did not have syphilis were examined by the 19S(IgM)-TPHA (T pallidum haemagglutination), IgM-FTA-ABS (fluorescent treponemal antibody absorbed), TP-IgM-ELISA (enzyme linked immunosorbent assay), and TP-IgM-HA tests for the presence of 19S(IgM) antibodies specific to treponemes. The sensitivity of the TP-IgM-HA test was 97.6% and the specificity was 99.7%. We also traced IgM specific to treponemes in untreated patients with primary syphilis by four different tests. The TP-IgM-HA test results clearly reflected the effect of the treatment.

Antibodies, Bacterial

Reconfirmation of indirect induction of radiogenic lymphomas using thymectomized, irradiated B10 mice grafted with neonatal thymuses from Thy 1 congenic donors.

An experiment was conducted to reexamine earlier observations that lymphomas could develop from lymphocytes present in nonirradiated thymuses grafted into thymectomized, fractionally (170 R, 4 doses) irradiated mice by using B10. Thy 1 congenic donor-host combinations. The results indicated that: (a) 37 of 91 thymectomized, fractionally irradiated B10. Thy 1.2 mice which were grafted s.c. with 7-day-old thymuses from B10. Thy 1.1 donor mice had developed frank lymphomas between 90 and 270 days after thymus grafting; (b) 28 of 37 lymphomas developed in this group were typed individually with respect to Thy 1 alloantigens by the cytotoxicity assay using monoclonal anti-Thy 1.1 (T-11-D7) and anti-Thy 1.2 (F7D5) antibodies plus complement. It was shown that 21 thymic lymphomas (75%) had originated from lymphocytes of the nonirradiated thymus grafts and 5 tumors (17.9%) from cells of the irradiated hosts; 2 thymic lymphomas (7.1%) manifested no Thy 1 antigens; (c) lymphoma cells originated from both nonirradiated thymus grafts and irradiated hosts possessed chromosome abnormalities, which were mainly numerical changes of some chromosomes or polyploidizations.

Animals

Induction of pigmentation by continuous X-irradiation of amelanotic tumors of B16-XI mouse melanoma and induced change in chromosomes of amelanotic cells.

Non-pigmented tumor cells of B16-XI mouse melanoma were found to contain a diploid number of chromosomes similarly to those of melanotic tumors and the parental cells in tissue culture. A major difference between pigmented and non-pigmented cells was in the number of biarmed chromosomes per cell. There was no difference in growth rate between non-pigmented and pigmented tumors, but growth usually begins about 2 days earlier in the former. Pigmentation lost in the course of serial transplantation was restored by irradiating the non-pigmented tumor continuously with 2,500-3,000 rads/passage of X-rays during six transfer generations. In the course of repeated irradiations, the chromosomes changed structurally and numerically as the pigmentation of the tumor was gradually restored. The observations of tumor growth and chromosomal changes are discussed in relation to the pigmentation of B16-XI melanoma cells.

Animals