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T Sado

Publications and source records attributed to T Sado.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Assessment of prognostic factors in surgical treatment for the pulmonary metastasis of osteosarcoma based on results of 17 patients].

Seventeen cases with surgical treatment for pulmonary metastases of osteosarcomas have been experienced for past 20 years in our institute. Disease free intervals, tumor doubling time, the number of metastatic lesions, the size of metastatic lesions, pathological features on nuclear findings were assessed in relation to their prognosis. These parameters were concluded to have no significant relations to the survival outcomes after the surgery for pulmonary lesions except for the number of metastatic lesions less than 20 in total which is likely to be associated with long survivals, supporting previous reports on the resectability of pulmonary metastatic lesions as an only reliable prognostic indicator. It was also stressed from our experience that the meticulous follow-up after each surgery for both primary and metastatic lesions is absolutely necessary for the early detection of recurrent pulmonary lesions in order not to overlook curable cases with aggressive treatment.

Adolescent↗
PubMed1996

Distribution of Fv-4 resistant gene product in Friend leukemia virus-resistant Fv-4r mouse strain.

Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We demonstrated previously that the Fv-4 resistant (Fv-4r) gene product, Fv-4r env antigen, is released from Fv-4r-bearing BALB/c-Fv-4Wr (C4W) mouse-derived cells into serum in vivo and binds to cells expressing surface receptors for ecotropic MuLV, thereby protecting them from infection with Friend leukemia virus (FLV) by receptor interference. This unique resistance mechanism against retroviral infection might provide a possible therapeutic model system of human retroviral infection such as AIDS. To further investigate the Fv-4r gene action in vivo, we examined the distribution and character of Fv-4r env antigen in serum and systemic organs from C4W mice. The Fv-4r env antigen was immunohistochemically localized to the lympho-hematopoietic cells and exocrine glandular cells, such as those of the salivary gland and pancreas. Using immunoprecipitation followed by Western blotting, we determined two types of gp70-related Fv-4r env antigen in the serum of C4W mice, showing molecular weights of either 70-75 kDa and 80-85 kDa. When thymocytes from Fv-4 susceptible gene (Fv-4r)-bearing C3H mouse were mixed with C4W mouse serum, the 70-75k Da molecule of the C4W serum dominantly bound to C3H thymocytes and thus contributed to receptor interference function. Using immunoelectron microscopy, Fv-4r env antigen was mainly localized to the cell surface membrane of thymic lymphoid cells, while acinar cells of the salivary gland possessed Fv-4r env antigen in the endoplasmic reticulum (ER) as well as on the cell surface membrane. These data indicate that several glandular organs, as well as lymphohematopoietic organs of C4W mice, may contribute to the production of cell-free Fv-4r env antigen, resulting in protection of cells from infection with FLV by receptor interference.

Animals↗
PubMed1996

[Present international status and basic approach of lung and heart-lung transplantation].

Lung transplantation has been established as an optional treatment for variable irreversible diffuse lung diseases. To date, more than 5,000 patients have underwent lung transplantation, and nearly 1,000 procedures a year are performed recently. Although heart-lung transplantation has also been technically established, this procedure is confined to quite limited conditions due to the severe shortage of donors and many difficulties in operative procedure and the patient management. Preservation, post-transplantation edema, diagnosis of rejection, chronic rejection, shortage of donor organs, are principal problems in clinical lung transplantation, 24-hour preservation proved to be possible in several recent experimental studies, and the reperfusion injury has been revealed to be one of causes of post-transplantation edema. Establishment of methods for long-term pulmonary preservation and for the treatment of post-transplantation edema may be promising in the near future. Shortage of donor lung is one of major limiting factors. Research works on xenotransplantation and cadaver lung transplantation are on going, and these may help in solving this problem.

Heart-Lung Transplantation↗
PubMed1995

Cell-free transmission of Fv-4 resistance gene product controlling Friend leukemia virus-induced leukemogenesis: a unique mechanism for interference with viral infection.

Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We previously demonstrated that mixed radiation bone marrow chimeras containing Fv-4r-bearing BALB/c-Fv-4Wr (C4W) bone marrow and Fv-4r-bearing C3H/He (C3H) bone marrow grafted into C3H recipient mice (C4W+C3H-->C3H) were resistant to Friend leukemia virus (FLV)-induced leukemogenesis, even when they contained as high as 70% C3H-derived cells. This indicates that FLV-sensitive C3H-derived cells are rendered refractory to infection and/or transformation with FLV when they coexist in mice with Fv-4r-bearing cells. To investigate the mechanism of Fv-4 resistance to FLV-induced leukemogenesis, we first examined the expression of Fv-4r env antigen in the peripheral blood mononuclear cells (PBMC) of these chimeras. The Fv-4r env antigen was present not only on C4W-derived cells, but also on Fv-4r-bearing C3H-derived cells in C4W+C3H-->C3H mixed bone marrow chimeras. The Fv-4r env antigen that binds to the cells surface of C3H cells was found in sera from normal C4W mice, C4W-->C3H chimeras, and C4W+C3H-->C3H mixed chimeras. The serum Fv-4r env antigen binds to ecotropic MuLV receptors, shown by specific binding to transfectant mink cells expressing ecotropic MuLV receptor, but not to parental mink cells. To determine whether the binding of Fv-4r env antigen to the putative MuLV receptors would block FLV infection, C3H thymocytes or spleen cells that had been preincubated with C4W serum were mixed with FLV and the subsequent production of MuLV specific antigens was examined. C3H thymocytes or spleen cells treated with C4W serum became refractory to binding by FLV. These results provide evidence that the Fv-4r env antigen is released from C4W-derived cells in vivo and binds to cells expressing surface receptors for ecotropic MuLV, thereby protecting them from infection with FLV. The implication of these findings for gene therapy of retrovirus-induced disease such as acquired immune deficiency syndrome (AIDS) is discussed.

Animals↗
PubMed1995

The characterization of the monoclonal antibody Th-10a, specific for a nuclear protein appearing in the S phase of the cell cycle in normal thymocytes and its unregulated expression in lymphoma cell lines.

A monoclonal antibody (Th-10a) specific for the nuclear protein appearing in the S phase of the cell cycle in normal mouse thymocytes was derived by immunizing Wistar rats with a murine thymic lymphoma (TIGN), and its isotype was rat IgG2a and had kappa light chain. Immunohistochemical staining of frozen sections of B10.Thy1.1 newborn thymus and embryonic intestine revealed that this monoclonal antibody reacted strongly with the nuclear proteins of subcortical thymocytes and the basal layer of the mucosa, where many cells were dividing, but not with that of the thymic medullary area. To evaluate the expression of the nuclear proteins during the cell cycle in detail, the results of an immunofluorescence analysis of the thymocytes from hydroxyurea-treated B10 mice using Th-10a monoclonal antibody were compared with those of DNA synthesis of these cells with the use of the FITC-conjugated anti-BrdUrd monoclonal antibody. The results indicated that the nuclear protein detected by Th-10a monoclonal antibody was highly expressed in the S phase of normal thymocytes, while the cells in G1, G2 and M phases exhibited a low level of the expression. Moreover, the variations in expression of the nuclear proteins in the thymocytes at different times after hydroxyurea treatment were observed to correspond with the frequency of DNA synthesizing cells. In contrast, the high level and unregulated expression of the nuclear protein detected by Th-10a monoclonal antibody was observed throughout the cell cycle of the mouse lymphoma cell lines examined. Since Th-10a monoclonal antibody does not react with the nuclear proteins derived from human, hamster or rat proliferating cells, this antibody may recognize a murine specific epitope of the nuclear protein. To further characterize the nuclear proteins, we extracted them from normal thymocytes or thymic lymphomas, and analysed them by immunoblotting or immunoprecipitation followed by SDS-polyacrylamide gel electrophoresis. The nuclear protein(s) detected by Th-10a monoclonal antibody was mostly 95 kDa and also 83 kDa polypeptide. The results also indicated that the 95 kDa nuclear protein was phosphorylated in vivo.

Animals↗
PubMed1995

[Surgical treatment of metastatic lung tumor from colorectal cancer].

We have experienced thirty-one operations of metastatic lung tumors from colorectal cancer. Various factors affecting prognosis are studied based on 5-year survival in this report. Overall 5-year survival rate was 32%. Statistical significance was present in the relationship between the prognosis and both maximum diameter of lesions and the disease free intervals (DFI) after surgery for metastatic lesions. Though not significant, sex, stage of primary lesion, nodal involvement, surgical procedure, postoperative serum CEA were likely affecting factors on the prognosis. In contrast, there were no relationship between the prognosis and following factors: age, location of the metastatic lesion, DFI after the operation for primary lesion and chemotherapy. Although pulmonary metastasis is essentially an index of the advanced state of malignant diseases leading to poor prognosis, long-term survivors were encountered in our series of surgical treatments for pulmonary metastases from colorectal cancers. It was concluded to be important to make efforts to extend the indication for surgical treatment, since the appropriate selection of patients revealed to give excellent results from our experience of colorectal cancer. In order to improve the prognosis, early detection of pulmonary metastases is quite important, since the incidence of nodal involvement proved to be higher in lesions with larger diameter resulting in inferior survivals from the present study. In addition, low incidence of nodal involvement in small-sized lesion may support possible applicability of thoracoscopic surgery in the excision of metastatic tumors locating at peripheral lesion.

Adult↗
PubMed1995

An MHC-compatible allogeneic bone marrow donor with a distinct role of T cell subsets in graft-versus-leukemia effect and lethal graft-versus-host disease.

Our previous results in a murine model indicated that the GVL effect against radiation-induced leukemias could be induced in not only MHC-incompatible but also MHC-compatible allogeneic BMT, and that the intensity of the GVL effect induced in MHC-compatible allogeneic BMT varied among different leukemias and the donor/host strain combinations used. With the use of a radiation-induced T cell leukemia which followed the induction of the GVL effect in both MHC-compatible and -incompatible, allogeneic BMT, the role of T cell subsets in the development of the GVL effect and GVHD was studied. The results indicated that Lyt2+ T cells contaminating donor BM were consistently critical for the induction of the GVL effect in MHC-incompatible (B10) and -compatible (B10.BR and AKR) allogeneic BMT of leukemia-bearing C3H mice, but the depletion of L3T4+ T cells had no effect. In contrast, lethal GVHD induced by AKR donor lymph node cells was totally dependent on L3T4+ T cells, but the depletion of Lyt2+ T cells had no effect. On the other hand, both T cell subsets could cause lethal GVHD induced by MHC-incompatible (B10) and -compatible (B10.BR) allogeneic donors. The distinct roles of T cell subsets of AKR donors were confirmed by the preferential induction of the GVL effect with the AKR donor bone marrow mixed with lymph node cells which had been depleted of L3T4+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Experimental study of lung transplantation from non-heart-beating donor following brain death in canine model of left lung allotransplantation.

Thirty mongrel dogs were divided into 3 groups. Group I was a normal control group (n = 4) without transplantation procedure. Group II was a transplantation control group (n = 5) with left lung allotransplantation from heart-beating donor. Group III consisted of animals (n = 8) which received lung allografts from non-heart-beating donor following brain death. In Group III, brain death was brought about by intracranial hypertension with the inflation of balloon in the subdural space of donor. After 6 hours, the mechanical ventilation was discontinued followed by cardiac arrest. Left lung was excised twenty minutes after the cardiac arrest and was washed out with cold Ep4 solution for subsequent orthotopic allotransplantation. Right pulmonary arterial occlusion test (RPAO) were carried out under right thoracotomy to evaluate graft function immediately and 7 to 14 days after the surgery. PaO2, PAP and CO were measured before and 20 minutes after RPAO. All animals in Group II and 7 of 8 animals in Group III survived more than 7 days after surgery. No significant differences in the value of PaO2, mean PAP and TPVR with RPAO among three groups at each time of assessment, showing the possibility of lung transplantation from non-heart-beating donor followed by brain death.

Anesthesia↗
PubMed1994

Bone marrow transplantation from Fv-4-resistant donors rescues Friend leukemia virus-infected mice from leukemia: a model of bone marrow transplantation therapy against retroviral infection.

Bone marrow transplantation experiments were conducted in mice in order to develop an experimental bone marrow transplantation therapy model, with which to investigate possible means to cure retrovirus-infected hosts with bone marrow or stem cells from virus-resistant donors. In one experiment, lethally irradiated Friend leukemia virus (FLV)-sensitive C3H/He (C3H; Fv-2s, Fv-4s, Rfv-1s, Rfv-2s Rfv-3s) mice were transplanted with (i) bone marrow cells from FLV-resistant BALB/c-Fv-4Wr (C4W; Fv-2s, Fv-4r, Rfv-1s, Rfv-2s, Rfv-3s) mice (C4W --> C3H) or (ii) a mixture of bone marrow cells from C4W and C3H mice (C4W + C3H --> C3H). They were then inoculated with FLV 3-4 months later and leukemia development was examined. The results indicated that C4W --> C3H chimeras were completely resistant to FLV-induced leukemogenesis and that C4W + C3H --> C3H mixed chimeras that contained as low as 30% C4W-derived cells, or as high as 70% C3H-derived cells, did not develop leukemias. In another experiment, bone marrow cells from C57BL/6 (B6; Fv-2r, Fv-4s, Rfv-1r, Rfv-2r, Rfv-3r) or C4W donors were grated to FLV-sensitive DBA/2 mice (DBA; Fv-2s, Fv-4s, Rfv-1s, Rfv-2s, Rfv-3s) that had been infected with FLV 6 days earlier (DBA-FLV). The results indicated that most, if not all, FLV-infected DBA mice which received bone marrow transplantation from B6 donors developed B6-derived leukemias, although the survival time of these mice was dramatically prolonged as compared to that of untreated DBA-FLV mice. In contrast, bone marrow transplantation from Fv-4r-bearing C4W donors successfully rescued FLV-infected DBA mice from leukemic deaths. Thus, the bone marrow transplantation therapy against retroviral infection of hemopoietic cells was shown to be feasible, provided that donor cells carry a resistant allele that functions via receptor blockade as in the case of Fv-4r, but less effective when the roles of the resistant alleles partially interfered with the virus replication, leukemic transformation and/or cycling of target cells as suggested for Fv-2r gene action, or to resist virus infection by immunological means as are known for Rfv-1r, Rfv-2r and Rfv-3r genes which are also carried by B6-strain mice. Implication of these findings on the somatic gene therapy against retrovirus infection diseases in man are discussed.

Animals↗
PubMed1994

Graft-versus-leukemia effect in allogeneic bone marrow transplantation in mice against several radiation-induced leukemias.

The intensity of graft-versus-leukemia (GVL) effect was studied using several radiation-induced leukemia cell lines (designated 8027, 8313, 9107, 7929) in MHC-compatible and -incompatible allogeneic bone marrow transplantation (BMT) of leukemia-bearing C3H mice. The results indicated that BMT from MHC-incompatible allogeneic (B10, B10.D2) donors consistently improved the survival of the treated mice compared with that in syngeneic (C3H) donors. However, BMT from MHC-compatible allogeneic (B10.BR, CBA, AKR) donors failed to improve the survival of 8027-bearing recipients. On the other hand, a remarkable improvement in survival of 8313, 9107 or 7929-bearing recipients was observed in MHC-compatible allogeneic (B10.BR, AKR) BMT but there was only a marginal GVL effect in MHC-compatible BMT from CBA donors. There was no clear correlation between the intensity of GVL effect and the amount of class I MHC molecules expressed on leukemic cell lines. The activity of donor lymph node cells for the induction of lethal graft-versus-host disease (GVHD) correlated with the intensity of GVL effect induced by intact donor bone marrow. The results indicate that GVL effect against radiation-induced leukemias could be consistently induced in MHC-incompatible allogeneic BMT whereas the intensity of GVL effect induced in MHC-compatible allogeneic BMT varied among different leukemias and the donor-host strain combinations used.

Animals↗
PubMed1993

Nucleotide sequence of a mouse lamin A cDNA and its deduced amino acid sequence.

We have cloned and determined the nucleotide sequence of a mouse lamin A cDNA. The clone contained the C-terminal two-thirds of the lamin A coding sequence and a 3' untranslated sequence with a poly(A) stretch. As has been reported for human lamin A/C cDNAs, a large part of the 5' sequence of our mouse lamin A clone was essentially identical with a previously reported mouse lamin C cDNA sequence, and the deduced C-terminal amino acid sequence shared strong homology with the human lamin A sequence. A putative deduced amino acid sequence for mouse lamin A, which was derived from our sequence and the published lamin C sequence, was 665 amino acids long. The degree of overall homology to the human sequence was more than 95%, and relatively more variation was scattered in the C-terminal lamin A-specific region.

Amino Acid Sequence↗
PubMed1993

Multiple pre-neoplastic events and clonal selection of radiation induced mouse thymic lymphomas shown by TCR gene rearrangements.

After split-dose irradiation, pre-lymphoma cells develop from a tumor-specific surface antigen TL-2+ thymocyte subpopulation. To analyze the clonality of pre-lymphoma cells, various numbers of TL-2+ thymocytes from a single irradiated mouse were intra-thymically injected to Thyl congenic recipient mice. The incidence of donor type thymic lymphoma(s) was subsequently examined in a group of recipient mice. We chose several lymphomas derived from a single donor mouse and analyzed the TCR gene rearrangements and V(D)J junctional diversity as genetic markers of clonality. These results indicate multiple initial neoplastic events and clonal selection into lymphoma.

Amino Acid Sequence↗
PubMed1993

Mouse germline transcript of TCR alpha joining region and temporal expression in ontogeny.

The genetic element 'T early alpha' (TEA) in humans is located immediately 5' to the most upstream joining segment (phi J alpha) of the TCR alpha chain locus. The TEA transcript is present early in thymocyte ontogeny and the TEA-associated deletion of the TCR delta locus (delta Rec/phi J alpha rearrangement) precedes V alpha/J alpha rearrangement. We detected a 1.8 kb transcript homologous to human TEA that is spliced to C alpha in mouse thymic lymphomas showing concomitant rearrangement and expression of TCR gamma, delta, beta, and alpha. The TEA expression was highest in day 17 fetal thymocytes and declined thereafter. This expression parallels the TCR delta gene expression which is preceded by TCR gamma expression, and followed by the expression of TCR beta and alpha genes.

Animals↗
PubMed1993

Comparison of the age- and tumor-associated changes in the c-myc gene methylation in mouse liver.

Study of DNA methylation of the c-myc gene in liver tumors of BCF1 mice treated with various agents revealed frequent alteration from that in normal liver. The alteration, however, was complex and showed either an increase or a decrease of methylation to various degrees. On the other hand, the tumors obtained from middle-aged C3H/He mice, which develop liver tumors spontaneously at a high incidence rate starting in middle age, showed predominantly increases of methylation in the c-myc gene, while the large tumors found in older mice revealed decreases. The normal part of the liver showed a slight gradual age-dependent increase. These suggest that hypermethylation of the c-myc gene is common to aging and early tumor development in liver. Thus the alteration of DNA methylation seems to be a good clue to investigate why the tumor incidence rate increases rapidly as individuals grow older.

Aging↗
PubMed1993

Friend leukemia virus-induced leukemogenesis in fully H-2 incompatible C57BL/6-->C3H radiation bone marrow chimeras.

Resistance and/or susceptibility for Friend leukemia virus (FLV)-induced leukemogenesis was examined in the fully H-2 incompatible C57BL/6 (B6)-->C3H radiation bone marrow chimeras (RBMC). The results indicated that B6-->C3H chimeras never developed FLV-induced leukemias when infected with FLV 4 months after bone marrow transplantation (BMT). Spleen cells from B6-->C3H chimeras that were preimmunized with 100 Gy-irradiated FBL-3 cells (FLV-induced leukemic cell line originated from B6 mice) were shown to generate anti-FBL-3 specific T-cell proliferation as well as cytotoxic T cells. We also found that when bone marrow cells from B6 mice were mixed with those from C3H mice and then grafted into supralethally irradiated C3H mice, resulting chimeras whose peripheral blood contained less than 30% C3H-derived (susceptible) cells were refractory to FLV-induced leukemogenesis. On the other hand, when C3H mice were infected with FLV and then supralethally irradiated 5 days later and grafted with bone marrow from B6 donors, they developed leukemias which were of B6 origin. Athymic nu/nu mice of B6 background were again shown to develop leukemia following infection with FLV. Possible implication of these findings on the role of T cell-mediated immune response in resistance to FLV-induced leukemogenesis and the immunocompetent nature of fully H-2 incompatible RBMC were discussed.

Animals↗
PubMed1992

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↗
PubMed1991

Graft-versus-leukemia effect in MHC-compatible and -incompatible allogeneic bone marrow transplantation of radiation-induced, leukemia-bearing mice.

Manifestation of graft-versus-leukemia (GVL) effect in MHC-compatible and -incompatible, allogeneic bone marrow transplantation and the roles of T cell subsets contaminated in the donor bone marrow were studied using radiation-induced leukemia-bearing C3H mice maintained under specific-pathogen-free (SPF) condition. The results indicated that BMT from MHC-incompatible allogeneic (B10) donor significantly improved the survival of the treated mice as compared with that from syngeneic (C3H) donor. When donor (B10) bone marrow cells were treated with either anti-Thy 1.2 or anti-Lyt 2.2 antibody plus complement prior to BMT, a beneficial GVL effect was completely abolished. On the other hand, BMT from MHC-compatible allogeneic donors (B10.BR, CBA, AKR) failed to show an improvement in survival. However, intentional enhancement of GVH reaction by preimmunization of B10.BR donor mice with a relatively small number (10(4) approximately 10(5] of C3H spleen cells or by an addition of B10.BR lymph node cells to the donor bone marrow resulted in a significant improvement in survival. The depletion of all T cells completely abrogated the GVL effect, while the depletion of either Lyt 2+ or L3T4+ T cells from donor (B10.BR) bone marrow resulted in only partial, if any, abrogation of GVL effect. The results indicate that GVL effect observed in leukemic mice treated with allogeneic BMT from MHC-compatible (B10.BR) and -incompatible (B10) donors was totally dependent on T cells contaminated in the donor bone marrow, and suggest that the roles of T cell subsets in the induction of GVL effect were different between MHC-compatible (B10.BR) and -incompatible (B10), allogeneic BMT.

Animals↗