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Biomedical subjects

M Usui

Publications and source records attributed to M Usui.

At least 325 records · Page 18Linked to original sources
PubMed1984

Requirements for suppressor T cell activation.

Third-order (Ts3) suppressor cells are generated after conventional immunization. These cells, however, will not mediate suppressor cell function unless specifically triggered by an activating signal, termed TsF2. This report analyzes the mechanism of this TsF2-mediated triggering event. TsF2-mediated suppression is genetically restricted by genes in the I-J and Igh-V regions. The target of the I-J restrictions is a firmly adherent accessory cell, which appears to express I-J-related determinants. These accessory cells are sensitive to cyclophosphamide treatment and 500 R irradiation. In contrast, the target of the Igh-V restriction of TsF2 appears to be the Ts3 cell, which carries antigen-specific, idiotype-related receptors. The mechanism of suppressor cell activation appears to involve two stages. Presentation of I-J-restricted TsF2 by I-J-compatible presenting cells and a second step involving idiotype-anti-idiotype interactions between TsF2 and the Ts3 cell. I-J compatibility is not required with the accessory cell for Ts3 activation. Finally, we hypothesize that the anti-idiotypic determinants expressed on TsF2 can serve as an internal image of antigen, thereby permitting specific targeting of the factor.

Animals↗
PubMed1984

A role for macrophages in suppressor cell induction.

A mechanism responsible for the induction of NP-specific first order (inducer) suppressor cells (TS1) is described. TS1 cells are induced by i.v. administration of hapten-coupled splenic cells. Their activity is assessed by the adoptive transfer of NP-specific suppression during the afferent phase of the contact sensitivity response. NP-coupled firmly adherent, FcR+, I-A-bearing macrophages induce TS1. The antigen-presenting cells required for TS1 induction lack the Thy-1 and Lyt-1 markers, and are resistant to 500 R irradiation and to cyclophosphamide treatment. NP-coupled dendritic cells fail to induce TS1 activity. The induction of TS1 cells is genetically restricted by genes that map in the I-J region of the H-2 complex. The NP-coupled antigen-presenting cells must share at least one I-J allele with the TS1 donor for effective induction of TS1 activity. To minimize allogeneic effects in these studies, the activity of the TS1 population was assessed by adoptive transfer into syngeneic recipients. The present results are compared with the mechanisms required for the induction of second and third order suppressor cells.

Animals↗
PubMed1984

A genetically restricted suppressor factor that requires interaction with two distinct targets.

We have previously described a genetically restricted suppressor factor (TsF3) that suppresses the terminal phases of the contact sensitivity response. The activity of TsF3 is restricted by genes in the H-2 (I-J) and Igh complexes. This report analyzes the mechanisms responsible for these genetic restrictions. One cellular target of TsF3 is an I-J-bearing antigen-presenting cell population that is sensitive to low doses of cyclophosphamide. To elicit suppression I-J homology is required between this antigen-presenting cell population and the TsF3 donor. In contrast, the Igh-linked genetic restriction exists between TsF3 and an unprimed cell population present in the recipient. These findings suggest that under these experimental conditions TsF3 acts by bridging the APC with cells of the host. Finally, we demonstrated that nonspecific bystander or cognate suppression can be mediated by TsF3, provided specific antigen is present in the site of the ongoing T cell response.

Animals↗
PubMed1984

The expression of idiotypic determinants on suppressor T cells is independent of T cell Igh genotype.

To investigate the role played by immunoglobulins in the display of idiotope-like determinants by T cells, we investigated whether T cells transferred to congenically athymic mice would display the idiotypes of the nude host or of the T cell donor Igh genotype. 4-Hydroxy-3-nitrophenyl hapten (NP)-specific first-order suppressor T cells (Ts1) from Ighb-bearing mice display the NPb idiotype. Mature peripheral T cells from Igh congenic mice were used for reconstitution of nude mice in acute transfers. Before analyzing the idiotypic properties of the T cells in this system, we verified, using Thy-1 congenic strains, that the suppressor T cells induced were effectively derived from the transferred T cells and not from the host. The following strains of mice were selected for these studies: C57BL/6 (Ighb), B6.Ighn, and C57BL nu/nu. The NP-specific suppressor T cells generated in C57BL nu/nu mice reconstituted with T cells derived from Igh congenic B6.Ighn donors were investigated. Suppressor T cells were induced by i.v. administration of 10(4) NP-coupled B6.Ighn adherent cells. Six days later, the spleen cells from the reconstituted nude mice were treated with anti-NPb antibodies and complement before being transferred to C57BL/6 recipients immediately prior to antigen priming. Treatment with anti-idiotypic reagents depleted suppressor cell activity, which indicates that the suppressor cells obtained from C57BL/6 mice or C57BL nu/nu mice that have been reconstituted with B6.Ighn T cells bear NPb idiotype-related determinants. The data further demonstrate that the idiotype-related determinants expressed on NP-specific Ts1 are controlled not by the Ighn genotype of the T cell donor, but by the genotype of the C57BL nu/nu (Ighb) recipient host. In agreement with these findings, we further verified that the NP-specific suppressor T cells generated in C57BL nu/nu mice reconstituted with B6.Ighn mature T cells display the operational Igh restrictions of C57BL/6 mice and not of B6.Ighn mice. These experiments demonstrate how idiotypic elements expressed on the immunoglobulins of the host influence the specificity of the antigen receptor on T cells. Normally, Ts1 from B6.Ighn mice lack the NPb idiotype-related determinants and their suppressive activity is operationally restricted by the Ighn allotype. However, mature B6.Ighn T cells selected to respond to NP in C57BL nu/nu recipients display idiotype-related determinants and restriction specificities characteristic of the C57BL (Ighb) host. Thus, the environment in which Ts1 are induced and selected affects the Ts1 repertoire. How can we account for this phenomenon?

Animals↗
PubMed1984

[A histological study on osteosarcoma. Part I: Relationship between modes of osteoid formation and differentiation of tumor cells].

This study was undertaken to clarify whether the osteoid forming activity seen in osteosarcoma can be used as an index to show the degree of differentiation of the tumor. Twenty six human osteosarcomas which had been amputated in our clinics were used in this study. The whole slice of the primary tumor was stained by HE and Masson stain. The following observations were microscopically made in the peripheral, transitional and central part of the tumor; 1) the content and maturity of osteoid, 2) the degree of polymorphism and mitotic activity of the tumor cells. In 13 out of 26 cases, the amount and maturity of osteoid gradually increased toward the center of the tumor. On the other hand, the degree of polymorphism and mitotic activity of tumor cells in these cases gradually decreased toward the center. Mitotic activity in the center of the tumor decreased to about half of the peripheral part. The clinical courses of these 13 cases were milder than those in which the gradual increase of the amount and maturity of osteoid toward the center of the tumor were not observed. These results showed that zone formation of osteoid maturity in osteosarcoma can be used as an index to show the degree of differentiation of the tumor.

Adolescent↗
PubMed1983

The in vivo effects of various immunoreactive treatments on allogeneic tendon grafts.

The immunologic antigenicity of tendons after various treatments was investigated by means of the complement-dependent cytotoxicity test in two strains of inbred rats. Allogeneic tendons treated by various methods were grafted into rats, and the survival of the grafted tendons was observed macro- and microscopically. Paraformaldehyde-treated allogeneic tendons showed the least immunologic response. The remaining treated allogeneic tendons showed moderate to marked immunologic responses. These in vivo results correlated with those obtained in previous in vitro experiments.

Animals↗
PubMed1983

Characteristics of human soft tissue sarcomas in xenografts and in vitro.

Two permanent, transplantable strains of rhabdomyosarcoma (SAS) and synovial sarcoma (KUSHI) were established by transplanting them serially into nude mice. The original SAS tumor and its transplant were histologically identical and gave an appearance of so-called embryonal rhabdomyosarcoma. The KUSHI tumor changed after the second passage, showing the biphasic pattern of synovial sarcoma, while undifferentiated myoblast-like cells were observed throughout the original tumor. Three in vitro cell lines from the SAS and one from the KUSHI tumor were successfully established. The human origin of the SAS and KUSHI transplanted tumors could be verified by the presence of human chromosomes. The cells cultured from the SAS tumor were more sensitive to anticancer drugs than those of the KUSHI tumor. However, as the number of serial passages on nude mice increased, the sensitivities of the SAS cells decreased, while those of the KUSHI cells increased. The modal chromosome number of the SAS tumor changed from 51 to 49 to 46 during serial passages on nude mice. These observations suggest that the sensitivities to anticancer drugs not only differ among soft tissue sarcomas of different histologic types, but also change continuously during the growth of the tumor itself.

Animals↗
PubMed1983

Localization of S-antigen by enzyme-labelled antibody method and electron microscopy.

Localization of S-antigen was studied by a direct enzyme-labeled immunohistochemical method with light and electron microscopes. IgG was prepared from rabbits which were sensitized by swine retinal S-antigen and the IgG was conjugated with horseradish peroxidase (HRP). This HRP-labeled IgG was directly applied to normal rabbit retina and the retina was processed to make slides for light and electron microscopic examinations. In light microscopic findings, a clear-cut positive response was noted in the outer segment of photoreceptor cells which was similar to that of Wacker's observation, and a weak response was observed in the inner segment of the photoreceptor cells and the outer nuclear layer. In electron microscopic findings, immunoprecipitates, which were represented by electron-dense particles, were observed on both sides of the disk membrane of the outer segment with evenly distributed particles on both outer and inner surfaces, showing a pattern symmetric to that of the membrane. These immunoprecipitates were also noted in the plasma membrane of the outer segment but there they did not show a pattern similar to that of the disk membrane. A small amount of pinpoint-shaped immunoprecipitates were also noted in the cytoplasm of the inner segment and the connecting cilia. The immunoprecipitates were observed to gradually decrease in number with the phagocytosis of the outer segment by the retinal pigment epithelium, and they finally disappeared as fragments which were completely phagocytized. These findings may suggest a renewal process of S-antigen and a rationalization of this theory was discussed.

Animals↗
PubMed1983

An experimental study on the effect of fluorocarbon on the preservation of free skin flaps in the rabbit.

Extensive experience with replantation and transplantation surgery has accrued since the development of microvascular surgery. However, circulation often fails to return to a tissue after a temporary period of vascular obstruction, even if the vascular anastomoses are perfect. This circulation failure is known as the "no-reflow phenomenon." The authors investigated the effectiveness of fluorocarbon (FC) in preventing this condition using the free epigastric flap of the rabbit. When the flaps were immersed in oxygenated FC during the ischemic period, the survival rate of the flap was 100% and 80% in 12 and 24 hours of ischemia, respectively. These survival rates were higher than those in control animals (20%). Although further studies are necessary for clinical application, it is suggested that the FC immersion technique has a definite potential for prevention of the no-reflow phenomenon in tissue transplantation and replantation surgery.

Animals↗
PubMed1982

Analysis of osteoid-forming activity of human osteosarcoma implanted into nude mice.

Thirty cases of human osteosarcoma were transplanted subcutaneously in BALB/c nude mice. Twenty-four tumours survived in animals and showed the histopathology of the original tumours. Growth of transplantable tumours was closely related to the amount of osteoid tissue and tumours with predominant osteoid tissue showed slow growth. Tumours whose osteoid-forming activity tended to diminish or disappear were likely to fail early during serial transplantation. Two osteosarcoma (SU and ISHI) were established into permanent transplantable strains and were maintained in nude mice for more than three years. These two strains showed striking differences in their growth capacity; SU grew rapidly and frequently formed pulmonary tumours after tail vein injection of tumour cells. Histologically, ISHI osteosarcoma cells continue to form osteoid tissue, whereas SU cells showed anaplastic changes and lost osteoid-forming activity. Alkaline phosphatase and Lactate Dehydrogenase (LDH) activities of tumour tissue were lower in ISHI than SU, and significant elevation of the relative value of Fraction III of LDH isozyme has been demonstrated in SU, and Fraction IV in ISHI. On this basis, the authors discuss the relation between the amount of osteoid formation or LDH isozyme patterns and the malignant potential of human osteosarcoma.

Alkaline Phosphatase↗
PubMed1982

Immunoglobulin E-suppressing and immunoglobulin G-enhancing tetanus toxoid prepared by conjugation with pullulan.

Immunoglobulin E (IgE) antibody response was found to be suppressed selectively and antigen specifically in mice given an antigen conjugated with pullulan, a linear copolymer of maltotriose, whereas IgM and IgG antibody responses were enhanced. On the basis of this finding, tetanus toxin was conjugated with pullulan by cyanuric chloride in the hope that the toxin would be detoxified by the conjugation procedure and could be used as an IgE-suppressing and IgG-enhancing toxoid without the aid of an aluminum adjuvant. This procedure of tetanus toxoid-pullulan conjugation apparently detoxified the toxin. Administration of the resulting tetanus toxoid, tetanus toxin-pullulan conjugate, to mice induced strong suppression of IgE antibody response with fairly good IgG response, whereas the alum-precipitated toxoid or plain toxoid, customarily used for vaccination, elicited high IgE antibody formation. The IgE antibody response was minimal, but the IgG antibody response was maximal in the conjugate-primed mice even after a booster injection with an IgE antibody-inducing dose of the alum-precipitated toxoid.

Animals↗