The influence of distance on registration in ISO-C-3D navigation: a source of error in ISO-C-3D navigation.

Computer-assisted treatments have become increasingly common. Consequently, there is an increased desire for navigation methods with simplified workflow. Anatomic-based pair-point registration is often mentioned as a source of error. Alternatively, the use of preoperatively implanted markers for registration remains complex. The self-acting registration of Iso-C-3D at the moment of data acquisition can reduce essential errors. The aim of this study was to evaluate the effect of reference placement on accuracy, and to determine the maximum acceptable distance between the reference and a given isocentre. This study demonstrates the interdependence of the reference distance on the region of interest (ROI). The mean error of registration amounts to 0.04 mm (0.04-0.05 mm) up to a distance of 200 mm and beyond 0.25 mm (0.24-0.26) for distances beyond 200 mm. The accuracy was significantly lower (p<0.0001) with a distance more than 200 mm. For optimal accuracy when utilizing navigation for pelvic and long bone surgery, the reference base should not been placed at a distance more than 200 mm from the isocentre of interest.

Preadministration of a T-suppressor factor enhances tumor immunity in DBA/2 mice.

Previously we have described the isolation and characterization of a T-suppressor factor (TsF) from a T cell hybridoma (A10F), which has a degree of specificity for the DBA/2 mastocytoma P815. Administration of A10F intravenously at the time of tumor cell injection resulted in an accelerated rate of tumor growth, decreased cytotoxic T lymphocyte antitumor activity, and reduced survival time. In the work reported here, we have shown that administration of affinity-enriched A10F 7-14 days prior to tumor cell injection causes what appear to be reverse effects, in that an enhanced resistance to the P815 tumor is observed in vivo, an effect which we can correlate with the demonstration of antitumor cytotoxic T lymphocyte activity in vitro. These effects are dose-dependent since only doses of TsF at 20 micrograms or greater are effective. A similar effect was found when A10F was administered to DBA/2 mice 10 days prior to challenge with two unrelated tumors (L1210 and M-1). However, when another TsF (Fd11F) with apparent specificity for a nominal antigen was tested in this system, it had no effect on tumor growth.

Isolation of a T-cell clone that reacts with both antigen and anti-idiotype: evidence for anti-idiotype as internal image for antigen at the T-cell level.

T-cell lines were derived from ferredoxin nonresponder B10.D2 mice that share an idiotype expressed by a monoclonal antibody (Fd-B2) with specificity for one of the two major antigenic determinants (the C determinant) of the antigen. The T-cell line and T-cell clones derived from it release interleukin 2 not only in the presence of anti-Fd-B2 idiotype antibody but in the presence of ferredoxin. The line was shown to be major histocompatibility complex-restricted in that it would respond to the anti-idiotype and antigen only in the context of presentation by cells of the H-2d haplotype. This observation also establishes that the nonresponder status of H-2d animals cannot be attributed to a lesion at the level of antigen presentation. Analysis of the fine specificity of one idiotypic clone showed that it responded only to the anti-idiotype or products of the antigen containing the C determinant, since enzymatically degraded peptides devoid of this determinant did not stimulate these cells. Furthermore, it was found that presentation of both the antigen and the anti-idiotype to the specific clone could be blocked by the Fd-B2 monoclonal antibody.

Immunization of DBA/2 mice with a T cell hybridoma-derived TsF increases immune resistance to the syngeneic tumors P815 and L1210.

The ability of a tumor-specific T suppressor factor (TsF) isolated from a T cell hybridoma, A10, to act as an immunogen in DBA/2 mice was investigated. The TsF was affinity purified from ascites over an immunoadsorbent column containing a monoclonal antibody (B16G) that has specificity for the TsF molecule, or over columns containing membrane extracts of the P815 mastocytoma (the tumor for which A10 is specific). The specificity control was BW5147 (the fusion partner for A10) membrane extracts treated in the same way as A10. DBA/2 mice were immunized with the affinity-purified material or PBS and were subsequently challenged with either the P815 tumor or the L1210 DBA/2 thymoma. When mice were immunized with material affinity purified over B16G, eluted material from both A10 ascites and BW5147 membrane extracts enhanced resistance to both P815 and L1210 challenge, indicating that B16G was binding immunogenic material derived from both preparations, which exerted a tumor-protective effect. However, when a P815 affinity column was used, protective material was eluted only from A10 ascites, and this bestowed resistance to both P815 and L1210. When irradiated whole cells were used as immunogens, only A10 cells stimulated anti-tumor immunity, and this appeared to be directed specifically to the P815 tumor. The implications of these findings in terms of the potential for immune modulation with anti-suppressor therapy, and the specificity of the B16G monoclonal, are discussed. The demonstration of B16G binding material (TsF) in the membranes (but not the ascites) of the BW5147 line is also of significance to investigators using BW5147 fused suppressor hybridomas.

Abrogation and reconstitution of nonresponsiveness: a correlation with high network connectivity.

A monoclonal antibody (Fd-B2) to ferredoxin, which bears an idiotype scarcely expressed in any of a wide variety of mouse strains, is able to markedly enhance the response to ferredoxin of both high-responder and intermediate-responder strains. A rabbit anti-idiotype serum to Fd-B2 also specifically enhances the response to ferredoxin in such mice. Most remarkably, the treatment of nonresponder T cells by either the idiotype (Fd-B2) plus complement or anti-idiotype antiserum plus complement causes them to be responsive in adoptive transfer experiments. The two responding populations (idiotype-treated and anti-idiotype-treated) can then be combined to reconstitute the nonresponsive state. When the nonresponders are treated with either Fd-B2 idiotype plus complement or anti-idiotype plus complement and subsequently respond, the idiotype of the anti-ferredoxin antibody produced does not bear the Fd-B2 idiotype. We interpret the results as being consistent with a model in which the unresponsive state for ferredoxin is a state of high network connectivity of the ferredoxin-specific T cells.

Evidence for the presence of idiotype-bearing regulatory T cells in which idiotype expression does not show linkage to either IgH alleles or the MHC.

An anti-idiotypic antiserum was raised in rabbits to a monoclonal antibody with specificity for one of the two antigenic determinants on the ferredoxin (Fd) molecule. The monoclonal antibody (Fd-B2) was derived from fusion of spleen cells from Fd-immune B10.BR (H-2k, Ighb). Examination of an extensive number of samples of Fd-immune serum from B10.BR and other mouse strains established that the Fd-B2 idiotype is essentially never present in such sera in detectable concentrations (greater than 30 ng/ml). Administration of the anti-idiotypic antibody (anti-Fd-B2) i.v. to B10.BR mice, or treatment of B10.BR T cell-enriched populations with anti-Fd-B2 + C prior to adoptive transfer to irradiated B10.BR recipients followed by challenge with Fd resulted in a significant increase in the production of anti-Fd antibodies. This effect was specific and was not reflected by a change in expression of the Fd-B2 idiotype in the antibody produced. Similarly, injection of 10 micrograms of Fd-B2 into B10.BR mice resulted in an enhanced anti-Fd response. When similar experiments were carried out using B10.D2 mice (H-2d, Ighb), which are genetic non-responders to Fd, it was observed that treatment which anti-Fd-B2 followed by challenge with Fd resulted in production in treated animals of significant levels of antibody to Fd. Again, the antisera thus produced did not contain detectable levels of the Fd-B2 idiotype. Further experiments using high responder (H-2k) mice with Igh allotypes differing from the B10 strains (C57/BR, Igha, and RF/J, Ighc), showed that treatment of these animals with anti-Fd-B2 also resulted in a highly significant enhancement of the anti-Fd response. These data imply that the anti-idiotypic antiserum (anti-Fd-2B) is exerting its influence by acting on an id + population of T cells and that the expression of this id is not dependent on genetic linkage to either the H-2 or the Igh loci.

Identification of an idiotypic marker of a major regulatory T cell of the immune response in B10.BR mice to ferredoxin. The relationship of idiotypic regulation to conventional hapten-carrier effects.

An anti-idiotypic antiserum was raised in rabbits to a monoclonal antibody (Fd-1) with specificity for one (the N epitope) of the two antigenic epitopes found on the ferredoxin (Fd) molecule. The anti-idiotypic antiserum (anti-Fd-1) was used to demonstrate that the Fd-1 idiotype was expressed at significant levels in most anti-Fd antisera raised in B10.BR mice. Examination of antisera raised in other mouse strains demonstrated that expression of this idiotype mapped to the IgH gene complex and was found in the antisera of all mouse strains examined with the Ig-1 allotype. When splenocytes from Fd-immune B10.Br mice were treated with anti-Fd-1 and transferred to irradiated syngeneic recipients, the adoptive secondary response was significantly higher in animals receiving treated cells as opposed to control animals, which received normal rabbit serum-treated cells. This response produced a net increase in antibody to both determinants, and the relative amount of Fd-1 idiotype was not significantly altered. Further studies with separated cell populations showed that the overall increase of anti-Fd antibody produced was attributable to the effects of the anti-idiotypic serum on a population(s) of T cells. Treatment of mice with the Fd-1 monoclonal antibody (which should react with anti-idiotypic cells) had an analogous effect to that of the anti-idiotype, in that mice so treated produced higher concentrations of anti-Fd antibodies when they were immunized and these antibodies exhibited net increases to both determinants. A model is presented to explain these results.