[Non-immunologic functions associated with the MHC].
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Biomedical subjects
Publications and source records attributed to M Pla.
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Two radiosurgical procedures using a stereotactic frame and a linear accelerator X ray beam with a circular field diameter between 0.5 and 3 cm are presented. One technique is based on a single plane rotation (single plane radiosurgery) whereas the other uses simultaneous and continuous motions of both the gantry (approximately 360 degrees) and couch (approximately 180 degrees) during the radiosurgical procedure (dynamic radiosurgery). The dose, typically a few thousand cGy, is prescribed to the 90% isodose line which just covers the target volume. The dose fall-off outside the spherical target volume is considerably sharper for the dynamic rotation than for the single plane rotation, and is comparable to the dose fall-off obtained with the two presently known dedicated radiosurgical techniques: one based on focused cobalt beams and the other on proton beams. The dose fall-off in the dynamic radiosurgery discussed here is also comparable to that of previously described linear accelerator based multiple converging are techniques, making the dynamic radiosurgery an attractive alternative to presently known radiosurgical procedures. The radiation beam parameters are discussed and the stereotactic frame described. The dose distributions for both radiosurgical techniques are calculated in a single plane and then corrected for the attenuation effects in the stereotactic frame (approximately 2%) and for the effects of the dynamic rotation (approximately 2%). The skin doses are 0.7% and 2%, and the lens doses, if the beam passes through the eyes, are 2.5% and 3.5% for the dynamic rotation and single plane rotation, respectively. The scatter and leakage dose for the radiosurgical procedures is typically 0.2% to the patient's thyroid, 0.06% to the breast, and 0.02% to the gonads.
Purified allogeneic murine platelet suspensions were found unable to induce primary anti-H-2 class I antibody or T cell proliferative responses. In contrast, the same platelet suspensions could elicit secondary anti-class I responses. The secondary responses were not due to contaminating leucocytes. Possible explanations, the lack of acolyte determinants (class II or non- H-2) on platelets or inappropriate layout and/or structure of their class I antigens, are discussed. These findings emphasize the importance of sufficient leucocyte depletion before platelet transfusion in the human.
Mice pretreated with injections of allogeneic platelets were found to mount a decreased antibody response upon challenge by lymphocytes of the same donor strain. This decrease was mediated by platelets themselves, and not by leucocytes and red cells contaminating the platelet suspension. It affected specifically antibodies reactive with H-2 class I antigens present on donor platelets. This phenomenon may be related to the lack of class II or some non-H-2 antigens on platelets, and/or to properties of their class I antigens (soluble molecules adsorbed from the plasma). These findings emphasize the potential usefulness of purified platelet transfusions preceding organ transplantation in man.
The ability of mice to clear Salmonella typhimurium from their spleens in the late phase of infection was studied after inoculation with a temperature-sensitive mutant. Clearance of bacteria was delayed in C57BL/6 mice compared with BALB/c, C3H/HeJ, DBA/2, A/J, and CBA mice. The responses of F1 hybrids, backcrosses, and recombinant inbred strains derived from C57BL/6 and BALB/c (both Itys) and of H-2 congenic mice were analyzed. The results showed that the low rate of bacterial clearance was recessive, that the rate of clearance was under polygenic control, and that an H-2-linked gene(s) plays a major role. Among H-2 congenic mice with a C57BL/10 background, three phenotypes of bacterial clearance could be distinguished: high (H-2j, H-2q, and H-2u), intermediate (H-2d, H-2f, H-2k, H-2p, H-2r, H-2s, and H-2v), and low (H-2b) rates. The effect of the H-2 complex was apparent with different genetic backgrounds (Itys and Ityr). In recombinant inbred strains derived from C57BL/6 (Itys) and A/J (Ityr) mice, the effect of the H-2b haplotype on bacterial clearance appeared to be fully expressed only in strains carrying the Itys allele.
The capacity of the B cell immunoglobulin receptor to recognize complexes of Sendai viral and H-2b antigens was investigated by studying the antibody response to injections of syngeneic Sendai virus-coated (SV+) spleen cells in C57BL/6 (B6) mice. Almost all mice produced alloreactive anti-H2 lymphocytotoxic antibodies. In contrast, such antibodies were found very exceptionally in mice injected with normal (SV-) cells or with Sendai virus (SV) only. The reaction pattern of the cytotoxic antibodies induced was variable and ranged from almost anti-private to widely cross-reactive serotypes. The results of reactions on H-2-congenic, -recombinant and -mutant mouse strains, and of capping and immunoprecipitation experiments showed that the cytotoxic antibodies were directed against H-2 class I molecules. The anti-H-2 antibodies exhibited enhanced binding for SV+ target cells, but absorption experiments showed that this was not the result of cross-reactions with cell surface Sendai viral determinants or with a molecular complex of H-2 plus SV. This conclusion was supported by the observation that syngeneic SV+ cells were not the predominant targets for the induced lymphocytotoxic antibodies. Our results do not support the existence of MHC-restricted antiviral antibodies, but show the induction of anti-class I H-2 alloantibodies by injections with syngeneic SV-coated cells. We present a model for regular induction of anti-H-2 antibodies without intentional alloimmunization.
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Dynamic stereotactic radiosurgery is a radiosurgical technique based on a medium-energy isocentric linear accelerator and a stereotactic frame. The technique uses concurrent and continuous rotations of both the gantry (300 degrees, from 30 to 330 degrees) and the couch (150 degrees, from 75 to -75 degrees). It gives a uniform dose (+/- 5%) within the target volume and dose fall-offs outside the target volume comparable to those obtained from presently known radiosurgical techniques.
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A genomic cosmid library constructed from DNA from a genotyped individual (JF = HLA-A11, Cw-, B38/A26, Cw7, B51) was screened for clones containing class I histocompatibility genes. Among these clones, one was found to carry a 4.8 kb Hind III fragment which is highly correlated with HLA-A11. This clone was used to transfect LMTK+ cultured mouse fibroblast transformants expressing human beta-2 microglobulin. The human beta-2 microglobulin heavy chain-associated determinant was positively detected by the M18 monoclonal antibody. HLA-A11 expression on these doubly transformed cells was specifically demonstrated by complement-dependent cytotoxicity with HLA-A11 + A3-specific but not with HLA-A3-specific monoclonal antibodies. Absorption studies with human alloantisera confirmed the presence on these cells of HLA-A11 determinants and of cross-reacting determinants which absorbed anti-HLA-A1 and -A3 alloantisera. The JF5-J27 transfected cell expressed both heavy and light chains of human class I histocompatibility genes.
The physics measurements on a Selectron high dose-rate afterloading cobalt-60 unit are reported. The installation was found to be acceptable from the standpoint of radiation safety and cost effectiveness; hospital bed space was saved as treatment could be on an outpatient basis. A source calibration 4% higher than the value stated by the manufacturer was obtained. Measurement of the ratio of exposure rate in water to that in air confirmed the calibration and the applicability of correction factors for routine clinical dosimetry recommended in the literature.
Several experimental data suggest that, compared with other organs, the liver has a privileged status as concerns rejection. In fact, in pigs and rats, spontaneously tolerated liver allografts have been observed with, in rats, constitution of a state of donor-specific transplantation tolerance. Hyperacute rejection, which is a complication of organ allografts in some immunological situations, has not been observed after liver transplantation. In man, acute rejection of liver allografts usually is easily controlled by the immunosuppressive treatment. However, in some cases, an irreversible chronic rejection may occur.
A monoclonal antibody known to recognize the H-2.m3 specificity is shown to react with the class I H-2 product of tLub-1 but not tw12tf mice. This reagent was used to study the segregation of the H-2 complex in the progeny of tLub-1 +/tw12tf females. The most straightforward interpretation of the results presented here is that these t haplotypes carry an H-2 complex located between the centromere and tufted locus. Possible consequences of such a location with regard to the recombination between t haplotypes and chromosome 17 from laboratory mice are discussed.
A simple rotational total skin electron irradiation technique utilising a single large field electron beam is presented. Clinical and technical aspects of the technique are discussed and treatment results for the first 10 patients treated for widespread mycosis fungoides reported. The technique is simple and well tolerated by patients, and can easily be implemented in centres utilising electron beam radiotherapy.
A technique for total body irradiation, in which the patient lies in the prone or supine position in the beam of a conventional column mounted 4 MV linear accelerator, is described. A sufficiently large radiation field is obtained by rotating the beam in a vertical plane about the source (i.e., sweeping beam) at a source-to-skin distance of 190 cm on the vertical axis. The variation of the midplane dose is less than +/- 5% in parallel-opposed beams, when attenuators are placed over the region containing the lungs and bolus is employed around the head and legs. The percentage depth dose for the sweeping beam is identical to that of a stationary beam for the same collimator setting and source-to-skin distance. A method for monitoring the dose to the patient by means of a thimble ionization chamber located on the vertical beam axis is outlined. The average dose rates used are between 5 and 10 cGy/min. The design and placement of lung attenuators is simple. The treatment technique with the sweeping beam requires minimal modification of a treatment unit and can be applied on any unit which has a head swivel option.
Serologic evidence for the existence of beta 2-microglobulin-, (beta 2m) like and H-2-like antigenic determinants in Drosophila are presented. Drosophila-cultured cells and larvae extract were shown to react specifically with a rabbit anti-rat beta 2m and a rabbit anti-mouse beta 2m antisera. G-200 pooled fractions from Drosophila larvae were shown to react with beta 2m-eluted and glycin-absorbed antisera, but not with beta 2m-absorbed or glycin-eluted antisera. These fractions also quantitatively inhibited the heterologous reaction between the anti-beta 2m antisera and purified human and rat beta 2m. The lack of reactivity of other rabbit antisera or normal serum with Drosophila, as well as the efficiency of absorption of anti-beta 2m reactivity by either rat or KCO% (Drosophila) cells, further supports the presence of beta 2m epitopes on Drosophila cells. Data are also presented showing that certain anti-H-2 alloantisera react with Drosophila. That this reactivity is indeed due to anti-H-2 antibodies is suggested by several lines of evidence, including the removal of cytotoxic alloantibodies and lack of reactivity by other mouse antisera and monoclonal reagents. Preliminary data suggest that the H-2-like and beta 2m-like determinants are physically associated on the cell surface of Drosophila cells. These findings have important implications on current concepts concerning the evolutionary origin and physiologic role of beta 2m and the major histocompatibility complex.