Cell-mediated immunity to histocompatibility antigens : controlling factors, with emphasis on Graft-versus-host reactions in mice

Graft-versus-Host (GvH) disease is characterized by weight loss, diarrhea, skin lesions, hypofunction of the immune system with concomitant infections, etc. This syndrome is potentially lethal. GvH reactions, which underly this disease, may occur when immunocompetent T lymphocytes are transplanted into a host, which is unable to eliminate the intrusive donor lymphocytes and which confronts the graft with a sufficient degree of histoincompatibility. The type of T lymphocyte which plays a central role in GvH reactions seems to be the Lyt-1+ T cell, which probably is analogous to the helper T cell. This cell type may activate other subsets of T lymphocytes, viz., cytotoxic T cells and suppressor T cells, which may lead to GvH disease, depending on the experimental conditions and antigenic differences between donor and host, The GvH reaction is not only interesting from the point of view of the ensuing syndrome, but can also be used to study certain fundamental immunological problems, such as which histocompatibility antigens evoke the strongest immune reactions, which cell types are involved, do these cell types synergize, etc. We approached these questions in experimental studies with mice. To study such problems one has to have an appropriate assay. We made use of a delayed-type hypersensitivity (DTH) assay which is appropriate to measure the anti-host immune reactivity during acute and delayed GvH reactions in mic

Fixed priority scheduling with pre-emption thresholds and cache-related pre-emption delays: integrated analysis and evaluation

Commercial off-the-shelf programmable platforms for real-time systems typically contain a cache to bridge the gap between the processor speed and main memory speed. Because cache-related pre-emption delays (CRPD) can have a significant influence on the computation times of tasks, CRPD have been integrated in the response time analysis for fixed-priority pre-emptive scheduling (FPPS). This paper presents CRPD aware response-time analysis of sporadic tasks with arbitrary deadlines for fixed-priority pre-emption threshold scheduling (FPTS), generalizing earlier work. The analysis is complemented by an optimal (pre-emption) threshold assignment algorithm, assuming the priorities of tasks are given. We further improve upon these results by presenting an algorithm that searches for a layout of tasks in memory that makes a task set schedulable. The paper includes an extensive comparative evaluation of the schedulability ratios of FPPS and FPTS, taking CRPD into account. The practical relevance of our work stems from FPTS support in AUTOSAR, a standardized development model for the automotive industry

System Architecture for 3D Gravity Modelling

A flexible software architecture for gravity modelling is establishedand the advantage is discussed of having several alternative programs tohandle complex 3D models. The flexible architecture consists of four parts, implemented in a distributed computer environment:the three-dimensional model builders and visualizers (GOCADsoftware, version 7.0), the model representation translators (GOCADsoftware or GEOMOD sofware), the forward simulation algorithmsof gravimetric data (alpplying Talwani-Ewing and Goetze- Lahmeyermethods in the finite-element representation class), and the inversion(model updating) scheme manager based on the Cordell - Hendersoninversion procedure.A good software architecture should at least keep the model building and updating software separate from the forward simulation software. Inversion schemes can then be realized by communication between the two parts of software.Several synthetic cascs are shown to demonstrate the use and thecapability of the architecture and methods applied. The gravity fieldsof complex 3D models, i.e. overhanging and non-overhanging saltdomes, are simulated. The gravimetric anomalies for both cases havevery similar shapes. Gravity modelling can distinguish between these,because the existing mass differences result in anomaly differencesboth for surface profiles and X-sections. The capability of the inversionprocedure is also shown in the discussed synthetic case. The inversion manager is able to create the global structural forms representedas a horizon with constant density contrast (a two-layer model) from residual gravity anomalies.</div

Immunomagnetic t-lymphocyte depletion (ITLD) of rat bone marrow using OX-19 monoclonal antibody

Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (0×19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival. A highly efficient technique of T-lymphocyte depletion using rat bone marrow is described. It involves the binding of OX-19, a MoAb directed against all rat thy-mocytes and mature peripheral T lymphocytes, to monosized, magnetic polymer spheres. Magnetic separation of T lymphocytes after mixing the allogeneic bone marrow with the bead/OX-19 complex provides for a simple, rapid depletion of T lymphocytes from the bone marrow. In vitro studies using flow cytometry and the prevention of GVHD in a fully allogeneic rat bone marrow model have been used to demonstrate the effectiveness of the depletion procedure. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice

A murine model for acute lethal graft vs. host disease (GVHD) was used to study the role that a number of cytokines play in the development of lethal GVHD. In this study we focused on the role of IL-1, IL-2, IL-4, IL-6, IFN-γ and TNF-α. Lethally irradiated (C57BL × CBA)F1 mice were reconstituted either with 107 allogeneic BALB/c spleen cells or with a similar number of syngeneic cells, as a control. A significant rise in serum levels of IL-6, TNF-α and IFN-γ levels was found in allogeneically reconstituted mice. This is in contrast to the syngeneic control group in which no rise was seen. Serum IL-2 and IL-4 levels were below the detection limit. In the supernatant of Con A stimulated spleen cells from allogeneically reconstituted mice IL-6, IFN-γ and TNF-α concentrations were increased. The expression of mRNA for cytokines as detected by reverse transcription PCR was studied in spleen cells. In the allogeneic reconstituted mice the mRNA expression of IL-1α, IL-2, IL-6, IFN-γ and TNF-α displayed faster kinetics compared with that in syngeneic reconstituted mice. The effect of treatment with recombinant cytokines, antibodies to cytokines and to cytokine receptors on the development of GVHD was investigated. Administration of recombinant IL-2 to allogeneically reconstituted mice strongly increased the morbidity and mortality whereas injection of IL-1α and TNF-α did not influence survival. Administration of antibodies against IL-2 or the IL-2 receptor decreased the morbidity and mortality. Anti-IL-6, anti-IFN-γ, and anti-TNF-α mAB, on the other hand, did not affect the morbidity and mortality of GVHD. The results of this study suggest successive waves of cytokine-secreting cell populations consistent with the induction of an inflammatory response in the development of acute GVH disease

Validation of skeletal muscle mass assessment at the level of the third cervical vertebra in patients with head and neck cancer

Background: Low skeletal muscle mass (SMM) is associated with adverse outcomes. SMM is often assessed at the third lumbar vertebra (L3) on abdominal imaging. Abdominal imaging is not routinely performed in patients with head and neck cancer (HNC). We aim to validate SMM measurement at the level of the third cervical vertebra (C3) on head and neck imaging. Material and methods: Patients with pre-treatment whole-body computed tomography (CT) between 2010 and 2018 were included. Cross-sectional muscle area (CSMA) was manually delineated at the level of C3 and L3. Correlation coefficients and intraclass correlation coefficients (ICCs) were calculated. Cohen's kappa was used to assess the reliability of identifying a patient with low SMM. Results: Two hundred patients were included. Correlation between CSMA at the level of C3 and L3 was good (r = 0.75, p < 0.01). Using a multivariate formula to estimate CSMA at L3, including gender, age, and weight, correlation improved (r = 0.82, p < 0.01). The agreement between estimated and actual CSMA at L3 was good (ICC 0.78, p < 0.01). There was moderate agreement in the identification of patients with low SMM based on the estimated lumbar skeletal muscle mass index (LSMI) and actual LSMI (Cohen's κ: 0.57, 95%CI 0.45–0.69). Conclusions: CSMA at C3 correlates well with CSMA at L3. There is moderate agreement in the identification of patients with low SMM based on the estimated lumbar SMI (based on measurement at C3) and actual LSMI