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Biomedical subjects

M van Gils

Publications and source records attributed to M van Gils.

8 recordsLinked to original sources

beta-chemokines and neutralizing antibody titers correlate with sterilizing immunity generated in HIV-1 vaccinated macaques.

One of the obstacles to AIDS vaccine development is the variability of HIV-1 within individuals and within infected populations, enabling viral escape from highly specific vaccine induced immune responses. An understanding of the different immune mechanisms capable of inhibiting HIV infection may be of benefit in the eventual design of vaccines effective against HIV-1 variants. To study this we first compared the immune responses induced in Rhesus monkeys by using two different immunization strategies based on the same vaccine strain of HIV-1. We then utilized a chimeric simian/HIV that expressed the envelope of a dual tropic HIV-1 escape variant isolated from a later time point from the same patient from which the vaccine strain was isolated. Upon challenge, one vaccine group was completely protected from infection, whereas all of the other vaccinees and controls became infected. Protected macaques developed highest titers of heterologous neutralizing antibodies, and consistently elevated HIV-1-specific T helper responses. Furthermore, only protected animals had markedly increased concentrations of RANTES, macrophage inflammatory proteins 1alpha and 1beta produced by circulating CD8(+) T cells. These results suggest that vaccine strategies that induce multiple effector mechanisms in concert with beta-chemokines may be desired in the generation of protective immune responses by HIV-1 vaccines.

AIDS Vaccines

Framework for biosignal interpretation in intensive care and anesthesia.

Improved monitoring improves outcomes of care. As critical care is "critical", everything that can be done to detect and prevent complications as early as possible benefits the patients. In spite of major efforts by the research community to develop and apply sophisticated biosignal interpretation methods (BSI), the uptake of the results by industry has been poor. Consequently, the BSI methods used in clinical routine are fairly simple. This paper postulates that the main reason for the poor uptake is the insufficient bridging between the actors (i.e., clinicians, industry and research). This makes it difficult for the BSI developers to understand what can be implemented into commercial systems and what will be accepted by clinicians as routine tools. A framework is suggested that enables improved interaction and cooperation between the actors. This framework is based on the emerging commercial patient monitoring and data management platforms which can be shared and utilized by all concerned, from research to development and finally to clinical evaluation.

Anesthesia

Modelling techniques and their application for monitoring in high dependency environments--learning models.

This paper reviews the use of learning models including Bayesian classifiers and artificial neural networks in monitoring and interpreting biosignals. Generally learning models applied for analysis of biosignals are "black-box' types trained on the basis of measured signals. It is illustrated that the training and application of learning models more or less follow the same sequences. The main focus is the interpretation of electrical signals from the brain (electroencephalogram (EEG) and evoked potentials (EP)). Current analysis of these signals often reveals sudden changes in the EEG or evoked potentials to be the earliest discernible signs of inadequate perfusion of the brain. They may reflect problems such as systemic arterial oxygen desaturation or hypotension arising from other body system failures during critical illness. It is suggested that these brain signals should be recorded in the critical care unit, and that they should form part of the annotated database of biosignals established during the IMPROVE project. This would allow for the development of new methods for on-line warning of impending damage to the central nervous system, such that corrective actions could be taken before permanent damage occurred.

Auscultation

Functional and molecular characterization of B cell-responsive V delta 1+ gamma delta T cells.

Cells expressing the V delta 1+ gene segment are a minor gamma delta T cell population in human peripheral blood but predominate in epithelial and (inflamed) tissues. The characteristic dendritic-like morphology of these gamma delta T cells is consistent with their putative immune surveillance role in epithelia. Their function, however, remains unknown. We and others previously reported that a subset of V delta 1+ gamma delta T cells proliferates after stimulation with Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (LCL), but not with fresh peripheral blood-derived B cells. These responses were independent of the type of T cell receptor (TcR) gamma chain co-expressed with the V delta 1 chain. The in vivo relevance of this LCL-mediated activation as well as the nature of the stimulatory ligand on the LCL is not well established. In this study, we tested the proliferative response of V delta 1+ LCL-responsive T cells against non-EBV-transformed B cells, activated through CD40 by murine EL4 B5 cells, and to a panel of B cell lines differing in the expression of EBV nuclear antigen proteins and adhesion/co-stimulatory molecules. The role of the Epstein-Barr virus-derived antigen in the induction of this response could be excluded as the activated (non-EBV-transformed) peripheral blood B cells were also able to induce a proliferative response in the LCL-responsive V delta 1+ T cells. Therefore, the stimulatory ligand on B cells is of cellular rather than of viral origin, and its expression is up-regulated upon activation of B cells. The expression of B7 and CD39 molecules on the surface of activated B cells appeared to be crucial since antibodies to these structures could block the induction of proliferation of the V delta 1+ T cells. Finally, we investigated the diversity of the responding V delta 1+ gamma delta T cell clones by sequence analysis of the TcR delta junctional regions. No restricted V-D-J sequences were found among the LCL-responsive V delta 1+ T cell clones, arguing strongly against a mono- or oligoclonal V delta 1+ gamma delta T cell response to LCL. These findings may explain the presence of polyclonally activated V delta 1+ T cells in inflamed tissues where activated B cells are often present.

Adenosine Triphosphatases