Arthrodesis of the wrist in rheumatoid arthritis. A technique without external fixation.
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Adult↗
Biomedical subjects
M Malmsten
Publications and source records attributed to M Malmsten.
Cellular vaccines.
This project is devoted to the development of novel cellular vaccines designed to treat cancer patients. These cellular vaccines present and enhance immunogens, which will elicit a potent immune response. The goal is to achieve safe and effective immune reaction against the patient's own tumour. (1) Autologous cellular vaccines are prepared by processing circulating blood mononuclear cells outside of the patient's body (ex vivo) to differentiate them into antigen-presenting cells (APCs). Monocyte-derived APCs (MD-APCs) are then grown in the presence of exogenous target antigens (tumour cell debris, or apoptotic bodies) to become fully mature APCs. (2) Functionality for antigen presentation to T cells of ex vivo MD-APCs is evaluated in vivo. (3) Cellular vaccines are tested in selected rodent animal models. Efficiency and immune response are monitored in pertinent experimental systems for cancer. Pharmacological data are generated for clinical investigation. Tolerance and biologic effects are documented in primates. (4) The first clinical trials on cancer patients are taking place in 1998 on melanoma and prostate cancer to validate the concept. Specialized cell processors with dedicated software and standardized controls are being developed and used for the preparation of cellular vaccines. (5) The evaluation of new non-viral vectors and the validation of new non-viral transfection methods of mononuclear cells with marker genes is in progress and will lead to the ex vivo transfection of genes coding for immunostimulating cytokines or for tumour antigens in MD-APCs. Efficiency will be validated in vitro and in animal models. The ex vivo and animal model studies validate the clinical relevance of this new cellular immunotechnology. Clinical validation of individual autologous cellular vaccines in specific indications for which no treatment is presently available will allow the development of cellular and gene immunotherapy for other types of cancers.
Animals↗
Vascular smooth muscle, a multiply feedback-coupled system of high versatility, modulation and cell-signaling variability.
Under normal conditions, the various vascular regulatory effector influences are interwoven in a dynamic, and not a static, circulatory system. The reaction of a smooth muscle cell is thus reflected only incompletely by the stationary activation curve 'developed tension versus membrane potential'. The missing time domain in this relationship is a reflection of our as yet limited understanding of the system's behavior in space and time. It should be emphasized that the rhythmogenic properties of vascular smooth muscle are closely coupled to a functioning circulation. The electrical and mechanical oscillations, which can be traced back to rhythmic activity of the active, electrogenic Na+/K+ pump, could originate in the allosteric qualities of the enzyme phosphofructokinase (PFK). Thus, PFK represents a rhythmogenic enzyme which may serve as an example of the connection between the biological properties on a molecular level and the spatiotemporal system's behavior. The cardiovascular system and its rhythmicity may be dominated by only a few control points, one of which is distinguished by the viscoelastic properties of a blood flow sensor macromolecule. Therefore, the three prominent control points - PFK, (Na+ + K+)-ATPase and flow sensor conformation - acting as negatively feedback-coupled, nonlinear synergetic order parameters, are sufficient to initiate the periodic events in the cardiovascular system and to provide a plausible explanation for their causal origin.
Adenosine Triphosphate↗