The formation of complexes involving more than two proteins is critical for many cellular processes, including signal transduction, transcriptional control, and cytoskeleton remodeling. ...Energetically, these interactions cannot always be described simply by the additive effects of the individual binary reactions that make up the overall complex. This is due, in large part, to cooperative interactions between separate protein domains. Thus, a full understanding of multiprotein complexes requires the quantitative analysis of cooperativity. We have used surface plasmon resonance techniques and mathematical modeling to describe the energetics of cooperativity in a trimolecular protein complex. As a model system for quantifying cooperativity, we studied the ternary complex formed by the simultaneous interaction of a superantigen with major histocompatibility complex and T cell receptor, for which a structural model is available. This system exhibits positive and negative cooperativity, as well as augmentation of the temperature dependence of binding kinetics upon the cooperative interaction of individual protein components in the complex. Our experimental and theoretical analysis may be applicable to other systems involving cooperativity.
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IJS, KILJ, NUK, PNG, UL, UM
Purpose:
Surgical treatment of extensive orbital tumors sometimes is challenging concerning the preoperative planning, surgical approaches, and simultaneous plastic reconstruction in cases of complex ...defects. Therefore an algorithm regarding multimodal and interdisciplinary concepts had to be established.
Method:
We report a series of 75 cases with tumors (64% malign, 36% benign) infiltrating the orbit and periorbit, requiring a subtle preoperative diagnostic interpretation. In some cases it was necessary to formulate a complex treatment plan with transfer of the plan by use of image-guided techniques, the choice of individualized surgical approaches, and plastic surgical reconstruction regarding the functional as well as aesthetic requirements. In all cases the extension of the tumor could be visualized by use of tomographic modalities, in some special cases with fusion of the image data for segmentation of the tumor volume. For tumor resection, transorbital approaches (28%), in cases with infiltration of the anterior skull base in combination with coronal incisions (27%) and craniotomy (24%), allowed for a good visualization of the tumor and protection of the neighboring structures. For the reconstruction of the anterior skull base, calvarial bone grafts, in special cases in combination with free flaps from the radial forearm or the subscapular system, were necessary. Those were often combined with simultaneous insertion of craniofacial implants which served for later epithetic reconstruction of the orbital region.
Result:
Tumor resection with clear margins was possible in most of the cases (95%), therefore showing in cases of malignancies a good overall survival rate. Due to the use of diagnostic modalities with good discrimination of the tumor's extent, we were able to choose individualized strategies with implementation of preoperative planning techniques found to be useful also in the choice of surgical approach as well as for the simultaneous reconstruction in case of complex bony defects. The follow-up showed good oncologic as well as functional and aesthetic treatment results.
Conclusion:
Orbital tumors present like a kaleidoscope of very different pathological entities requiring individualized therapeutic strategies with the use of multimodal techniques being used by an interdisciplinary team. Furthermore, a broad portfolio of reconstructive techniques is necessary to guarantee a good functional and aesthetic long-term result.
