Allosteric activation of protein phosphatase 2C by D-chiro-inositol-galactosamine, a putative mediator mimetic of insulin action.

Insulin-stimulated glucose disposal in skeletal muscle proceeds predominantly through a nonoxidative pathway with glycogen synthase as a rate-limiting enzyme, yet the mechanisms for insulin activation of glycogen synthase are not understood despite years of investigation. Isolation of putative insulin second messengers from beef liver yielded a pseudo-disaccharide consisting of pinitol (3-O-methyl-d-chiro-inositol) beta-1,4 linked to galactosamine chelated with Mn(2+) (called INS2). Here we show that chemically synthesized INS2 has biological activity that significantly enhances insulin reduction of hyperglycemia in streptozotocin diabetic rats. We used computer modeling to dock INS2 onto the known three-dimensional crystal structure of protein phosphatase 2C (PP2C). Modeling and FlexX/CScore energy minimization predicted a unique favorable site on PP2C for INS2 in a surface cleft adjacent to the catalytic center. Binding of INS2 is predicted to involve formation of multiple H-bonds, including one with residue Asp163. Wild-type PP2C activity assayed with a phosphopeptide substrate was potently stimulated in a dose-dependent manner by INS2. In contrast, the D163A mutant of PP2C was not activated by INS2. The D163A mutant and wild-type PP2C in the absence of INS2 had the same Mn(2+)-dependent phosphatase activity with p-nitrophenyl phosphate as a substrate, showing that this mutation did not disrupt the catalytic site. We propose that INS2 allosterically activates PP2C, fulfilling the role of a putative mediator mimetic of insulin signaling to promote protein dephosphorylation and metabolic responses.

The contribution of imaging and digitised data to mandibular reconstruction and implant stabilised occlusal rehabilitation: a case report.

Different methods are recommended for the surgical reconstruction of the resected mandible. The advantages for implant stabilised prostheses in restoring the occlusion are recognised but few papers provide adequate data to identify the successful outcome of treatment. The literature is reviewed and the advantages of imaging together with the use of digitised data is highlighted by a case requiring rehabilitation with enhanced planning methods.

Three-dimensional visualization of data on human anatomy: diagnosis and surgical planning.

A system is described which produces displays of anatomical surfaces from sets of X-ray computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonographic scans (US). The displays are created to show the three-dimensional character of the internal and external anatomy. The images may be manipulated on the screen to simulate dissection of the three-dimensional object they represent. Thus it is possible to increase the diagnostic value of the original data and to plan surgery by simulation. To allow long-term studies on the human face for surgical planning and assessment a non-hazardous optical scanning system has been devised. The display system also produces data to drive a numerically controlled milling machine for the production of models, prostheses and implants.

Three-dimensional visualization of computerized tomography and laser scan data for the simulation of maxillo-facial surgery.

A system has been developed for the three-dimensional (3D) visualization of the face and skull using data obtained from a purpose-built no-contact laser scanning system and from a series of scans produced by X-ray computerized tomography. Features developed allow the simulation, planning and prediction of maxillo-facial surgery. Realistic skeletal and facial images with a solid 3D appearance are produced from these two datasets using computer graphics techniques. The images can be sectioned for diagnostic purposes or parts can be repositioned for the simulation of surgery. 3D measurements can be made on the images for pre- and post-surgical analysis. An example of the clinical use of the system in the planning of surgery and the prediction of post-surgical facial appearance is given.

Using greyscale voxel databases for improved shading and segmentation.

Many different data representations are possible in computer graphics. Originally, in the medical field, simplified methods were used in order to reduce computation times on small computer systems. Currently a wider range of techniques is developing as costs of hardware continue to fall. In this paper we review a number of possible representations and explain the advantage of one that is greyscale, volumetric and random access. Different segmentation techniques can be used, as well as shading algorithms that give greatly improved appearances. A quantitative analysis of shading methods is derived in terms of the degree of sampling of the 'pseudo-normal' vectors that estimate the direction of the tangent to a surface. The application to a study of multiple sclerosis lesions in the brain using nuclear magnetic resonance data is shown.

A computer system for the interactive planning and prediction of maxillofacial surgery.

A computer system has been developed for the simulation of facial surgery with interactive three-dimensional graphic techniques and data derived from computed tomographic scans and a purpose-built laser scanning system. The simulation includes the surgery on the hard tissues, and modeling of the soft tissue for prediction of the postoperative facial appearance. The facilities available are described and an example of their use is given.

Investigation of human skeletal muscle structure and composition by X-ray computerised tomography.

In muscular dystrophy and metabolic myopathy there is wasting and replacement of the muscle bulk with fat and fibrous tissue. A method for estimating the fat content of muscle and the cross-sectional area from computerised tomography (CT) scans is presented. Data from the quadriceps muscle of fifty patients show the effect of fat replacement on muscle strength. The CT scans have shown that the pattern of wasting in individual muscle groups is characteristic of the type of myopathy. In Duchenne muscular dystrophy, hypertrophic and pseudohypertrophic muscle have hitherto been indistinguishable, but this method allows a clear distinction to be made. Quantitative CT offers a new approach to the investigation of muscle diseases and can also be of considerable value in selecting sites for needle biopsy of muscle.