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Early mineral deposition in calcifying tendon characterized by high voltage electron microscopy and three-dimensional graphic imaging.

Extracellular matrix organization and the spatial relationship between collagen fibrils, vesicular structures, and the first deposits of mineral in the calcifying leg tendon from the domestic turkey, Meleagris gallopavo, have been investigated by high voltage electron microscopy and three-dimensional computer graphic imaging of serial thick tissue sections. The work demonstrates that the tendon extracellular matrix is a complex assembly of somewhat flexible, highly aligned collagen fibrils with different diameters and occasionally opposite directionality. Smaller collagen fibrils appear to branch from larger fibrils or to aggregate to form those of greater size. While the matrices are dominated by fibrils, space exists between adjacent packed fibrils. The three-dimensional perspective indicates that approximately 60% of the total tendon volume is extrafibrillar over the regions examined. The first observable mineral in this tissue is extrafibrillar and appears to derive from vesicles. This view of three-dimensional matrix-mineral spatial relations supports earlier two-dimensional results that mineral is initially associated with membrane-invested vesicles and is deposited between collagen fibrils, but it is distinct in showing the mineral at different depths in the matrix rather than at a single depth as deduced from two-dimensional conventional electron microscopy. These results are important in the onset and development of tendon calcification in that they suggest, first, that collagen fibrils appear to be aligned three-dimensionally such that their hole zones are in contiguous arrangement. This situation may create channels or grooves within the collagen volume to accommodate extensive mineral deposition in association with the fibrils. Second, the results indicate that there are widely dispersed sites of vesicle-mediated mineralization in the tendon matrix, that the bulk of mineralization in this tissue is collagen-mediated, and that, while vesicles may possibly exert some local influence temporally on mineralization of neighboring collagen, vesicle- and collagen-mediated mineralization arise at spatially and structurally distinct sites by independent nucleation phenomena. Such concepts are fundamental in considerations of possible mechanisms of mineralization of tendon and potentially of other normally calcifying vertebrate tissues in general.

Animals

Three computer methods to reconstruct pulpal blood vessels and nerves.

This study describes three methods of computerized three-dimensional reconstruction of the main neurovascular pulpal bundle of human teeth, using serial cross-paraffin sections, digital image processing, and three-dimensional computer graphics. These methods are surface representation, representation by means of a stack of slices, and volume representation.

Adolescent

Active site model of cytochrome P-450 LM2.

Based on (i) a detailed analysis of the physicochemical properties of selected benzphetamine derived substrates and (ii) the identification of Tyr-380 as active site residue trans to thiolate theoretical studies (computer aided molecular design) revealed a model of the substrate binding site of cytochrome P-450 LM2. The results indicate that substrates with a butterfly-like bulky conformation exhibit the highest intrinsic activity. Those substrates which preferably exist in an extended conformation are sterically hindered to intensively interact with the binding site which is demonstrated by computer graphics.

Benzphetamine

Three-dimensional display of the pelvic structure of anorectal malformations based on CT and MR images.

Three-dimensional images of the pelvic structure of patients with anorectal malformation (ARM) were constructed by computer graphics based on radiographic computerized tomography (CT) and magnetic resonance (MR) images. Organ contour data from CT images and raw MR image data were transferred to a personal computer and to a graphic workstation respectively. On MR image processing, organs were extracted semiautomatically by thresholding enclosed areas. After several steps of image processing, three-dimensional anatomy of each anomaly was visualized with emphasis on position and shape of the muscle complex. In control patients without an anomaly, images showed that the rectum is supported by the levator muscle from behind and descends along with the urethra. In the male patient, the anal canal separates from the urethra and penetrates through the middle of the sphincter complex to reach the orifice. In those with low-type anomaly with a fistula opening to the perineum or the vestibule, images showed the fistula descending through the anterior portion of the sphincter complex. Images of those with a rectourethral fistula could show the muscle complex behind the rectum and at the region where the external sphincter should be. In those with cloacal anomalies, anatomical position and the shape of three different viscera were easily recognized, and the muscle complex was shown like that of rectourethral-type anomalies. This study is a new approach to the anomaly to facilitate understanding it and can assist a surgeon in planning a procedure. This kind of application would make it possible for a surgeon to consider the strategy on a display screen before the real surgery.

Anal Canal

Three-dimensional digitization: method for evaluating morphological differences between teeth.

A new comparative method has been developed for evaluating morphological differences between a pair of teeth. This method consists of five steps: 1) digitization of the surface morphology of the teeth, 2) standardization to enable comparison of the teeth on a common axis, 3) reversal of data on one tooth to enable comparison with the opposite tooth, 4) qualitative evaluation by computer graphic superimposition and 5) quantitative evaluation by the set operation. To illustrate its effectiveness, this method was applied to a pair of extracted premolars. Application to the dental crown on a clinical plaster cast was also discussed.

Bicuspid

A new anatomical representation of the human visual pathways.

A three-dimensional, computer-aided reconstruction of the intracranial parts of the visual system, optic nerve, optic chiasm, optic tract, lateral geniculate body, optic radiation and striate area on the basis of anatomical serial cuts is presented in this paper. The computer-graphic representation simulates the illumination of a three-dimensional reconstruction. This study depicts for the first time a detailed anatomical reconstruction and illustrative representation of the striate area. An interactive investigation of the structure on the screen as well as a demonstration of the intracranial relationships between different neuroanatomical structures and comparisons with magnetic resonance, computed tomographic, and positron emission tomographic images is possible, providing that the neuroimaging uses the identical Cartesian coordinate system [22].

Aged

[Stereology of the dermo-epithelial interface of the matrix-papilla unit of the hair bulb. Computerized processing of tridimensional images].

Images of the spatial relations of the matrix-papilla unit of the human hair bulb are shown. Hair bulbs were reconstructed in 3 dimensions by a computer graphics system from measurements made on horizontal sections parallel to the scalp surface. The outlines of hair matrix and dermal papilla of every fifth serial sections were fed into a computer as a segment 30 mu high (5 sections, each 6 mu thick). Processing of these segments into 3 dimensional models, using techniques adapted from those currently used for architectural drawing enabled us to avoid major distortion of the printed pictures. As an end result, the hair bulbs appear as wire frame structures in which the boundaries between consecutive segments have been connected to improve rendering of the dermal papilla interacting with the overlying epithelial hair matrix. This computerized method has been used to evaluate dermal-epithelial stereology of the interacting dermal papilla and epithelial hair matrix in hair bulbs. In a patient with trichorhinophalangeal syndrome the hair bulbs, and especially their dermal papillae, were found to the hypotrophic as compared with a sex- and age-matched control. Even though the pictures are somewhat artifactual in their present form, there are several means of improving the rendering of relief and of the interrelation between the hair follicle and other surrounding structures. This method could be useful to demonstrate disturbed dermal-epithelial interactions in other types of alopecia and to evaluate potential biological effects of drugs used in the treatment of alopecia.

Computer Graphics

An algorithm for planning stereotactic brain implants.

A computer software package was developed for the planning and execution of brain biopsy and radioactive implant procedures with the BRW Stereotaxic System. With the application of computer graphics and a zero-one integer variable programming algorithm, an implant plan with accompanying isodose distributions and stereotactic coordinates can be easily accomplished at the time of the operation when the computer imaging terminal and a printer/plotter is placed in the operating room.

Algorithms

The personalized hip prosthesis.

The authors discuss the general concept, method of use and first clinical results obtained with a "personalized" femoral component of a hip arthroprosthesis based on the computer-graphic processing of measurements obtained from radiography and CT scan. This prosthesis is considered to be innovative as compared to traditional cementless prostheses.

Computer Graphics

Computerized Arden grating technique for the measurement of the contrast sensitivity function.

We developed a computerized contrast sensitivity function (CSF) measurement technique using a computer graphics board to reproduce Arden grating type stimuli. The reliability of the procedure was examined by evaluating the standard deviation of repeated test differences. The validity of the procedure was tested by comparison with both a manual method of adjustment technique and with Regan low contrast letter charts. The procedure has been performed at a number of exposure speeds to account for the effect of reaction time and attention of the results. The optimum exposure time for the procedure has been found to be greater than or equal to 22 s. As a result of the benefits of automation the test is quick, produces test-retest correlation coefficients for the five spatial frequencies tested which are similar to those for the method of adjustment procedure (0.76 to 0.91 for the computerized test, 0.66 to 0.88 for the signal generator measurements), and produces values which correspond closely with the method of adjustment measurement. It has the advantages of utilizing hardware already available in many computer systems, having a constant mean luminance across the screen, and having a constant and optimized presentation time.

Adult

[Development of the method of ultrasound topometry of the thyroid gland and computer programs in the planning of radioactive iodine therapy].

The paper is concerned with the problem of stereological volumenometry applied to the problems of ultrasound topometry of the thyroid. The organ surfaces are tightened on the basis of information obtained from echotomographic films using a method of cubic spline-interpolation, parametric function setting and methods of computer graphics. Images of sections can be obtained with an arbitrary step and an angle of inclination to the organ longitudinal axis. The main sources of errors of the method were estimated, and their numeric values were given.

Algorithms

Extracting prototypical facial images from exemplars.

A computer graphic method for extracting a natural image of an individual's facial prototype, or average appearance, from a number of different images of that individual is presented. The process improves upon previous photographic and computational techniques. Synthesis of a person's average expression and pose from a sample of images is derived in an automatic and quantitative way. Possible uses of composite faces produced in this manner in psychological investigations of facial qualities (eg attractiveness) and in applied areas such as telecommunication are pointed out.

Attention

Computer-assisted restriction mapping: an integrated approach to handling experimental uncertainty.

Building a map of restriction sites from double-digest gel data can be a complex and frustrating task, especially when many DNA fragments are detected or when the gel results are ambiguous. 'Double Digester' is an interactive, graphical computer program which helps researchers understand and resolve such data. It explicitly represents the experimental data, the associated uncertainties, the researcher's hypotheses and possible map interpretations. Alternative solutions are frequently possible, and the differences between them may help determine which additional experiments might resolve ambiguities. Initial use has confirmed the benefits of this approach, and has suggested ways in which it can be refined and extended. Double Digester meets the need for a practical tool to help build restriction maps, and also illustrates how a computer-based tool can confront experimental uncertainty in an integrated fashion.

Algorithms

Image analysis and quantification of atherosclerosis using MRI.

This paper describes an image processing, pattern recognition, and computer graphics system for the noninvasive identification and evaluation of atherosclerosis using multidimensional Magnetic Resonance Imaging (MRI). Particular emphasis has been placed on the problem of developing a pattern recognition system for noninvasively identifying the different plaque classes involved in atherosclerosis using minimal a priori information. This pattern recognition technique involves an extension of the ISODATA clustering algorithm to include an information theoretic criterion (Consistent Akaike Information Criterion) to provide a measure of the fit of the cluster composition at a particular iteration to the actual data. A rapid 3-D display system is also described for the simultaneous display of multiple data classes resulting from the tissue identification process. This work demonstrates the feasibility of developing a "high information content" display which will aid in the diagnosis and analysis of the atherosclerotic disease process. Such capability will permit detailed and quantitative studies to assess the effectiveness of therapies, such as drug, exercise, and dietary regimens.

Algorithms

Medicinal chemistry: a support or a driving force in drug research?

The foregoing has demonstrated most emphatically the significant and central role which chemistry plays in modern and future drug research. It does not mean to diminish the important role of biology but it does serve to show that chemistry is not merely a support for the needs of biology but is a powerful driving force in itself. The two disciplines are essentially interdependent and each relies on the other for success in drug design, discovery and eventual delivery of a useful medicament to the patient. Finally, the medicinal chemist today is faced with as many if not more formidable challenges in medicinal research as his counterpart of a generation ago. The sciences of genetics, molecular biology, neuro-pharmacology and electrophysiology have expanded the knowledge base of cellular function many fold. This new knowledge when coupled with the fundamental role of biochemistry in outlining in chemical terms both normal and abnormal cellular events offers the researcher a much more sophisticated appreciation of the cause of disease states. Knowing which enzymes or receptors are involved is a crucial step towards correcting the malfunctioning cellular conditions. With powerful new methods for determining the three-dimensional structure of molecules and computer graphics which give insight on rational drug design and modification, the medicinal chemist can explore with greater confidence than ever before the road to new drugs. The new biology, the new physical methodology and the computer have enhanced the role of chemistry in modern drug research and have given the medicinal chemist a more profound grasp of cellular aberrations leading to disease. This knowledge is a golden rod in the hands of an imaginative chemist in the search of innovative drugs.

Biochemical Phenomena

Fabrication of total-contact burn masks by use of human body topography and computer-aided design and manufacturing.

Total-contact burn masks are used to treat scar tissue hypertrophy of the face. The mask should conform very closely to the contours of the face and provide evenly distributed pressure. The mask is worn continually throughout wound maturation. Lack of fit because of an inability to obtain exact facial contours by use of an alginate material diminishes the effectiveness of the mask. A multidisciplinary team representing physical therapy, CAD/CAM (computer-aided design and computer-aided manufacturing), biomedical engineering, and prosthetics has advanced the method of developing total-contact burn masks by use of human body electronic imaging, computer graphics, and numerically controlled milling processes. High-resolution surface scanning and CAD/CAM have been used successfully to accurately fabricate three such masks. The methodology and preliminary results from use of these state-of-the-art techniques are described in this article.

Burns

A model for hormone receptor binding to the mouse mammary tumour virus regulatory element based on hydroxyl radical footprinting.

The mouse mammary tumour virus long terminal repeat region contains regulatory sequences able to mediate transcriptional induction by different steroid hormones. Two clusters of binding sites for the glucocorticoid and the progesterone receptors have been identified in the region between -70 and -190, the so called hormone responsive or regulatory element. To understand the molecular details of the interaction between the receptors and the DNA we have used the high resolution technique of hydroxyl radical footprinting. Both in the promoter distal site and in the promoter proximal cluster additional contacts between the proteins and the double helix are detected by this technique, outside of the region identified by methylation protection. The pattern of contacts in the promoter distal region is compatible with a model involving the interaction of a receptor dimer with the major grooves of four subsequent turns of the double helix, each turn being contacted by a separate zinc finger. This model is illustrated by computer graphical methods and discussed in terms of sequence homologies with other hormone regulatory elements.

Animals

Computer-generated slide graphics: an exciting advancement or a problem?

Computer-generated slide graphics have significantly altered the face of audiovisual presentations. However, it remains to be determined if dramatic effects enhance presentation clarity and increase information retrieval. This study compared color combination and print type graphics. Ninety medical students were shown a 29-minute, 45-slide presentation addressing aspects of plastic surgery. Each slide represented one of 15 color combinations and one of 3 fonts. The students studied each slide for 10 seconds and then in 25 seconds recorded all information they could recall. Statistical analysis (using ANOVA) revealed a significant difference in information retrieval among slides and a significant interaction between color and font. The "best" was orange block print on a raspberry background. The "worst" was yellow cursive print on a black background. This study demonstrated that (1) color influences information gleaned from a slide presentation and (2) font type simplicity may result in improved retention.

Audiovisual Aids