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Molecular dimensions of the substrate binding site of cytochrome P-448.

The molecular geometries of specific substrates, inhibitors and inducers of cytochrome P-448 activity were determined using computer-graphic techniques for use in defining the molecular dimensions of the substrate binding site of this enzyme. Specific substrates of cytochrome P-448 are essentially planar molecules characterised by a small depth and a large area/depth ratio. In contrast, compounds that do not serve as substrates of cytochrome P-448 are bulky, non-planar molecules characterised by small area/depth ratios and greater flexibility in molecular conformation. Specific inhibitors of cytochrome P-448 whose effect is mediated through interaction with the haem still meet the dimensional criteria for substrates indicating that they must also interact with the substrate binding-site, which is probably located in proximity to the haem. Inducers of cytochrome P-448 activity exhibit similar molecular geometries to the substrates from which it may be inferred that the cytosolic receptor associated with the induction of cytochrome P-448 activity is structurally related to the active site of the cytochrome.

Animals↗

Dummy measurement of chest injuries induced by two-point shoulder belts.

The University of Miami's William Lehman Injury Research Center at the Jackson Memorial Medical Center conducts interdisciplinary investigations to study seriously injured restrained occupants in frontal automobile collisions. Engineering analysis of these crashes is conducted in conjunction with the National Crash Analysis Center at the George Washington University. The multidisciplinary research team includes expertise in crash investigation, crash reconstruction, computer graphics, biomechanics of injuries, crash data analysis, trauma care, and all of the medical specialties associated with the Ryder Trauma Center at Jackson Memorial Hospital. More than 350 injured occupants and their crashes have been studied in depth. The purpose of this paper is to report on an observed pattern of liver lacerations suffered by drivers wearing shoulder belts, without the lap belt fastened and to assess the ability of existing crash test dummies to measure the potential for these injuries. During the initial years of the study, 48 cases of drivers protected by shoulder belts but without the lap belt fastened met the criteria for the study. Fifty percent of these drivers suffered liver lacerations. Further study showed that 22 of the crashes involved damage to the right front of the vehicle. Among the drivers in vehicles with right front damage, 92% sustained injuries to the liver. This observation indicated that 2-point belts were most likely to produce liver injuries in low severity frontal collisions when the crash direction is 1 to 2 o'clock. An analysis of the National Accident Sampling System for the years 1988-95 indicated that liver injuries constitute about 0.5% of the injuries suffered by drivers who are in tow-away crashes. NASS data showed that the risk of chest injury is more likely among drivers with automatic shoulder belts than drivers with 3-point manual belts. The crash test dummies showed no difference in chest injury measures. Finite element computer modeling demonstrated that the high deflection of the right lower rib on the Hybrid III dummy predicts the liver injuries in the 1 o'clock crashes. These higher deflections were less apparent at the location of the center chest deflection measurement device on the Hybrid III.

Accidents, Traffic↗

Three-dimensional reconstruction of the myofiber pattern in the fetal and neonatal mouse heart.

A methodology for three-dimensional reconstruction from serial sections and interactive computer graphics is described briefly. This methodology was applied to study the morphogenesis of the cardiac myofiber pattern in the fetal and neonatal mouse heart (ventricles). Few organized in-plane myofibers were found in the myocardial wall before 12 days postconception, but many fibers were observed in the very numerous trabeculae at all times up to birth. However, beginning at about 12 days, the number of fibers in the myocardial wall increases rapidly: these are seen predominantly in the transverse plane. The neonatal mouse heart, especially the left ventricle, resembles a small adult muscular artery. But the global myofiber pattern in the mouse heart at these stages appears to be more complex than might be inferred from earlier studies of the local myofiber pattern at a few sites in the ventricles of a few species of adult mammals. In particular, the pattern in and adjacent to the interventricular septum appears quite complex.

Animals↗

Using virtual reality technology for aircraft visual inspection training: presence and comparison studies.

The aircraft maintenance industry is a complex system consisting of several interrelated human and machine components. Recognizing this, the Federal Aviation Administration (FAA) has pursued human factors related research. In the maintenance arena the research has focused on the aircraft inspection process and the aircraft inspector. Training has been identified as the primary intervention strategy to improve the quality and reliability of aircraft inspection. If training is to be successful, it is critical that we provide aircraft inspectors with appropriate training tools and environment. In response to this need, the paper outlines the development of a virtual reality (VR) system for aircraft inspection training. VR has generated much excitement but little formal proof that it is useful. However, since VR interfaces are difficult and expensive to build, the computer graphics community needs to be able to predict which applications will benefit from VR. To address this important issue, this research measured the degree of immersion and presence felt by subjects in a virtual environment simulator. Specifically, it conducted two controlled studies using the VR system developed for visual inspection task of an aft-cargo bay at the VR Lab of Clemson University. Beyond assembling the visual inspection virtual environment, a significant goal of this project was to explore subjective presence as it affects task performance. The results of this study indicated that the system scored high on the issues related to the degree of presence felt by the subjects. As a next logical step, this study, then, compared VR to an existing PC-based aircraft inspection simulator. The results showed that the VR system was better and preferred over the PC-based training tool.

Adult↗

A method for quantitative image assessment based on redundant feature measurements and statistical reasoning.

Advances in computer graphics and electronics have contributed significantly to the increased utilization of digital imaging throughout the scientific community. Recently, as the volume of data being gathered for biomedical applications has begun to approach the human capacity for processing, emphasis has been placed on developing an automated approach to assist health scientists in assessing images. Methods that are currently used for analysis often lack sufficient sensitivity for discriminating among elements that exhibit subtle differences in feature measurements. In addition, most approaches are highly interactive. This paper presents an automated approach to segmentation and object recognition in which the spectral and spatial content of images is statistically exploited. Using this approach to assess noisy images resulted in correct classification of more than 97% of the pixels evaluated during segmentation and in recognition of geometric shapes irrespective of variations in size, orientation, and translation. The software was subsequently used to evaluate digitized stained blood smears.

Algorithms↗

The serous demilune of rat sublingual gland is an artificial structure produced by conventional fixation.

The ultrastructure of the secretory end-piece of the rat sublingual gland was examined in samples prepared by rapid freezing and freeze-substitution method, and results were analyzed in combination with 3-D images reconstructed by computer graphics from light micrographs of serial sections. Fixation by rapid freezing followed by freeze-substitution preserved cellular ultrastructures, especially the membrane structure, in perfect condition, and demonstrated the terminal portion of the sublingual gland to be a compound branched tubulo-alveolar gland with serous cells distributed throughout the end-pieces. All the serous cells aligned with mucous cells to surround a common lumen, leaving no demilune structure. In contrast, samples fixed by the conventional immersion method showed distended mucous cells displacing the serous cells toward the basal portion of the acinus to form the demilune structure. The luminal space was also compressed and appeared disconnected from the serous cells. From these observations, the serous demilune that for more than 130 years has been believed to be an actual histological entity was proved to be an artificial structure produced through compression by the hydrated and expanded mucous cells during immersion fixation.

5'-Nucleotidase↗

Volume rendering of tendon-bone relationships using unenhanced CT.

OBJECTIVE: Clinically, three-dimensional CT of the extremities is most often used to display bony anatomy. However, by combining unenhanced CT with volume-rendering computer graphics, visualization of relationships between bone and soft-tissue structures such as muscle tendon is also possible. The aims of this study were to quantify CT attenuation values of peripheral tendon, muscle, and bone on unenhanced CT and to develop custom opacity transforms on the basis of the attenuation measurements to effectively depict tendon-muscle-bone relationships. CONCLUSION: The mean attenuation of peripheral tendon ( approximately 100 H) is distinctly higher than that of muscle ( approximately 60 H) enabling high-quality volume rendering of muscle-tendon-bone relationships with unenhanced CT. High-frequency (bone) CT reconstruction algorithms commonly used for extremity CT produce approximately twofold higher image noise and inferior three-dimensional renderings compared with those based on less noisy standard or soft-tissue reconstruction algorithms. These concepts can be used to uniquely reveal tendon-muscle-bone relationships for clinical, scientific, and educational purposes.

Adult↗

Three-dimensional reconstruction from serial sections. V. Calibration of dimensional changes incurred during tissue preparation and data processing.

Three-dimensional (3-D) reconstructions from serial tissue sections produce a table of x, y, z coordinates (i.e., a numerical description of the object) that will support 3-D computer graphics displays and morphometric analyses. While measures such as volume or surface area can be generated interactively, almost instantaneously, they are usually of unknown accuracy due to artifacts that may be introduced at two different stages: (1) tissue shrinkage during dehydration and polymerization of a plastic and compression or expansion during sectioning and mounting and (2) geometric and intensity distortions during image capture and data processing. This paper describes simple methods for (1) introducing fiducials (reference marks) that allow measurement of the net distortion incurred during tissue preparation and (2) estimating the amount of geometric distortion arising during image capture and data processing. Application of these methods showed that the net areal change introduced in dog and sheep hearts during tissue processing amounted to +/- 5%. Apparently, the substantial shrinkage that occurs during tissue processing is largely compensated for by the expansion during tissue sectioning and mounting. The methods described may have application to other semisolid tissues.

Animals↗

Structural analysis of hepatitis B surface antigen by monoclonal antibodies.

A method has been developed for the analysis of hepatitis B surface antigen (HBsAg) antigenic structure at the molecular level that creates "fingerprints" or "signatures" of various hepatitis B viral (HBV) strains. This technique employs high affinity IgM and IgG monoclonal antibodies (anti-HBs) directed against distinct and separate determinants on HBsAg. In performing this antigenic structural analysis, separate binding curves for different monoclonal anti-HBs are generated by measuring immunoreactivity in serial dilutions of HBsAg-positive serum by radioimmunoassay. Since the HBsAg concentration in serum is unknown, the binding profiles of groups of samples are aligned by an iterative least-squares procedure to generate the numerical signature characteristic of the viral strain. The numerical signatures are then displayed on a computer-graphic plot. The signature profiles of HBsAg subtypes are a true reflection of their antigenic structure, and in vertical and horizontal transmission studies the molecular characteristics of the viral epitopes are conserved. By signature analysis we found substantial antigenic heterogeneity among the ayw3 strain both in the U.S. and France, as well as in populations of the Far East and Africa. Populations in Ethiopia, Gambia, and the Philippines were infected with two antigenically distinct HBV strains. In some newly identified HBV strains, it was found that epitopes identified by some monoclonal antibodies were absent or substantially reduced, which suggested that a genetic mutation may have occurred. Thus this study suggests that there is far more antigenic heterogeneity in HBV than previously recognized. These variants are antigenically distinct from each other at the epitope level, and were heretofore unrecognized by polyvalent anti-HBsAg antibodies.

Adult↗

A study of the veil cells around normal, diabetic, and aged cutaneous microvessels.

The veil cells around normal, diabetic, and aged vessels were reconstructed in 3 dimensions by a computer graphics system from 120-140 serial ultrathin sections. The normal vessel was surrounded by a single layer of veil cells which had a wrinkled and pleated surface. The diabetic vessels were surrounded by 3-6 layers of cellular material produced by increased numbers of veil cells and their associated cytoplasmic sheets. The veil cells around aged vessels appeared to have the same length as young and diabetic veil cells but were underdeveloped in their lateral extensions so that they did not cover the vessel circumferentially as well as did the normal veil cells. Preliminary data suggest that young, diabetic, and aged veil cells have the same metabolic activity per unit area of cytoplasm and are of the same length. The abnormal thickness or thinness of the vascular wall of dermal microvessels appears to be related to the degree of development and numbers of veil cells around the vessels rather than any change in their basic metabolic activity from normal.

Adult↗

Perinidal dilated capillary networks in cerebral arteriovenous malformations.

OBJECTIVE: The perinidal vascular structures of cerebral arteriovenous malformations were examined, to clarify their pathomorphological features. METHODS: Twenty-two resected specimens of human brain structures adjacent to the nidus were examined. The vessels surrounding the nidus were three-dimensionally reconstructed with a computer graphics system. RESULTS: In all cases, the analysis of serial sections revealed that perinidal dilated capillaries were located in brain tissue 1 to 7 mm from the nidal border. The vessels surrounding the nidus demonstrated markedly dilated capillary networks (perinidal dilated capillary network [PDCN]). The diameters of the vessels forming the PDCN were 10 to 25 times those of normal capillaries. The PDCN connected not only to the nidus, feeding arteries, and draining veins, via arterioles and venules, but also to the normal capillary network, arterioles, and venules. CONCLUSION: Without exception, each nidus was accompanied by a PDCN, which connected not only to the nidus, feeding arteries, and draining veins, via arterioles and venules, but also to normal capillaries, arterioles, and venules. The PDCN should be considered in studies aimed at gaining an understanding of the mechanisms underlying the intraoperative and postoperative bleeding, growth, and recurrence of surgically treated cerebral arteriovenous malformations.

Adolescent↗

The conformation of insulin-like growth factors: relationships with insulins.

The insulin-like growth factors and hystricomorph insulins have been modelled by interactive computer graphics on the assumption that their sequence homology to insulin implies that they will have a similar tertiary structure. These studies suggest that, although the insulin-related molecules can adopt the insulin fold, they are unlikely to form hexamers and if they form dimers they will be of reduced stability. The non-suppressibility of insulin-like growth factors by anti-insulin antibodies is explained in terms of differences of surface residues in the region A8-A10 and B1-B5. Receptor affinity of insulins and insulin-like growth factors for insulin receptors is explicable in terms of a receptor-binding site in the vicinity of B25 Phe on the insulin surface. An equivalent region around B25 Tyr of insulin-like growth factors may be responsible for their binding to type 1 receptors, although binding type 2 receptors must involve a different surface region not shared by insulin.

Amino Acid Sequence↗

A new fiducial alignment system to overlay abdominal computed tomography or magnetic resonance anatomical images with radiolabeled antibody single-photon emission computed tomographic scans.

BACKGROUND: The use of computed tomography (CT) or magnetic resonance (MR) to overlay or register uptake patterns displayed by single-photon emission computed tomography (SPECT) with specific underlying anatomy has the potential to improve image interpretation and decrease diagnostic reading errors. The authors have developed a method that will allow the selection of a region of interest on MR or CT images that correlates with SPECT antibody images from the same patient. This method was validated first in phantom studies and subsequently was used on three patients with suspected colorectal carcinoma. METHODS: Two patients were injected with the technetium-99m-labeled 88BV59 immunoglobulin G human antibody, and the third patient was injected with the iodine-131-labeled 16.88 immunoglobulin M human antibody. CT or MR scans were obtained before antibody infusion, and subsequent SPECT scans were obtained on the first or fourth day after infusion. A customized body cast with landmarks was used for each patient during the CT, MR, and SPECT scans to match slice positions for all scanning modalities. Corresponding fiducial landmarks were identified on axial images. A computer graphics program was written to match and overlay corresponding landmarks for each imaging modality. The image registration accuracy was measured by comparing fiducial marker separations (center to center) on the registered scans. This separation uncertainty was 1-2 mm for CT-MR and 3-4 mm for CT-SPECT phantom studies. RESULTS: For patient studies, the fiducial alignment uncertainty was 3-4 mm for axial CT-SPECT and MR-SPECT images, and 6-8 mm for sagittal CT-SPECT and MR-SPECT images. The accuracy of the anatomic alignment of the patient and image registration system was +/- 1 cm in the medial-lateral axis and +/- 2 cm in the cranial-caudal direction. CONCLUSIONS: This type of image analysis may resolve uncertainties with the anatomic correlation of SPECT images that otherwise may be regarded as questionable when SPECT is used alone for radioimmunodiagnosis.

Colorectal Neoplasms↗

Efficacy of a navigation system in neuro-endoscopic surgery.

OBJECTIVE: Neuro-endoscopy is playing a greater role in the diagnosis and treatment of several types of lesions, especially in the ventricular system. However, surgical planning and intraoperative orientation during endoscopic surgery are sometimes difficult. The efficacy of a neurosurgical navigation system using three-dimensional computer graphics of magnetic resonance (MR) images in neuro-endoscopic surgery was evaluated in this study. METHODS: We have developed a navigational endoscopic system designed to monitor the tip and direction of the endoscope, with the mirror marker of the navigation connected to a rigid endoscope. Eight patients, 3 cases of aqueductal stenting for isolated fourth ventricle, 3 cases of cystostomy for ependymal cyst, 1 case of septostomy for isolated lateral ventricle, and 1 case of ventricular tap in narrow ventricles, underwent endoscopic surgery using the present system. RESULTS: All patients underwent successful procedures with good outcomes. The present system was very useful in the cases of an accurate ventricular tap in narrow ventricles, identification of anatomic structures, and determining the appropriate route to the target point. CONCLUSIONS: This navigational endoscopic system improved the safety and accuracy of neuro-endoscopic surgery.

Adolescent↗

Cricoid area of the larynx: its physiological and pathological significance.

The three-dimensional distribution of the cricoid area was investigated using computer graphics and its histological structure and pathology were studied using whole-organ serial sections. A total of 26 adult human larynges were examined. The findings were as follows: 1. Cricoid areas were located along the superior portion of the cricoid arch on both sides. 2. The cricoid area was surrounded by the perichondrium of the cricoid cartilage, the conus elasticus and the fibrous layer of the subglottic mucosa. 3. The cricoid area was a loose areolar area, mainly composed of adipose tissue and loose elastic and collagenous fibers. 4. Many vessels were present in the cricoid area and a superficial branch of the cricothyroid artery ran through it. 5. Vessels in the cricoid area penetrated the anteroinferior portion of the conus elasticus and extended into the prelaryngeal region. 6. In larynges with laryngeal carcinoma, cancer invasion into the cricoid area and intravascular tumor invasion facilitated metastasis to the prelaryngeal, pretracheal and/or paratracheal regions and stomal recurrence. Cricoid areas were related to the growth pattern of laryngeal cancer.

Connective Tissue↗

A quality-control procedure on cervical lesions for the comparison of cytology and histology.

A new method for the quality control of cytologic and histologic diagnoses of cervical lesions is based on the automated high-resolution scanning, image processing and computer analysis of cytometric data by the TICAS system. It determines and then compares optical-density-based ploidy patterns of cells in cytologic smears and the corresponding histologic sections, with the results available both as computer-graphic displays and printouts. Examples of the former appear for an "agreement case," in which the cytologic and histologic patterns corresponded, and a noncorrespondence (nonrepresentative) case, in which the tissue sample had been nonrepresentative of the lesion sampled by cytology. Computergraphic examples concern one case of condyloma and one of tissue repair, in both of which both the cytologic and histologic diagnoses had been overcalled. A further example shows the method's use in monitoring response to therapy. The DNA ploidy patterns on which this method is based can give diagnostic and prognostic clues when morphology alone may be equivocal or insufficient. The utility of ploidy pattern determinations of material from other body sites is also well established. With the use of microprocessors, the system described could be made inexpensive and operationally simple for the routine quality control of many cytopathologic studies as well as for the clinical follow-up of patients.

Adult↗

Accurate three-dimensional reconstruction of neuronal distributions in brain: reconstruction of the rat nucleus locus coeruleus.

A technique is described which permits construction of accurate, quantified 3-dimensional maps of the distribution of neuronal cell groups in brain. The cartesian coordinates of landmarks and individual neurons are obtained from serial histological sections utilizing a computer-linked digitizing microscope. The digitized images of these sections are displayed on a computer graphics picture system where they are aligned so that spatial relationships within the nucleus are essentially identical to those of the intact brain. This is accomplished using information about landmarks obtained from photomicrotomy. As a consequence of the alignment procedure, each neuron is assigned a 3-dimensional coordinate representing its position in the reconstituted nucleus, and the reconstruction is oriented in a stereotaxic coordinate system. Nuclei from different brains can then be registered to one another, assigned coordinates relative to this standard coordinate space, and be compared statistically. Differences between nuclei in the spatial distribution of neurons in toto, or in the distribution of anatomically or physiologically defined subpopulations of neurons, can then be visualized with greater accuracy and in more detail than that permitted by traditional techniques. In addition, such comparisons can easily be quantified and statistically evaluated using, for example, analysis-of-variance techniques. For illustrative purposes, the technique is applied to the rat nucleus locus coeruleus as reconstructed from serial Nissl-stained sections.

Animals↗

Rat somatosensory cerebropontocerebellar pathways: spatial relationships of the somatotopic map of the primary somatosensory cortex are preserved in a three-dimensional clustered pontine map.

In the primary somatosensory cortex (SI), the body surface is mapped in a relatively continuous fashion, with adjacent body regions represented in adjacent cortical domains. In contrast, somatosensory maps found in regions of the cerebellar hemispheres, which are influenced by the SI through a monosynaptic link in the pontine nuclei, are discontinuous ("fractured") in organization. To elucidate this map transformation, the authors studied the organization of the first link in the SI-cerebellar pathway, the SI-pontine projection. After injecting anterograde axonal tracers into electrophysiologically defined parts of the SI, three-dimensional reconstruction and computer-graphic visualization techniques were used to analyze the spatial distribution of labeled fibers. Several target regions in the pontine nuclei were identified for each major body representation. The labeled axons formed sharply delineated clusters that were distributed in an inside-out, shell-like fashion. Upper lip and other perioral representations were located in a central core, whereas extremity and trunk representations were found more externally. The multiple clusters suggest that the pontine nuclei contain several representations of the SI map. Within each representation, the spatial relationships of the SI map are largely preserved. This corticopontine projection pattern is compatible with recently proposed principles for the establishment of subcortical topographic patterns during development. The largely preserved spatial relationships in the pontine somatotopic map also suggest that the transformation from an organized topography in SI to a fractured map in the cerebellum takes place primarily in the mossy fiber pontocerebellar projection.

Animals↗