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Microtubules and their protofilaments in the flagellum of an insect spermatozoon.

Spermatozoa of stick insects have nine accessory tubules, which surround the nine outer microtubular doublets and the two inner microtubular singlets. When fixed in a fixative that was designed to minimize protein denaturation (glutaraldehyde and tannic acid, no osmium post-fixation but block staining with uranyl acetate in water) the accessory tubules were seen to contain 17 protofilaments of the same type as those in the 9 + 2 microtubular doublets and singlets. The protofilaments in accessory tubules and other microtubules were roughly triangular. When studied by Markham's photographic method a somewhat different tilt of the two longer sides was seen; this makes it possible to distinguish a polarity in the microtubules, i.e. to differentiate between a microtubule that is viewed from its (-)end to its (+)end from one that is viewed in the opposite direction. The dynein arms of the doublets can be used as an independent type of marker for the polarity. In a computer-aided analysis of the fine structure of the tail axoneme, the A-subtubules of the outer doublets were seen to be not quite equidistant; rather, there were somewhat widened electron-dense interspaces in the ring of protofilaments in four places. The locations of these widened interspaces coincide with the attachment sites for the spoke, the inner dynein arm, the outer dynein arm, and the intertubular material. It is tentatively concluded that proteins of these structures, and perhaps also other microtubule-associated proteins, may be anchored deep within the wall of a microtubule rather than just superficially along it.

Animals

[Computer-aided diagnosis of interstitial lung diseases].

We are developing an automated method for determination of quantitative physical measures of lung textures in digital chest radiographs in order to detect and characterize interstitial lung disease. We describe a scheme of our approach for lung texture analysis, an automated classification method for distinction between normal and abnormal lungs with interstitial disease, and the effect of digital parameters on the accuracy of this computerized analysis, as well as applications of this method to the ILO pneumoconioses standard radiographs. The root-mean-square (rms) variation and the first moment of the power spectrum of the lung texture were determined as quantitative texture measures based on a frequently analysis of lung textures, which represent the magnitude and coarseness (or fineness) of the lung textures, respectively. The computerized classification method is based on the analysis of these texture measures and on a data base derived from clinical cases. This classification method includes three independent tests, one for a definitely abnormal focal pattern, one for a relatively localized abnormal pattern, and one for a diffuse abnormal pattern. A comparison of receiver operating characteristic (ROC) curves obtained by radiologists and by means of the computerized classification method indicates that the computerized approach may provide performance similar to human observers in distinguishing lungs with mild interstitial disease from normal lungs. By investigating the effect of digital parameters such as pixel size, ROI size and the number of quantization levels on these texture measures obtained from the lung texture analysis and the performance of this computerized method, we attained a useful guide in the design of this computerized scheme. Texture measures obtained from computer analysis of the ILO pneumoconioses standard radiographs corresponded closely with the ILO classification categories for small opacities, though it was necessary for a qualified radiologist to identify representative areas in each ILO radiograph because of the inhomogeneous distribution of texture patterns in these standard radiographs. Our results suggest strongly that this computerized method can be a valuable aid to radiologists in their assessment of interstitial lung diseases.

Humans

Receptor-recycling model of clearance and distribution of insulin in the perfused mouse liver.

After perfusion of mouse livers with A14-125I-insulin for designated intervals, an acid-wash technique was employed to separately measure the surface-bound (Xs) and intracellular (Xi) A14-125I-insulin, as well as intracellular degradation products (Xdeg) of labelled insulin. From the perfusate concentrations (Cp) of A14-125I-insulin, the apparent intrinsic hepatic clearance of labelled insulin at a high dose (0.2 nmol/l) was shown to be 60% smaller than that at a low dose (0.018 nmol/l), indicating that the cellular uptake of insulin is remarkably nonlinear at the concentration range examined. From the time courses of Cp, Xs, Xi and Xdeg, the hepatic insulin disposition was shown to be largely accounted for by the receptor-mediated endocytosis. The observed data at the low dose were analysed to estimate biochemical parameters, (i.e., total receptor number, endocytotic rate constant and intracellular degradation rate constant) according to "receptor-recycling" and "non-receptor-recycling" models, using a computer-aided optimization procedure. The "receptor-recycling" model could not only adequately explain the Cp, Xs, Xi and Xdeg at the low dose, but also predict the Cp at the high dose. On the other hand, a "non-receptor-recycling" model, in which recycling of receptors was not assumed, could also explain the observed data at the low dose, but failed to predict the Cp at the high dose, indicating that the receptor recycling process is necessary to explain the hepatic insulin clearance at high insulin concentrations, at which hepatic insulin clearance should be limited by the rate of receptor recycling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Isoresponse time regions for the evaluation of visual search performance in ergonomic interface models.

Computer-aided ergonomic evaluation models often provide a limited function of visual performance, usually in the form of visibility tests at any given location. It is, however, of great importance to complete a visual task in a predetermined time successfully or to predict the time to complete the task, e.g., a task of high-level control such as aircraft flight operations. In this study, isoresponse time regions which have an effect on visual performance in real-life situations are presented as an effort to complement aforementioned shortcomings of ergonomic interface models. A multiple regression was used to provide equal response time regions, being asymmetrical in shape. In addition, the fuzzy linear regression (FLR) model was introduced to provide a fuzzy set from which a decision-maker might select appropriately. It provided similar fitted values with having the advantage of utilizing the interval of those fitted values over the conventional regression model. The results can be applied effectively to the design of an interface for diverse visual tasks in real situations.

Adult

Computer-assisted three-dimensional volumetry of the human pulmonary acini.

Computer-aided three-dimensional (3-D) volumetry of human pulmonary acini was undertaken using the left upper lobe of a 51-year-old female operated for small lung cancer. A normal part of this lobe, fixed by intrabronchial infusion with a mixture of polyethylene glycol and formalin, was subjected to serial sectioning, using a special slicer, into 48 serial slices of 0.5 mm in thickness. A soft x-ray radiograph was prepared from each slice at x 12, and the contours of airways and acinar boundaries contained in it were input by digitization into a microcomputer for 3-D reconstruction and volumetry. The estimated volumes of 130 acini were unexpectedly uniform, showing a normal type distribution with a mean of 172.7 +/- 37.9 mm3. No significant correlation proved to exist between the volume of acini and the number of branching generation of the terminal bronchioles (TBs) they received. Furthermore, there was no significant difference in volume among the acini facing the costal surface, those facing the mediastinal surface and those not facing any pleural surface. However, the generation number of TBs was shown to differ significantly with the location of acini. These results suggest that the tree of conductive airways is designed so as to meet the requirement of constant acinar volume.

Adenocarcinoma

Modeling and conformation analysis of beta-cyclodextrin complexes.

A series of beta-cyclodextrin complexes containing various guest molecules was studied using computer-aided molecular modeling and conformation analysis techniques. The geometry of each complex was studied using crystallographic data. The positions of the glycosidic O4 atoms indicate that the beta-cyclodextrin molecules are elliptically distorted. This distortion can be related to the van der Waals volume of the guest molecules. This correlation is different for aromatic and non-aromatic guest compounds. Rigid body docking experiments demonstrated that in crystal structures the guest molecule occupies a position in the cavity of nearly minimum interaction energy when there are no other molecules having interactions with the guest molecule. From the crystallographic data several rules could be deduced which seem to determine the conformation of beta-cyclodextrin molecules in complexes. A procedure was developed to construct beta-cyclodextrin molecules that are able to encompass guest molecules having a given van der Waals volume.

Carbohydrate Conformation

Computer-aided diagnosis of "dyspepsia".

Experience with computer-aided diagnosis of "dyspepsia" in a consecutive prospective series of 212 patients coming to surgery is described. Analysis is concentrated upon 122 patients who presented to an outpatient clinic de novo for diagnosis. During their first (outpatient) hospital contact, a firm diagnosis was made in just over half of these patients (though where made, it was usually correct). After full investigation, the diagnostic accuracy (prior to operation) was 92.6%. Using data elicited solely from the house surgeon's interview at the time of admission, the computer's overall diagnostic accuracy was 87.7%. The cost of each new computer diagnosis was around 25 new pence ($0.60). and the time taken was about 5 minutes. In a further small series designed to discriminate between organic and functional dyspepsia, the computer correctly assigned all but 1 of 23 patients with organic disease to the correct disease category. However, almost half of 33 patients with x-ray negative dyspepsia were predicted by the computer to have organic lesions. Time alone will tell whether the computer is a better early predictor of eventual organic disease than currently available radiologic methods.

Bayes Theorem

Construction of new ligand binding sites in proteins of known structure. I. Computer-aided modeling of sites with pre-defined geometry.

We have devised a molecular model building computer program (DEZYMER) which builds new ligand binding sites into a protein of known three-dimensional structure. It alters only the sequence and the side-chain structure of the protein, leaving the protein backbone fold intact by definition. The program searches for a constellation of backbone positions arranged such that if appropriate side-chains were placed there, they would bind the ligand according to a pre-defined geometry of interaction specified by the experimentalist. These binding sites are introduced by the program by taking into account simple rules such as steric hindrance, atomic close-packing and hydrogen bond patterns, which are known to maintain the integrity of a protein structure to a first approximation. A test case is presented in this paper where the copper binding site found in blue-copper proteins such as plastocyanin, azurin and cupredoxin is introduced into Escherichia coli thioredoxin. The model building of one of the solutions found by the program is presented in some detail. The experimental construction and properties of this new protein are described in an accompanying paper. It is hoped that this program provides a general method for the design of ligand binding sites and enzyme active sites, which can then be tested experimentally.

Algorithms

Comparison of computer-aided and human review of general practitioners' management of hypertension.

Computer programs that automatically review decisions can help physicians provide better patient care. In the Netherlands, the ELIAS computer information system has replaced paper medical records in some general practices. We have written a computer program called 'HyperCritic' that audits general practitioners' management of patients with essential hypertension by taking patient-specific data from the ELIAS system. We investigated whether the computer-based medical records contain sufficient information to generate critiques, and compared the limitations of audit by hypercritic with those of review by a panel of eight physicians. Hypercritic and the physicians independently reviewed the medical records of 20 randomly selected patients with hypertension and commented on the decisions made at each of 243 patient visits. Of 468 comments on patient management, 260 were judged correct by six or more of the physicians; hypercritic also made 118 of these 260 comments. The main reasons why the program did not produce the other 142 comments were: insufficient data in the computer-based medical record; absence of sufficient medical consensus; and omissions in the database of hypercritic. Calculation of an "index of merit" ([sensitivity + specificity] - 1) for individual reviewers showed that hypercritic performed better (index of merit 0.62) in its limited domain than did physician reviewers (0.3-0.56). At least in hypertension management, automated review of computer-based medical records compares favourably with review by physicians. Further development of computer-aided clinical audit requires the introduction of computer-based medical records that capture the reasoning of physicians, and of widely accepted practice guidelines.

Adult

Computer-aided optimization of choice and positioning of bone plates and screws used for internal fixation of mandibular fractures.

The present study describes a biomechanical integrated model of the mandibular system in which the maxilla and mandible, the masticatory muscles, and the temporomandibular joints are regarded as one system. In this model, strains in plate-osteosynthesis devices for internal fixation of mandibular fractures can be minimized by optimizing their positions. The model evaluates maximal bite force strategies on all possible dental elements; it uses a linear programming technique and a muscle architecture model, resulting in muscle recruitment patterns. The shape of a "standard" lower jaw is digitized by means of a three-dimensional (3-D) coordinate retrieval device and drawn on a computer screen after its dimensions have been changed according to the clinical case at hand. The 3-D location of the fracture as well as the anatomic restrictions for screw placement can be indicated on the screen. Osteosynthesis devices can be indicated in terms of dimensions, number, and material properties.

Biomechanical Phenomena

The uses of computer-aided signal peptide selection and polymerase chain reaction in gene construction and expression of secreted proteins.

The computer program, SIGSEQ2, was used to select heterologous signal peptides from a catalog of published sequences to express the echistatin gene in insect (Sf9) cells. S-values for each amino acid were determined to select empirically the site of cleavage between the signal peptide and mature echistatin. Five gene fragments encoding the signal peptides for human immunoglobulin kappa (Ig kappa), Drosophila 68C glue, antistasin, bovine growth hormone (bGH), and human apolipoprotein E (Apo E) were constructed by the use of long synthetic oligonucleotides or polymerase chain reaction (PCR). Echistatin expression vectors then were constructed using the baculovirus polyhedrin promoter. Following transient transfection, the media were assayed for echistatin activity. The results indicate that the computer program greatly facilitated the selection and design of five different signal peptides and accurately predicted their relative functionality in the expression and secretion of echistatin in insect cell cultures.

Animals

The use of modified constellation graph method for computer-aided classification of congenital heart diseases.

This paper describes a new method of data reduction and classification in a multidimensional symptom space for diagnostic aid of congenital heart diseases. The algorithm developed here is to reduce interactively a multidimensional symptom space to sectorial regions representing each disease in a semicircle using the modified constellation graph method. This method enables us to classify patients using the angle in the semicircle as a single classifying parameter with an accuracy of about 90%, that is, with little overlapping between disease sectors. Comparing this method with conventional factor analysis, we have found the former far more effective than the latter for disease region separation.

Algorithms

Bayesian statistics: a guided tour.

An overview of Bayesian statistical decision theory is presented in the tutorial spirit. A section on fundamental principles is followed by selected applications of the Bayesian approach to parameter estimation, pattern recognition, image processing, computer-aided medical diagnosis, optimal diagnostic test selection, and radiotherapy treatment planning.

Decision Making

Patch test results of the Dermatology Clinic Zurich in 1989: personal computer-aided statistical evaluation.

The patch test results of 921 consecutively tested patients were registered on an IBM personal computer. A computer program based on the dBase III plus database software, especially designed for this purpose, was used. The statistical evaluation was performed with dBase III plus. 59% of the probands were females and 41% males. The average age was 42.8 years. 26% of the probands were inpatients and 74% outpatients. A majority of the patients presented with eczema of the hands, face or the lower legs. The largest occupational groups were houseworkers and cleaning personnel, office workers and pensioners. To 450 of the 921 patients, at least 4 test series were applied simultaneously. These included European standard, vehicles and emulgators, topical medications, and preservatives and biocides. The other 20 test series available were employed only by 2-81 patients each. The highest sensitization rates were found with: nickel, 18.7%; cobalt, 10.2%; balsam of Peru, 8.8%; framycetin, 8.0%; neomycin, 6.8%; potassium dichromate, 6.1%; p-phenylene diamine, 5.4%; paramix, 4.9%; formaldehyde, 4.8%, and (chlor)methylisothiazolinone, 4.7%. The critical evaluation of the data showed two kinds of problems: first, test-specific aspects led to optimization of the patch test procedures; second, the crucial importance of an adequate statistical analysis for epidemiological investigation was revealed.

Adolescent

A comparison of conventional intra-oral radiography and computer imaging techniques for the detection of proximal surface dental caries.

The detection of proximal surface caries by the visual interpretation of bitewing radiographs is known to be relatively inaccurate. The present study was designed to examine whether computer image processing could improve the diagnostic accuracy. A computer-aided, software-driven, TV-based system was used to digitize conventional radiographs and digitally process the images using histogram equalization and grey-scale inversion to enhance the images. The computer-enhanced images were compared with conventional intra-oral radiographs for the detection of proximal surface caries using receiver operating characteristic analysis. The results indicate that the digital image processing techniques used did not improve the diagnostic accuracy of dental radiographs. No significant difference in diagnostic accuracy could be detected between the non-enhanced digital images and conventional film-based images for the detection of proximal surface caries.

Dental Caries

[Computer-aided prediction of optimal composition of multicomponent mobile phase in high performance liquid chromatography].

This paper proposed a systematic optimizing method for the composition of multicomponent mobile phase in high performance liquid chromatography. A new chromatographic response function (CRF) has been constructed according to the fundamental retention equation and rule of peak width at half-height, and the optimal composition of multicomponent mobile phase can be automatically predicted by a computer with CRF. This paper improved the known complex method, therefore, the optimal mobile phase composition in the global area may be found by means of this modified complex method. The optimal separation conditions of four vitamins and three nitrophenols were determined by use of the optimizing method reported in this paper. The results predicted by the computer were verified by the experimental data obtained in HPLC using ternary mobile phase.

Chromatography, High Pressure Liquid

Development of a computer-aided reference system for differential diagnostics support.

In a situation of uncertain diagnosis, physicians may spend valuable time consulting relevant literature, often with unsatisfactory results. Therefore, our aim was to develop a computer system which supports differential diagnostics via rapid and comprehensive searches through information in literature. Based on entered signs and symptoms our prototype is able to offer probable diagnoses. Subsequently, further examinations and tests are suggested to confirm or exclude a certain disease. Thus, the final diagnosis is made gradually by differentiation of possible diseases. Our first attempt consisted in representing knowledge in a rule-based PROLOG system. However, because nearly all information for a sign-oriented differential diagnosis can be represented with very few relations only, we turned to a fact-oriented representation of signs and diseases. Access was possible via PROLOG or an imperative programming language. The index-sequential access on a fact-oriented representation of knowledge was suitable to manage a large knowledge base, which is necessary for a thorough differential diagnosis. A pointer structure was recently examined in order to handle different object-to-object relations. Efficient information processing is now possible which provides short response times using even broad knowledge bases.

Diagnosis, Computer-Assisted

Computer assistance in keratoconus lens design.

In the past, keratoconus patients have been custom fit with multi-curve spherical contact lenses. Recently it has become possible to commercially manufacture aspherical contact lenses of high-Dk material. A computer assisted fitting technique may be used with these new lenses. We report 90 consecutive keratoconus eyes that were fit with aspherical high-Dk contact lenses using a computer-aided fitting system. Mild and severe grades of keratoconus cases were included, with a 6 to 12 month follow-up time. The combination of new lens geometry and lens material produced a reduction in corneal complications. The asphericity of the lens geometry had a slight negative influence on the visual acuity in mild keratoconus cases, but the visual acuity in the severe keratoconus cases was good. The contact lens material proved acceptably durable, despite the high oxygen transmissibility. We found the computer assisted fitting technique very accurate in determining the initial fitting lens and much faster than the former trial-and-error procedure.

Contact Lenses