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Austin T. Moore designed a little-known prototype press-fit distal femoral resurfacing knee prosthesis. The implant's history and its long-term follow-up result in one existing patient are reported in the 51st anniversary year of Dr. Moore's first prosthetic procedure.
BACKGROUND: Rapid image acquisition after cessation of exercise is essential for accurate stress echocardiography. Recently, a prototype matrix-array transducer has been developed that allows simultaneous acquisition of 2 imaging planes (biplane [BP] imaging). METHODS: In all, 19 healthy volunteers underwent 2 separate stress echocardiographic studies. Images were acquired in traditional 2-dimensional or BP format pre-exercise and postexercise. RESULTS: Total image acquisition time for 2-dimensional stress echocardiography was 38 +/- 8 seconds versus 29 +/- 8 seconds for BP imaging (P <.05). Heart rates were acquired closer to age-predicted maximum with BP imaging in the apical 3- and 2-chamber and parasternal long- and short-axis views (82%, 75%, 70%, 70% for BP vs 76%, 72%, 68%, 66% for 2-dimensional, respectively). CONCLUSION: BP imaging using a recently developed matrix-array probe allows more rapid imaging postexercise, resulting in acquisition of poststress images at higher heart rates without compromising image quality.
The present study tested the therapeutic potential for prototype anti-epilepsy drugs using an animal model of infantile febrile seizures. The model consisted of immersion of weanling rats (21 days old) in a 45 degrees C water bath for a maximum of 4 min (four exposures over a 2 week period) and observing for the progression to stage-5 seizures. All compounds were administered orally at the respective ED50 for prevention of seizures in the maximal electroshock (MES) test. Clonazepam effectively lowered the score for seizure grade, shortened the duration of seizures, as well as reduced the number of animals experiencing seizures during three of the four testing periods. MK801 reduced both the maximum seizure grade, and the number of animals experiencing seizures during sessions two and three. However, the dose of MK801 caused behavioral side effects. Valproate actively decreased seizure grade, while it modestly acted to attenuate seizure duration, extended the time to seizure onset, and reduced the number of animals experiencing seizures on testing day 1. Remacemide hydrochloride and phenobarbital were not effective. The method appears useful for evaluating the potential of agents to prevent acute febrile seizures.
Restriction site maps with the endonucleases BamHI, BgIII, and HindIII were elaborated for 19 adenovirus strains of subgenus D, namely candidates AV42 to 47, 6 intermediate and 7 atypical strains. On the basis of several types mapped by biochemical methods, the physical maps for the 19 strains were constructed by adapting restriction fragments of defined molecular weight to the known maps, as the homology among strains within this subgenus is considerable. Other prototypes mapped by adaptation were also used for reference. The localization of the restriction sites on the genome was analyzed for all mapped types or strains of subgenus D (except AV8). The sites appeared to be randomly distributed; only one site was common to all strains.
Collagenous transmembrane proteins are an emerging group of biologically versatile molecules which function as both cell surface receptors and matrix molecules. The seven group members have interesting structural similarities: they are integral membrane proteins in type II orientation and have one or more collagenous domains in the extracellular C-terminus; interspersed by non-collagenous stretches which confer structural flexibility to the ectodomain. A conserved coiled-coil sequence (linker domain) immediately adjacent to the extracellular face of the cell membrane presumably serves as a nucleus for trimerization and triple-helix folding of each collagen. Intriguingly, the ectodomains of at least some of these molecules are proteolytically shed from the cell surface, releasing a shorter form of the collagen into the extracellular matrix. Collagenous transmembrane proteins are expressed in many different tissues and cells, and are involved in a broad spectrum of biological functions, reaching from epithelial and neural cell adhesion, and epithelial-mesenchymal interactions during morphogenesis to host defense against microbial agents. Several group members are involved in the molecular pathology of genetic and acquired human diseases including epidermolysis bullosa, ectodermal dysplasia, bullous pemphigoid or Alzheimer disease. An extensively investigated member is collagen XVII, a keratinocyte surface protein, which attaches the epidermis to the basement membrane in the skin. In this review, the structure and functions of the currently known collagenous transmembrane proteins are summarized and, as a 'prototype' of the group, collagen XVII and its biology and pathophysiology are delineated.
The capacity factor of eleven derivatives belonging to a prototype series of 3-phenyloxazolidin-2-one, reversible MAO inhibitors, was measured and compared to the calculated log Pcalc using the CLIP package. We demonstrate that this Molecular Lipophilicity Potential (MLP) approach is a valuable tool to estimate log Pcalc of such compounds.
Calmodulin is the best studied and prototypical example of the E-F-hand family of Ca2+-sensing proteins. Changes in intracellular Ca2+ concentration regulate calmodulin in three distinct ways. First, at the cellular level, by directing its subcellular distribution. Second, at the molecular level, by promoting different modes of association with many target proteins. Third, by directing a variety of conformational states in calmodulin that result in target-specific activation. The calmodulin-dependent regulation of protein kinases illustrates the potential mechanisms by which Ca2+-sensing proteins can recognize and generate affinity and specificity for effectors in a Ca2+-dependent manner.
BACKGROUND: Rhodanese domains are structural modules occurring in the three major evolutionary phyla. They are found as single-domain proteins, as tandemly repeated modules in which the C-terminal domain only bears the properly structured active site, or as members of multidomain proteins. Although in vitro assays show sulfurtransferase or phosphatase activity associated with rhodanese or rhodanese-like domains, specific biological roles for most members of this homology superfamily have not been established. RESULTS: Eight ORFs coding for proteins consisting of (or containing) a rhodanese domain bearing the potentially catalytic Cys have been identified in the Escherichia coli K-12 genome. One of these codes for the 12-kDa protein GlpE, a member of the sn-glycerol 3-phosphate (glp) regulon. The crystal structure of GlpE, reported here at 1.06 A resolution, displays alpha/beta topology based on five beta strands and five alpha helices. The GlpE catalytic Cys residue is persulfurated and enclosed in a structurally conserved 5-residue loop in a region of positive electrostatic field. CONCLUSIONS: Relative to the two-domain rhodanese enzymes of known three-dimensional structure, GlpE displays substantial shortening of loops connecting alpha helices and beta sheets, resulting in radical conformational changes surrounding the active site. As a consequence, GlpE is structurally more similar to Cdc25 phosphatases than to bovine or Azotobacter vinelandii rhodaneses. Sequence searches through completed genomes indicate that GlpE can be considered to be the prototype structure for the ubiquitous single-domain rhodanese module.
N-Acetyl-L-glutamate kinase (NAGK), a member of the amino acid kinase family, catalyzes the second and frequently controlling step of arginine synthesis. The Escherichia coli NAGK crystal structure to 1.5 A resolution reveals a 258-residue subunit homodimer nucleated by a central 16-stranded molecular open beta sheet sandwiched between alpha helices. In each subunit, AMPPNP, as an alphabetagamma-phosphate-Mg2+ complex, binds along the sheet C edge, and N-acetyl-L-glutamate binds near the dyadic axis with its gamma-COO- aligned at short distance from the gamma-phosphoryl, indicating associative phosphoryl transfer assisted by: (1) Mg2+ complexation; (2) the positive charges on Lys8, Lys217, and on two helix dipoles; and (3) by hydrogen bonding with the y-phosphate. The structural resemblance with carbamate kinase and the alignment of the sequences suggest that NAGK is a structural and functional prototype for the amino acid kinase family, which differs from other acylphosphate-making devices represented by phosphoglycerate kinase, acetate kinase, and biotin carboxylase.
BACKGROUND: Translation initiation factor 4A (elF4A) is the prototype of the DEAD-box family of proteins. DEAD-box proteins are involved in a variety of cellular processes including splicing, ribosome biogenesis and RNA degradation. Energy from ATP hydrolysis is used to perform RNA unwinding during initiation of mRNA translation. The presence of elF4A is required for the 43S preinitiation complex to bind to and scan the mRNA. RESULTS: We present here the crystal structure of the nucleotide-binding domain of elF4A at 2.0 A and the structures with bound adenosinediphosphate and adenosinetriphosphate at 2.2 A and 2.4 A resolution, respectively. The structure of the apo form of the enzyme has been determined by multiple isomorphous replacement. The ATPase domain contains a central seven-stranded beta sheet flanked by nine alpha helices. Despite low sequence homology to the NTPase domains of RNA and DNA helicases, the three-dimensional fold of elF4A is nearly identical to the DNA helicase PcrA of Bacillus stearothermophilus and to the RNA helicase NS3 of hepatitis C virus. CONCLUSIONS: We have determined the crystal structure of the N-terminal domain of the elF4A from yeast as the first structure of a member of the DEAD-box protein family. The complex of the protein with bound ADP and ATP offers insight into the mechanism of ATP hydrolysis and the transfer of energy to unwind RNA. The identical fold of the ATPase domain of the DNA helicase PcrA of B. stearothermophilus and the RNA helicase of hepatitis C virus suggests a common fold for all ATPase domains of DExx- and DEAD-box proteins.
A prototype in vivo total body composition analyser has been constructed for determining the total body contents of nitrogen (TBN), carbon (TBC) and oxygen (TBO) in young experimental animals such as sheep or pigs by 14 MeV neutron activation using a commercially available associated particle sealed tube neutron generator (APSTNG). The instrument was calibrated by scanning phantoms of different sizes in the mass range 10-36 kg, filled with a mixture of elements as found in a normal human body. Good agreement was found between the measured and expected values of N, O and C when two phantoms of similar dimensions but of different composition were scanned. With four 15 cm x 15 cm cross section and 45 cm long NaI(T1) gamma detectors and a radiation dose of approximately 20 microSv due to neutrons, the expected precisions for a 28 kg animal, CV% (based on counting statistics) are N: 9.3, C: 2.3 and O: 1.4.
The aim of this study was to mechanically characterize self-tapping 2.3 and 2.7 mm titanium lag screw prototypes which are part of the newly developed 'self-adapting washer' maxillofacial lag screw osteosynthesis system. In vitro in a screw testing machine the insertion torque, maximum locking torque and axial force and the ultimate torsional strength were assessed. In vivo in six miniature pigs using a mandibular symphyseal fracture model, the removal torques after 3 and 6 months of healing were measured. Additionally the bone-metal contact (BMC) of the screws was assessed histometrically. The maximum insertion torque (0.185 Nm) was far below the mechanical limits of the screws (2.3 mm = 0.96 Nm, 2.7 mm = 1.6 Nm). A tightening of the 2.7 mm screw with an axial force of 1000 N and of the 2.3 mm screw with 500-550 N leaves a safety margin of approximately one-third on the ultimate torsional strength. Clinically these values permit the use of two 2.3 mm lag screws or one 2.7 mm lag screw in mandibular symphysis fractures since 1000 N tensile axial force are required in this indication. During screw removal after 6 months healing, torque levels close to the mechanical limits of the screws were recorded and screw failures were observed. This failure rate may have been due to the BMC of 49.8% which was in the range of titanium dental implants. Accordingly the screw heads were reinforced to prevent fractures.
A prototype simulator for training in endovascular repair of abdominal aortic aneurysms (AAA) has been developed. Employing transparent models of human AAA complete with renal, iliac and femoral arteries, this system allows accurate simulation of aortography, road-mapping, catheter guidewire manipulation and stent-graft deployment while obviating the need for ionising radiation.
Rapid prototyping techniques, originally developed for building components from computer aided designs in the motor industry, are now being applied in medicine to build models of human anatomy from high resolution multiplanar imaging data such a computed tomography (CT). The established technique of stereolithography and the more recent selective laser sintering (SLS), both build up an object layer by layer. Models have applications in surgical planning, for the design of customised implants and for training. Preliminary experience of using the SLS technique for medical applications is described, addressing questions regarding image processing, data transfer and manufacture. Pilot models, built from nylon, included two skills (a child with craniosynoslosis and an adult with hypertetorism) and a normal femur which was modelled for use in a bioengineering test of an artificial hip. The dimensions of the models were found to be in good agreement with the CT data from which they were built-for the child's skull the difference between the model and the CT data was less than 1.0 +/- 0.5 mm in each direction. Our experience showed that, with care, a combination of existing software packages may be used for data conversion. Ideally, image data of high spatial resolution should be used. The pilot models generated sufficient clinical interest for the technique to be pursued in the orthopaedic field.
The support services for biomedical technology address a variety of technical and administrative issues, concerning the safe and efficient operation of medical equipment over the period of its intended use and the training of hospital personnel in issues concerning safety and quality. Clinical Engineering Departments undertake the responsibility of developing and operating training programs in medical equipment utilisation apart from the traditional role of training and supervising technicians involved in testing, calibration and preventive/corrective maintenance of electromedical equipment. In view of the above, the Institute of Biomedical Technology and the Centre of Biomedical Engineering collaborated for the design and development of a prototype digital ECG and arrhythmia simulator. In the absence of internationally accepted inspection protocols for ECG simulators, the verification phase of the project involved mainly the inspection of the device's conformity to its initial technical specifications. The results demonstrated that this tester. due to simplicity in construction and easiness of use could be a practical, reliable and economical solution for electrocardiograph and ECG monitor testing and waveform recognition training.
IT support for home health care is an expanding area within health care IT development. Home health care differs from other in- or outpatient care delivery forms in a number of ways, and thus, the introduction of home health care applications must be based on a rigorous analysis of necessary requirements to secure safe and reliable health care. This article reports early experiences from the development of a home health care application based on emerging JAVA technologies. A prototype application for the follow-up of diabetes patients is presented and discussed in relation to a list of general requirements on home health care applications.
Serine palmitoyltransferase (SPT, EC 2.3.1.50) is a key enzyme in sphingolipid biosynthesis and catalyzes the decarboxylative condensation of L-serine and palmitoyl coenzyme A (CoA) to 3-ketodihydrosphingosine (KDS). We found that the gram-negative obligatory aerobic bacteria Sphingomonas paucimobilis EY2395(T) have significant SPT activity, and purified SPT to homogeneity. Unlike eukaryotic enzymes, this enzyme was a water-soluble homodimeric protein. We isolated the SPT gene encoding 420 amino acid residues (M(r) 45,041) and succeeded in overproducing the SPT protein in Escherichia coli, in which the product amounted to about 10-20% of the total protein of the cell extract. Sphingomonas SPT showed about 30% homology with the enzymes of the alpha-oxamine synthase family, and amino acid residues supposed to be involved in catalysis are conserved. The purified recombinant-SPT showed the characteristic absorption spectrum derived from its coenzyme pyridoxal 5'-phosphate (PLP). The addition of the substrate, L-serine, caused spectral changes indicating the formation of the external aldimine intermediate. Sphingomonas SPT is a prototype of the eukaryotic enzyme and would be a useful model to elucidate the reaction mechanism of SPT.
Sera of 197 apparently well persons were tested for residual haemagglutination-inhibiting antibodies against live Hong Kong/68, A/FM/47 and A/PR/34 strains. Sera of 62 well persons, regularly exposed to contacts with swine, were tested against an inactivated A/New Jersey/76 antigen. Those born some time before and during a certain influenza era showed a significantly greater proportion of homologous residual titres against the subtype prevailing in that influenza era, than those born after the termination of the same era. In each of the seven age groups tested both the percentage of positives and the geometric mean titres were usually highest against the Hong Kong strain (representing the most recent era); the next highest were those against the FM1 strain and the lowest were those against the PR8 strain (representing the most distant of these three influenza eras). The serological involvement of donors exposed to regular contacts with swine was relatively stronger against the New Jersey antigen than the response of other serum donors shown against the other three, more recent, prototypes of influenza virus A. The oldest age groups showed significantly lower antibody response against the PR8, FM1 and Hong Kong strains (but not against the New Jersey antigen) than the next one or two of the younger age groups.