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Biomedical subjects

R M Hall

Publications and source records attributed to R M Hall.

At least 19 recordsLinked to original sources
PubMed2006

The dodecameric vanadium-dependent haloperoxidase from the marine algae Corallina officinalis: cloning, expression, and refolding of the recombinant enzyme.

The dodecameric vanadium-dependent bromoperoxidase from Corallina officinalis has been cloned and over-expressed in Escherichia coli. However, the enzyme was found to be predominantly in the form of inclusion bodies. This protein presents a challenging target for refolding, both due to the size (768kDa) and quaternary structure (12x64kDa). Successful refolding conditions have been established which result in an increase in the final yield of active bromoperoxidase from 0.5mg to 40mg per litre of culture. The refolded protein has been characterised and compared to the native enzyme and was shown to be stable at temperatures of 80 degrees C, over a pH range 5.5-10 and in organic solvents such as ethanol, acetonitrile, methanol, and acetone. The novel refolding approach reported in this paper opens up the full potential of this versatile enzyme for use in large scale biotransformation studies.

Amino Acid Sequence↗
PubMed2006

The biomechanical response of spinal cord tissue to uniaxial loading.

The spinal cord is an integral component of the spinal column and is prone to physical injury during trauma or more long-term pathological insults. The development of computational models to simulate the cord-column interaction during trauma is important in developing a proper understanding of the injury mechanism. Such models would be invaluable in seeking both preventive strategies that reduce the propensity for injury and identifying specific treatment regimes. However, these developments are hampered by the limited information available on the structural and mechanical properties of this soft tissue owing to the difficulty in handling this material in a cadaveric situation. The purpose of the present paper is to report the rapid deterioration in the quality of the tissues once excised, which provides a further challenge to the successful elucidation of the structural properties of the tissue. In particular, the tangent modulus of the tissue is seen to increase sharply over a period of 72 h.

Animals↗
PubMed2004

A dynamic investigation of the burst fracture process using a combined experimental and finite element approach.

Spinal burst fractures account for about 15% of spinal injuries and, because of their predominance in the younger population, there are large associated social and healthcare costs. Although several experimental studies have investigated the burst fracture process, little work has been undertaken using computational methods. The aim of this study was to develop a finite element model of the fracture process and, in combination with experimental data, gain a better understanding of the fracture event and mechanism of injury. Experimental tests were undertaken to simulate the burst fracture process in a bovine spine model. After impact, each specimen was dissected and the severity of fracture assessed. Two of the specimens tested at the highest impact rate were also dynamically filmed during the impact. A finite element model, based on CT data of an experimental specimen, was constructed and appropriate high strain rate material properties assigned to each component. Dynamic validation was undertaken by comparison with high-speed video data of an experimental impact. The model was used to determine the mechanism of fracture and the postfracture impact of the bony fragment onto the spinal cord. The dissection of the experimental specimens showed burst fractures of increasing severity with increasing impact energy. The finite element model demonstrated that a high tensile strain region was generated in the posterior of the vertebral body due to the interaction of the articular processes. The region of highest strain corresponded well with the experimental specimens. A second simulation was used to analyse the fragment projection into the spinal canal following fracture. The results showed that the posterior longitudinal ligament became stretched and at higher energies the spinal cord and the dura mater were compressed by the fragment. These structures deformed to a maximum level before forcing the fragment back towards the vertebral body. The final position of the fragment did not therefore represent the maximum dynamic canal occlusion.

Animals↗
PubMed2003

Determination of the trabecular bone direction from digitised radiographs.

There is increasing evidence for monitoring the bone trabecular structure to explain, in part, the mechanical properties of bone. Despite the emergence of Computed Tomography, a radiograph is the standard format as it is cheap and used for assessing implant performance. Furthermore, various image-processing techniques developed to assess the trabecular structure from radiographs have regained interest owing to improvements in imaging equipment. This study assessed the precision and accuracy of the Co-occurrence and Run-length matrix, Spatial-frequency and Minkowski-fractal techniques to infer the trabecular direction from radiographs. Ten clinical images of femoral neck regions were obtained from digitised pelvic radiographs and subsequently analysed. These data were also used to generate synthetic images where the trabecular thickness, separation and directions were controlled in order to calculate the accuracy of the techniques. Additionally, a Laplacian noise was added in order to infer the precision of the techniques. All methods assessed the trabecular direction with a high degree of accuracy in these synthetic images including a single direction and no noise. However, only the Spatial-frequency and Co-occurrence matrix methods performed well on the clinical and heavily corrupted synthetic images. This demonstrated the possibility of inferring a linear trabecular direction in clinical conditions.

Algorithms↗
PubMed2002

Measurement of canal occlusion during the thoracolumbar burst fracture process.

Post-injury CT scans are often used following burst fracture trauma as an indication for decompressive surgery. Literature suggests, however, that there is little correlation between the observed fragment position and the level of neurological injury or recovery. Several studies have aimed to establish the processes that occur during the fracture using indirect methods such as pressure measurements and pre/post impact CT scans. The purpose of this study was to develop a direct method of measuring spinal canal occlusion during a simulated burst fracture by using a high-speed video technique. The fractures were produced by dropping a mass from a measured height onto three-vertebra bovine specimens in a custom-built rig. The specimens were constrained to deform only in the impact direction such that pure compression fractures were generated. The spinal cord was removed prior to testing and the video system set up to film the inside of the spinal canal during the impact. A second camera was used to film the outside of the specimen to observe possible buckling during impact. The video images were analysed to determine how the cross-sectional area of the spinal canal changed during the event. The images clearly showed a fragment of bone being projected from the vertebral body into the spinal canal and recoiling to the final resting position. To validate the results, CT scans were taken pre- and post-impact and the percentage canal occlusion was calculated. There was good agreement between the final canal occlusion measured from the video images and the CT scans.

Animals↗
PubMed2002

Indications of disordered eating behaviour in adolescent patients with idiopathic scoliosis.

We have investigated whether patients with adolescent-onset idiopathic scoliosis (AIS) are more likely to have a low body-weight. Measurements of weight, height and body mass index (BMI) were made in 44 young women with AIS and compared with age- and gender-adjusted normative data. The body mass criteria of the International Classification of Diseases for eating disorders was used to determine how many patients were within the range considered to be 'eating disordered'. Compared with the normative data, the AIS group did not differ significantly in terms of height, (p = 0.646), but they were significantly lighter (p < 0.001) and had significantly lower BMI scores (p < 0.001); 25% of the series had BMI scores which were within the range considered to be anorexic. The relationship between a diagnosis of AIS and low body-weight may indicate disordered eating and is thus a cause for concern, particularly in the light of the well-established relationship between eating psychopathology and osteoporosis. Aspects of organic health may need to be considered in addition to the cosmetic deformity.

Adolescent↗
PubMed2001

Family of class 1 integrons related to In4 from Tn1696.

The class 1 integron In28, found in the multidrug resistance transposon Tn1403, was found to be located in the res site of the backbone transposon and is flanked by a 5-bp direct duplication, indicating that it reached this position by transposition. In28 has a backbone structure related to that of In4, but has lost internal sequences, including the sul1 gene, due to an IS6100-mediated deletion. In28 also lacks the partial copy of IS6100 found in In4 and contains different gene cassettes, blaP1, cmlA1, and aadA1. In1, the class 1 integron found in the multidrug resistance plasmid R46, is also located in a putative res site and belongs to the In4 group. In1 has a shorter internal deletion than In28 and has also lost one end. Additional integrons with structures related to In4 were also found in databases, and most of them had also lost either one end or internal regions or both. Tn610 belongs to this group.

Base Sequence↗
PubMed2001

Transposons Tn1696 and Tn21 and their integrons In4 and In2 have independent origins.

The first 13.6 kb of the mercury and multidrug resistance transposon Tn1696, which includes the class 1 integron In4, has been sequenced. In4 is 8.33 kb long and contains the 5'-conserved segment (5'-CS) and 2.24 kb of the 3'-conserved segment (3'-CS) flanking four integrated cassettes. The 3'-CS region is followed by one full copy and an adjacent partial copy of the insertion sequence IS6100 flanked, in inverse orientation, by two short segments (123 and 152 bp) from the outer right-hand end of class 1 integrons. This structure is representative of a distinct group of class 1 integrons that differs from In2, found in Tn21, and other related class 1 integrons. In4 does not include transposition genes but is bounded by characteristic 25-bp inverted repeats and flanked by a direct duplication of 5 bp of the target sequence, indicating that it was inserted by a transpositional mechanism. In4 lies between the resII and resI sites of a backbone mercury resistance transposon which is >99.5% identical to Tn5036. Although Tn21 and Tn1696 are both classified as members of the Tn21 subfamily of the Tn3 transposon family, the backbone mercury resistance transposons are only 79 to 96% identical. Tn21 also contains a region of about 0.7 kb not found in Tn1696. The integrons In2 and In4 carrying the antibiotic resistance genes have been inserted at different locations into distinct ancestral mercury resistance transposons. Thus, Tn21 and Tn1696 have independent histories and origins. Other transposons (Tn1403 and Tn1412) that include a class 1 integron also have independent origins. In all except Tn21, the integron is located within the res region of the backbone transposon.

Anti-Infective Agents, Local↗
PubMed2001

Efficiency of recombination reactions catalyzed by class 1 integron integrase IntI1.

The class 1 integron integrase, IntI1, recognizes two distinct types of recombination sites, attI sites, found in integrons, and members of the 59-be family, found in gene cassettes. The efficiencies of the integrative version of the three possible reactions, i.e., between two 59-be, between attI1 and a 59-be, or between two attI1 sites, were compared. Recombination events involving two attI1 sites were significantly less efficient than the reactions in which a 59-be participated, and the attI1 x 59-be reaction was generally preferred over the 59-be x 59-be reaction. Recombination of attI1 with secondary sites was less efficient than the 59-be x secondary site reaction.

Attachment Sites, Microbiological↗
PubMed2001

The effect of socket design, materials and liner thickness on the wear of the porous coated anatomic total hip replacement.

The wear of joint replacement prostheses represents the greatest challenge to their continued development. Parameters such as polyethylene quality, liner thickness and metal backing have all been implicated as potential detractors in the search for the lowest-wearing socket. This study examined the effect of these parameters through an extensive study of the two versions of the porous coated anatomic (PCA) hip prosthesis (one-piece socket and snaplock socket). For the whole cohort the wear rate was found to be 88 (SE 10) mm3/year and the clinical wear factor was 2.00 (SE 0.28) x 10(-6) mm3/N m. When the two socket types were investigated individually, the wear factors found were 2.39 (SE 0.44) x 10(-6)mm3/N m and 0.99 (SE 0.25) x 10(-6) mm3/N m for the one-piece and snaplock, respectively. This illustrates that the metal backing per se does not predispose these sockets to rapid wear. The good wear performance of the snaplock liner may be attributed to the high quality of the ultra-high molecular weight polyethylene (UHMWPE) used and the shorter implantation period compared to that for the one-piece design. No correlation was found between the thickness of the liner and the clinical wear factor. Within the range of thicknesses tested here, UHMWPE thickness is not an influential parameter for the hip prosthesis and this is confirmed

Arthroplasty, Replacement, Hip↗
PubMed2001

The production of novel sordarin analogues by biotransformation.

The biotransformation of the fungal protein synthesis inhibitor sordarin is reported. Nine taxonomically diverse organisms supported the isolation and identification of twelve modified products. The structural diversity of the biotransformation products observed and their value in supporting further chemistry is discussed.

Antifungal Agents↗
PubMed1999

Characterisation of a chloramphenicol acetyltransferase determinant found in the chromosome of Pseudomonas aeruginosa.

The open reading frame (ORF) in the Pseudomonas aeruginosa chromosome, whose product resembles the chloramphenicol acetyltransferases (CAT) belonging to the CATB family, was cloned and shown to confer resistance to chloramphenicol (Cm) in Escherichia coli. The determinant was therefore named catB7 and the corresponding protein CATB7. When the copy number and expression signals were identical, the catB7 gene conferred resistance to Cm at a level slightly lower than those of three other catB genes. CATB7 resembles other CATBs in that it acetylates Cm but not 1-acetoxy-Cm. For CATB7, the K(m) values for acetyl-CoA and Cm were 5.0-5.4-fold higher than the corresponding values for each of the three other CATB proteins (CATB1, CATB3 and CATB5) examined and the Vmax was 5-6 fold lower. Using PCR, the catB7 gene was found in all six P. aeruginosa strains examined but not in any other species of pseudomonad tested. Weak CAT activity was detected in crude cell extracts from five of the six P. aeruginosa strains. However, this activity did not correlate with the Cm susceptibility of the strains, indicating that catB7 is not likely to be the major determinant of intrinsic Cm resistance in P. aeruginosa.

Amino Acid Sequence↗
PubMed1999

Mobile gene cassettes and integrons in evolution.

Integrons and the site-specific recombination systems encoded by them provide a simple mechanism for the addition of new genes to bacterial chromosomes. Although there is substantial divergence among the four known integron-encoded integrases, they all recognize the recombination sites, known as 59-base elements, that are associated with genes that are packaged in gene cassettes. In contrast, the integron-associated recombination sites, attl sites, are preferentially recognized by the cognate integrase.

Base Sequence↗
PubMed1999

The influence of femoral head surface roughness on the wear of ultrahigh molecular weight polyethylene sockets in cementless total hip replacement.

A theoretical relationship was recently proposed relating the wear behavior of polymetric bearing materials articulating against hard counterfaces.(1) This model attempts to predict the influence of surface roughness on wear. Laboratory-based studies have been used to establish the validity of these relationships, but their application to the clinical situation has not been investigated fully. Forty-two retrieved PCA hip joints have been assessed. The total wear volume was calculated from the penetration measured using the shadowgraph method, and roughness of the articulating surfaces was recorded using noncontacting profilometry. The roughness of the explanted femoral heads was observed to increase (median S(a) - 10. 35 nm worn region, 3.05 nm peripheral region), while that of the acetabular liner fell dramatically (median S(a) - 41 nm worn region, 212 nm unworn region). No evidence of a relationship between the topography of the worn regions of the femoral head and that of the acetabular liner could be found. Similarly, the strength of the association between the surface roughness and the clinical wear factor was considerably poorer than that achieved in laboratory experiments. A number of reasons for this observation are proposed. Most deleterious was considered to be the inability of the roughness parameters to describe the damaging features of the surface adequately. Uncertainty as to when the surface of the component degrades during its life serves to introduce further doubt as to the application of the wear models in the clinical environment. In conclusion, this study fails to provide clinical evidence to substantiate the relationship between surface finish and wear rate. The adoption of standardized measurement parameters and techniques would facilitate the direct comparison of joint types and the selection of the most advantageous materials.

Arthroplasty, Replacement, Hip↗