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Biomedical subjects

William R Taylor

Publications and source records attributed to William R Taylor.

At least 19 recordsLinked to original sources
PubMed2006

Dynamic domain threading.

A modeling method is described that avoids the need to consider the domain structure of the template used for modeling, and automatically extracts compact fragments of structure that would be of a suitable size to build the model. This aids automation as the size or nature of the template structure can be ignored and does not have to be broken into domain (or multi-domain) units beforehand. The approach leads to the generation of a large number of models each based on slightly differing domain definitions and this variation was further increased by considering alternative secondary structure predictions. Each model, of which there may be thousands, takes the form of a complete alpha-carbon trace and some methods (including residue burial) were investigated for their power to discriminate good models from bad models using decoys. The method is also compared to an earlier retroviral capsid modeling problem for which the X-ray structure is now known. Some potential extensions of the approach to more distant modeling problems are discussed.

Algorithms↗
PubMed2006

Coblation of spinal endplates in preparation for interbody spinal fusion.

Posterior lumbar interbody fusion (PLIF) and anterior lumbar interbody fusion (ALIF) have become routine alternatives to intertransverse process fusion. The use of Coblation (ArthroCare Corporation, Sunnyvale, CA) allows for routine and reproducible removal of cartilaginous endplate down to the bony endplate. Our experience with this new technology is reviewed. The authors used Coblation to prepare endplates of 10 consecutive patients undergoing interbody fusion. The results were compared to the following 10 consecutive patients undergoing interbody fusion with endplates prepared in the standard fashion with curettes and rongeurs. The same interbody grafts and instrumentation were used in all patients. Follow-up X-rays were done at 1 week, 6 weeks, 6 months, 1 year, and then each year thereafter. The 20 patients were reviewed along with their films. In each patient the disk spaces and the ALIF/PLIF cages appeared to be fused by 6 months. There was one superficial wound infection in each group. In each of the cases in which PLIF was performed, the cages were augmented by posterior lateral graft and pedicle screw fixation. All patients in both groups reported improvement in pain and/or neurologic symptoms by 6 months. The patients were followed for 4.6 years in the Coblation group and 4.1 years in the standard group. Disk space height was measured in all patients at 6 months. In the Coblation group, average disk space height was 9.0 mm compared to 8.2 mm in the standard group (p<0.1). We feel that the maintenance of normal structures within the lumbar spine with anterior/posterior lumbar interbody fusions and non-mechanical means of preparing the endplates are advantageous. Clearly, the number of patients involved and the length of follow-up limit this study, but it serves as an early indicator that endplate preparation may play a role in graft subsidence and fusion rates. Additional study is warranted.

Adult↗
PubMed2006

Mechanical conditions in the initial phase of bone healing.

BACKGROUND: Bone healing is sensitive to the initial mechanical conditions with tissue differentiation being determined within days of trauma. Whilst axial compression is regarded as stimulatory, the role of interfragmentary shear is controversial. The purpose of this study was to determine how the initial mechanical conditions produced by interfragmentary shear and torsion differ from those produced by axial compressive movements. METHODS: The finite element method was used to estimate the strain, pressure and fluid flow in the early callus tissue produced by the different modes of interfragmentary movement found in vivo. Additionally, tissue formation was predicted according to three principally different mechanobiological theories. FINDINGS: Large interfragmentary shear movements produced comparable strains and less fluid flow and pressure than moderate axial interfragmentary movements. Additionally, combined axial and shear movements did not result in overall increases in the strains and the strain magnitudes were similar to those produced by axial movements alone. Only when axial movements where applied did the non-distortional component of the pressure-deformation theory influence the initial tissue predictions. INTERPRETATION: This study found that the mechanical stimuli generated by interfragmentary shear and torsion differed from those produced by axial interfragmentary movements. The initial tissue formation as predicted by the mechanobiological theories was dominated by the deformation stimulus.

Biomechanical Phenomena↗
PubMed2006

An unusual choanoflagellate protein released by Hedgehog autocatalytic processing.

Hedgehog proteins are important cell-cell signalling proteins utilized during the development of multicellular animals. Members of the hedgehog gene family have not been detected outside the Metazoa, raising unanswered questions about their evolutionary origin. Here we report a highly unusual hedgehog-related gene from a choanoflagellate, a close unicellular relative of the animals. The deduced C-terminal domain, Hoglet-C, is homologous to the autocatalytic domain of Hedgehog proteins and is predicted to function in autocatalytic cleavage of the precursor peptide. In contrast, the N-terminal Hoglet-N peptide has no similarity to the signalling peptide of Hedgehog (Hh-N). Instead, Hoglet-N is deduced to be a secreted protein with an enormous threonine-rich domain of unprecedented size and purity (over 200 threonine residues) and two polysaccharide-binding domains. Structural modelling reveals that these domains have a novel combination of features found in cellulose-binding domains (CBD) of types IIa and IIb, and are expected to bind cellulose. We propose that the two CBD domains enable Hoglet-N to bind to plant matter, tethering an amorphous nucleophilic anchor, facilitating transient adhesion of the choanoflagellate cell. Since Hh-C and Hoglet-C are homologous, but Hh-N and Hoglet-N are not, we argue that metazoan hedgehog genes evolved by fusion of two distinct genes.

Amino Acid Sequence↗
PubMed2006

Decoy models for protein structure comparison score normalisation.

A method is described to construct sets of decoy models that can be used to generate a background score distribution for protein structure comparison. The models are derived directly from the two proteins being compared and retain all the essential properties of the structures, including length, density, shape and secondary structure composition but have different folds. As each comparison involves a pair of proteins of the same length, no explicit normalisation is required to adjust for the length of the proteins being compared. This allows substructure (or domain) matches to score almost equally to the comparison of isolated domains. A normalised probability measure was derived that allows joint family/family comparison. The method was applied to some of the CASP6 models for targets with new folds.

Algorithms↗
PubMed2006

Lumbar diskectomy in a human-habituated mountain gorilla (Gorilla beringei beringei).

The authors report a case of a human-habituated mountain gorilla, Alvila, resident at the San Diego Zoo, who was found to have a herniated intervertebral lumbar disc after being attacked by the gorilla troop's silverback male gorilla. Ultimately, the gorilla required surgical intervention for her disease and made a full recovery. To our knowledge, this is the only known case of spine surgery. A 36-year-old female human-habituated mountain gorilla (Gorilla beringei beringei), resident at the San Diego Zoo, was noticed by caregivers to walk with a substantial limp after being attacked by the gorilla troop's silverback male gorilla. Magnetic resonance (MR) imaging of her lumbar spine revealed a large herniated disk at the L1-2 level on the right. This finding appeared to correlate well with the gorilla's symptoms. The gorilla underwent a lumbar diskectomy under loupe. Post-operatively the gorilla did very well. The right leg weakness was immediately improved post-operatively. The gorilla continued to "crutch walk" initially, swinging on the upper extremities and not bearing weight on the lowers. However, by 2 weeks the limp was no longer noticeable to the zoo caregivers. The wound healed well and there was no evidence of wound infection or CSF leak. The gorilla was reunited with her troop and has reintegrated well socially. With 10 months of follow-up, the gorilla continues to do well. This is the only known case of spine surgery in a gorilla. For best surgical results, one needs to consider the similarities and differences between the gorilla and human vertebral anatomy. We believe that careful pre-operative planning contributed to the good early post-operative result. Ultimate assessment of the long-term outcome will require additional follow-up.

Animals↗
PubMed2006

Tibio-femoral joint contact forces in sheep.

Although the sheep has become a standard model for understanding the mechanical conditions that occur after injury and investigating surgical treatments such as osteochondral defect healing and ligament reconstruction, no study has yet evaluated the contact forces that occur in the sheep tibio-femoral joint in vivo. In this study, bone pins, together with reflective markers, were used to measure the 3D kinematics of three sheep hind limbs, simultaneously with the ground reaction forces during repetitions of gait trials. Joint contact forces were then calculated using inverse dynamics and optimisation techniques. Whilst average peak axial tibio-femoral contact forces of 2.1 body weight (BW) were calculated across the 3 sheep, only small medio-lateral and antero-posterior shear forces, averaging 0.7 BW, were determined. Average knee flexion angles ranging from 49 degrees to 70 degrees were observed. From the forces determined in this study, we have provided a better understanding of the mechanical loading environment that occurs in sheep. This has important implications for the interpretation of knee studies in quadrupeds and their relevance to the clinical situation.

Animals↗
PubMed2006

Prolonged Jackson-Pratt drainage in the management of lumbar cerebrospinal fluid leaks.

BACKGROUND: Cerebrospinal fluid (CSF) leak is a complication of spinal surgery. Intraoperative or postoperative identification of a CSF leak often results in wound healing complications, lumbar drain placement, and/or reoperation. These complications usually extend a patient's hospital stay, can be painful, and have their own associated risks. The authors describe a technique that may improve on traditional interventions by managing postoperative CSF leaks after lumbar instrumentation without an additional procedure or extended hospitalization. METHODS: A retrospective review of lumbar instrumentation cases performed by 5 attending surgeons from the Division of Neurosurgery, University of California at San Diego, was performed. In all, 184 charts were reviewed, spanning a 3-year period. There were 16 cases in which a dural tear and repair were carried out and subsequently treated with subfascial Jackson-Pratt (JP) drainage. Of those 16 cases, 8 patients were managed with prolonged JP drainage using the intraoperatively placed subfascial drain. Patients were discharged home on oral antibiotics according to the customary criteria with the JP drain in place and were instructed regarding proper drain maintenance. Jackson-Pratt drains were removed in clinic in a delayed fashion, approximately 10 to 17 days postoperatively. Patients were subsequently reevaluated at regular intervals for any persistent CSF leak. RESULTS: In the 8 cases reviewed, all patients were discharged in a time frame comparable to that of patients undergoing similar instrumentation in which no CSF leak was identified, or in whom a CSF leak was identified and repaired intraoperatively. No patients suffered complications arising from prolonged drain presence. No patients suffered from persistent CSF leak after drains were removed. CONCLUSION: Our study suggests that routine intraoperative subfascial JP drain placement aids in the early diagnosis of postoperative lumbar CSF leak. Primary closure of dural tear remains the standard of care. Furthermore, in select cases, prolonged JP drainage in the setting of postoperative CSF leak may be a useful technique for the treatment of these leaks.

Adult↗
PubMed2006

Control of the G2/M transition.

The G2 checkpoint prevents cells from entering mitosis when DNA is damaged, providing an opportunity for repair and stopping the proliferation of damaged cells. Because the G2 checkpoint helps to maintain genomic stability, it is an important focus in understanding the molecular causes of cancer. Many different methods have been used to investigate the G2 checkpoint and uncover some of the underlying mechanisms. Because cell cycle controls are highly conserved, a remarkable synergy between the genetic power of model organisms and biochemical analyses is possible and has uncovered control mechanisms that operate in many diverse species, including humans. CDC2, the cyclin-dependent kinase that normally drives cells into mitosis, is the ultimate target of pathways that mediate rapid arrest in G2 in response to DNA damage. Additional pathways ensure that the arrest is stably maintained. When mammalian cells contain damaged DNA, the p53 tumor suppressor and the Rb family of transcriptional repressors work together to downregulate a large number of genes that encode proteins required for G2 and M. Elimination of these essential cell cycle proteins helps to keep the cells arrested in G2.

Animals↗
PubMed2005

A survey of formal methods for determining the centre of rotation of ball joints.

The determination of an accurate centre of rotation (CoR) from segment marker positions is of interest across a wide range of applications, but particularly for clinical gait analysis and for estimating the hip joint centre during surgical intervention of the knee, for limb alignment purposes. For the first time in this survey of formal methods, we classify, analyse and compare different methods (geometric, algebraic, bias compensated algebraic, and Pratt sphere fit methods, as well as the centre transformation technique, the Holzreiter approach, the helical pivot technique, the Schwartz transformation techniques, the minimal amplitude point method and the Stoddart approach) for the determination of spherical joint centres from marker position data. In addition, we propose a new method, the symmetrical CoR estimation or SCoRE, in which the coordinates of the joint centre must only remain constant relative to each segment, thus not requiring the assumption that one segment should remain at rest. For each method, 1000 CoR estimations were analysed with the application of isotropic, independent and identically distributed Gaussian noise (standard deviation 0.1cm) to each of the marker positions, to all markers on the segment simultaneously and the two in combination. For the test conditions used here, most techniques were capable of determining the CoR to within 0.3 cm, as long as the spherical range of motion (RoM) of the joint was 45 degrees or more. Under the most stringent conditions tested, however, the SCoRE was capable of best determining the CoR, to within approximately 1.2mm with a RoM of 20 degrees . The correct selection and application of these methodologies should help improve the accuracy of surgical navigation and clinical kinematic measurement.

Biomechanical Phenomena↗
PubMed2005

Minimally-invasive technique for transforaminal lumbar interbody fusion (TLIF).

Minimal access surgical techniques have been described for diskectomy and laminectomy procedures performed through tubular exposures. Tubular exposures, however, restrain visibility to a fixed diameter and require co-axial instrument manipulation. An independent blade retractor system has been developed to overcome the obstacles of working through a tube. Decompression and circumferential fusion can be accomplished through this minimal access exposure via a combination of laminectomy and transforaminal lumbar interbody fusion (TLIF) coupled with minimally invasive pedicle screw fixation. Herein, we describe a minimally-invasive technique for TLIF exposure. Illustrations, intraoperative photographs, and fluoroscopic images supplement this technique. We found that the described minimally-invasive system provides comparable exposure to the traditional-open techniques with the benefits of minimally-invasive techniques. Additionally, it does not have the added constraints of a tubular system. We were able to perform TLIFs without any additional complications. Minimal access decompression and TLIF can be performed safely and effectively using this minimally-invasive system. Besides the retractor system, no additional specialized instruments are required. An operative microscope is not required, in fact, all our cases were performed using operative loupes. The light attachment provides superb visbility without the discomfort of having to wear a headlight. Thus far we have found no added risks or complications using this system. We are currently working on long-term analysis and follow-up to further evaluate this system's efficacy.

Fluoroscopy↗
PubMed2005

p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2.

The progression of normal cells from G2 into mitosis is stably blocked when their DNA is damaged. Tumor cells lacking p53 arrest only transiently in G2, but eventually enter mitosis. We show that an important component of the stable G2 arrest in normal cells is the transcriptional repression of more than 20 genes encoding proteins needed to enter into and progress through mitosis. Studies from a number of labs including our own have shown that, by inducing p53 and p21/WAF1, DNA damage can trigger RB-family-dependent transcriptional repression. Our studies reported here show that p130 and p107 play a key role in transcriptional repression of genes required for G2 and M in response to DNA damage. For plk1, repression is partially abrogated by loss of p130 and p107, and is completely abrogated by loss of all three RB-family proteins. Mouse cells lacking RB-family proteins do not accumulate with a 4N content of DNA when exposed to adriamycin, suggesting that all three RB-family proteins contribute to G2 arrest in response to DNA damage. Stable arrest in the presence of functional p53-to-RB signaling is probably due to the ability of cells to exit the cell cycle from G2, a conclusion supported by our observation that KI67, a marker of cell-cycle entry, is downregulated in both G1 and G2 in a p53-dependent manner.

Animals↗
PubMed2005

On the influence of soft tissue coverage in the determination of bone kinematics using skin markers.

Accurate measurement of underlying bone positions is important for the understanding of normal movement and function, as well as for addressing clinical musculoskeletal or post-injury problems. Non-invasive measurement techniques are limited by the analysis technique and movement of peripheral soft tissues that can introduce significant measurement errors in reproducing the kinematics of the underlying bones when using external skin markers. Reflective markers, skeletally mounted to the right hind limb of three Merino-mix sheep were measured simultaneously with markers attached to the skin of each segment, during repetitions of gait trials. The movement of the skin markers relative to the underlying bone positions was then assessed using the Point Cluster Technique (PCT), raw averaging and the Optimal Common Shape Technique (OCST), a new approach presented in this manuscript. Errors in the position of the proximal joint centre, predicted from the corresponding skin markers, were shown to be phasic and strongly associated with the amount soft tissue coverage, averaging 8.5 mm for the femur, 2.8 for the tibia and 2.0 for the metatarsus. Although the results show a better prediction of bone kinematics associated with the Optimal Common Shape Technique, these errors were large for all three assessment techniques and much greater than the differences between the various techniques. Whilst individual markers moved up to 4 mm from the optimal marker set configuration, average peak errors of up to 16, 5 and 3 mm (hip, knee and tibio-metatarsal joints respectively) were observed, suggesting that a large amount of kinematic noise is produced from the synchronous shifting of marker sets, potentially as a result of underlying muscle firing and the inertial effects of heel impact. Current techniques are therefore limited in their ability to determine the kinematics of underlying bones based on skin markers, particularly in segments with more pronounced soft tissue coverage.

Animals↗
PubMed2005

Kyphoplasty-augmented short-segment pedicle screw fixation of traumatic lumbar burst fractures: initial clinical experience and literature review.

OBJECT: Surgical intervention for thoracolumbar burst fractures is indicated for patients with neurological deficits and/or evidence of severe spinal instability. The goals of surgery are decompression, deformity correction, and stabilization. Nevertheless, the optimal surgical strategy to achieve these goals remains a subject of debate. Short-segment pedicle screw fixation is associated with a 20 to 50% incidence of pedicle screw failure and progressive spinal deformity. Initial biomechanical and clinical studies have shown that reinforcement of short-segment pedicle screw fixation with vertebroplasty improves spinal stability and decreases instrument failure rates. In this study, the authors describe their initial clinical experience with kyphoplasty used to augment short-segment pedicle screw fixation of traumatic lumbar burst fractures. METHODS: Five patients with traumatic burst fractures of the lumbar spine were included in this retrospective review of patients treated for this disorder at the University of California, San Diego and the University of California, San Francisco between 2002 and 2004. All patients underwent transpedicular kyphoplasty and short-segment pedicle screw fixation. The mean follow-up period was 10.6 months (range 6-18 months). All patients underwent short-segment pedicle screw fixation reinforced with polymethyl methacrylate kyphoplasty. The preoperative, postoperative, and follow-up plain x-ray films were evaluated. Radiographic analysis included measurements of kyphotic angulation, anterior vertebral body height, and evidence of bone fusion. Clinical evaluation was performed postoperatively and at follow-up review. CONCLUSIONS: Based on the authors' initial experience, kyphoplasty supplementation may improve the long-term integrity of short-segment pedicle screw constructs and allow for improved rates of fusion and better clinical outcomes in patients with traumatic lumbar burst fractures.

Adult↗
PubMed2005

Modelling molecular stability in the RNA world.

RNA secondary structure, stability and melting curves are calculated for a model of a possible ribozyme corresponding to the RNA directed RNA polymerase (ribopolymerase) required in the RNA world. From these calculations, rates of folding and hybridisation are estimated and used in a stochastic simulation of the dynamics of a population of ribopolymerase molecules. Two models are considered: one synthesising a conventional antiparallel reverse complementary transcript and one synthesising a parallel complementary transcript. It was found that the latter system can operate much more effective in the higher temperatures thought to prevail during the RNA world.

Base Sequence↗
PubMed2005

Surgical approach influences periprosthetic femoral bone density.

Our hypothesis was that the bone mineral density of the proximal femur is altered significantly by surgical approach. The change in long-term periprosthetic bone mineral density in relation to the alteration of the musculature after the anterolateral (Group A) and transgluteal approaches (Group B) has been compared. There were 35 hips (30 patients) in Group A and 47 hips (37 patients) in Group B. No significant differences were seen between groups with respect to age, gender, diaphyseal bone mineral density distribution, or average stem size in a Wilcoxon-Mann-Whitney test. Measurement of bone mineral density in femoral Gruen zones revealed a significant bone loss in Group B compared with Group A in the multivariate analysis, which was confirmed by univariate post hoc tests in Zones I, II, VI, and VII (multiple significance according to Bonferroni-Holm's procedure). The functional outcome, however, showed no significant differences between the two groups postoperatively. A potential reason for the bone mineral density shift might have been a redistribution of the musculoskeletal loading across the hip after a transgluteal, compared with an anterolateral, surgical approach. A difference in the muscular damage caused by the two surgical approaches seems to have a significant influence on the long-term bone loss.

Adult↗
PubMed2005

Alpha1-antitrypsin and neutrophil elastase imbalance and lung cancer risk.

OBJECTIVE: Imbalance between alpha(1)-antitrypsin and neutrophil elastase is an underlying cause of lung tissue damage that may create a favorable host environment for carcinogenesis. We conducted a case-control study to investigate whether genetic variations indicative of alpha(1)-antitrypsin deficiency (A1ATD) or an excess of neutrophil elastase modify lung cancer risk DESIGN: The case patients were 305 consecutively identified primary lung cancer patients, and the control subjects were 338 community residents. Protease inhibitor-1 (PI1), encoding alpha(1)-antitrypsin, was typed by an isoelectric focusing assay. Neutrophil elastase-2 (ELA2), encoding neutrophil elastase, was typed by two single-nucleotide polymorphism sites. Multivariable logistic regression models tested the independent and interactive effects of PI1, ELA2, tobacco smoke exposure, COPD, and family history of lung cancer RESULTS: Sex and ethnicity were comparable between case patients and control subjects, but case patients were more likely to be smokers, and to have a history of COPD, environmental tobacco smoke exposure, and a positive family history of lung cancer. Haplotype analysis indicated an overall strong association between the two ELA2 markers and lung cancer risk. Our best-fitting model showed significant and independent effects of the PI1-deficient allele (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4 to 3.0) and the ELA2 T-G haplotype (OR, 4.1; 95% CI, 1.9 to 8.9) on lung cancer risk, and an increased risk (OR, 2.6; 95% CI, 2.4 to 2.8) for individuals carrying both a PI1-deficient allele and a G-G haplotype CONCLUSIONS: Genotypes indicative of A1ATD and/or an excess of neutrophil elastase are significantly associated with lung cancer risk. Our findings may provide opportunities to better understand the mechanisms of lung cancer development and risk reduction.

Aged↗