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Biomedical subjects

S H White

Publications and source records attributed to S H White.

At least 19 recordsLinked to original sources
PubMed2006

Mortality and toxin bioaccumulation in Bufo marinus following exposure to Cylindrospermopsis raciborskii cell extracts and live cultures.

Cylindrospermopsis raciborskii is a cyanobacterium responsible for the production of the toxin, cylindrospermopsin (CYN). Tadpoles of the cane toad Bufo marinus were exposed to freeze-thawed whole cell extracts or live cultures of C. raciborskii containing maximum CYN concentrations of 400 microg L-1 or 232 microg L-1, respectively. Exposure to live culture treatment solutions resulted in up to 66% mortality of B. marinus, whereas tadpoles exposed to whole cell extracts containing similar toxin concentrations survived. Decreases in relative growth rates and time spent for swimming were recorded from tadpoles during both types of exposure regimes. Bioconcentration of CYN was not evident following exposure to whole cell extracts containing extracellular toxin. In contrast exposure to live cultures, which contained cell-bound toxin, resulted in maximum average tissue concentrations of 895 microg free-CYN kg-1 fresh weight. This is the first investigation of C. raciborskii exposure effects and toxin bioaccumulation in the developmental stages of an amphibian.

Alkaloids↗
PubMed2006

Minimally invasive Oxford medial unicompartmental knee arthroplasty. A note of caution!

We present the peak outcome results of the Oxford medial unicompartmental arthroplasty through a minimally invasive surgical incision. This prospective study included 78 Oxford medial unicompartmental knee replacements in 68 patients. At the 2 year review the patients achieved a mean Oxford Knee Score of 38.3. This was not significantly different to the 2 year results of the phase 2 Oxford knee carried out using a standard parapatellar approach when patients achieved a mean OKS of 36.0. Four unicompartmental knee replacements required revision for unexplained pain, deep infection, aseptic loosening and bearing dislocation. Minimally invasive joint replacement is attractive to both patients and surgeons, but is technically demanding with complications inherent to limited access.

Adult↗
PubMed2006

Influence of intracellular toxin concentrations on cylindrospermopsin bioaccumulation in a freshwater gastropod (Melanoides tuberculata).

Scant information is available regarding the bioaccumulation of cylindrospermopsin (CYN) in aquatic organisms, particularly in invertebrates. This study examined toxin bioconcentration and bioaccumulation in the aquatic snail, Melanoides tuberculata, following exposure to freeze-thawed whole cell extracts and a live Cylindrospermopsis raciborskii culture containing CYN. Both bioconcentration and bioaccumulation were evident, but exposure to toxin in the freeze-thawed solutions resulted in minor tissue contamination compared with that resulting from live C. raciborskii exposure. Thus, whilst CYN uptake resulted from both extracellular and intracellular exposures, the availability of intracellular toxin was critical in affecting tissue CYN values. M. tuberculata did not bioconcentrate CYN into the shell. Bioaccumulation of the analog deoxy-CYN was also recorded. Knowledge of intracellular toxin concentrations may be critical in evaluating the bioaccumulation, ecological and human health risks associated with contaminated systems.

Alkaloids↗
PubMed2006

The effect of preoperative symptom severity on functional outcome of total knee replacement--patients with the lowest preoperative scores achieve the lowest marks.

To determine if the functional outcome of total knee replacement (TKR) was affected by the level of preoperative symptom severity, the association between preoperative Oxford Knee Scores (OKS), and 2 year OKS, American Knee Society clinical and function scores (AKSS) was assessed. Data were prospectively collected on 45 cases who had single joint osteoarthritis and no other comorbidities. We have specifically focused on patients with single knee involvement to remove the effect of multiple joint involvement and comorbidities on the OKS. The mean preoperative OKS was 21.4, postoperative OKS 40.0 and postoperative ROM 117 degrees. The postoperative mean AKSS was 86.7 and mean function score was 85.0. The 'usual pain' and 'limp' components of the OKS had the greatest rises and the 'kneel' component had the least improvement. Rather than all patients achieving uniform results post-TKR, patients with more severe symptoms achieved poorer absolute outcomes. The Spearman correlation coefficient between pre- and postoperative OKS was r = 0.4 (p = 0.006). Although the results suggest that waiting too long before intervention compromises the final outcome, a correlation of 0.4 is not strong enough to necessitate change in current practice.

Activities of Daily Living↗
PubMed2005

Do protein-lipid interactions determine the recognition of transmembrane helices at the ER translocon?

Membrane-protein integration, folding and assembly processes in vivo depend on complex targeting, translocation, chaperoning, and sorting machineries that somehow read the 'molecular code' built into the nascent polypeptide, ultimately producing a properly folded protein integrated into the correct target membrane. Although the main molecular constituents and the basic mechanistic principles of many of these machines are known in outline, the codes remain poorly defined and there is little quantitative information on how protein sequence affects the final structure of membrane proteins. By carefully designing model protein constructs, we have derived the first true biological hydrophobicity scale and have been able to get a first impression of how the position of a given type of residue within a transmembrane segment affects its ability to promote membrane insertion.

Computer Simulation↗
PubMed2003

Analysis of the Leeds-Keio ligament for extensor mechanism repair: favourable mechanical and functional outcome.

Many techniques have been described for the challenging problem of extensor mechanism rupture, including the use of synthetic grafts. In 1994 Fujikawa et al. [J. Bone Surg. 1994:76B:200-203] reported excellent results using the Leeds-Keio polyester ligament. Patients were mobilised early, had few post operative complications and minimal extensor lag. This is the first independent assessment of this technique using both subjective and objective analysis of outcome. We reviewed 11 patients (12 knees) whose extensor mechanisms were repaired as described in the original paper. At a mean of 3 years after surgery there were no infections and no re-ruptures. Good functional recovery was observed with a mean Tegner activity score of 1.7, Lysholm score of 66 and Irrgang score of 58%. Indeed, 80% of working patients returned to their former employment. However, objective tests showed peak extensor torque recovered to only half normal strength. We conclude the results of this technique of repair compare favourably with other described techniques especially in complex cases.

Adult↗
PubMed2003

Operating on patients wearing personal identity devices: a report of two cases.

We report on two patients who have recently required emergency surgery and who were wearing personal identity devices at the time of presentation. The devices bear a telephone number and a message stating that, if found, the management company should be informed of the whereabouts of their owner. We discuss the issues relating to the disclosure of information to a third party in this situation and whether there is any legal obligation to do so. The conclusion of a review of the relevant literature is that the only reason to divulge information to a third party would be if a patient posed a serious risk of death or serious harm to another party. In the majority of foreseeable circumstances, this would not be the case.

Accidents, Traffic↗
PubMed2001

Energetics, stability, and prediction of transmembrane helices.

We show that the peptide backbone of an alpha-helix places a severe thermodynamic constraint on transmembrane (TM) stability. Neglect of this constraint by commonly used hydrophobicity scales underlies the notorious uncertainty of TM helix prediction by sliding-window hydropathy plots of membrane protein (MP) amino acid sequences. We find that an experiment-based whole-residue hydropathy scale (WW scale), which includes the backbone constraint, identifies TM helices of membrane proteins with an accuracy greater than 99 %. Furthermore, it correctly predicts the minimum hydrophobicity required for stable single-helix TM insertion observed in Escherichia coli. In order to improve membrane protein topology prediction further, we introduce the augmented WW (aWW) scale, which accounts for the energetics of salt-bridge formation. An important issue for genomic analysis is the ability of the hydropathy plot method to distinguish membrane from soluble proteins. We find that the method falsely predicts 17 to 43 % of a set of soluble proteins to be MPs, depending upon the hydropathy scale used.

Bacteriorhodopsins↗
PubMed2001

'Detergent-like' permeabilization of anionic lipid vesicles by melittin.

Melittin (MLT), the 26-residue toxic peptide from the European honeybee Apis mellifera, is widely used for studying the principles of membrane permeabilization by antimicrobial and other host-defense peptides. A striking property of MLT is that its ability to permeabilize zwitterionic phospholipid vesicles is dramatically reduced upon the addition of anionic lipids. Because the mechanism of permeabilization may be fundamentally different for the two types of lipids, we examined MLT-induced release of entrapped fluorescent dextran markers of two different molecular masses (4 and 50 kDa) from anionic palmitoyloleoylphosphatidylglycerol (POPG) vesicles. Unlike release from palmitoyloleoylphosphatidylcholine (POPC) vesicles, which is highly selective for the 4 kDa marker, implying release through pores of about 25 A diameter [Ladokhin et al., Biophys. J. 72 (1997) 1762], release from POPG vesicles was found to be non-selective, i.e., 'detergent-like'. Oriented circular dichroism measurements of MLT in oriented POPG and POPC multilayers disclosed that alpha-helical MLT can be induced to adopt a transbilayer orientation in POPC multilayers, but not in POPG multilayers. The apparent inhibition of MLT permeabilization by anionic membranes may thus be due to suppression of translocation ability.

Circular Dichroism↗
PubMed2001

Protein chemistry at membrane interfaces: non-additivity of electrostatic and hydrophobic interactions.

Non-specific binding of proteins and peptides to charged membrane interfaces depends upon the combined contributions of hydrophobic (DeltaG(HPhi)) and electrostatic (DeltaG(ES)) free energies. If these are simply additive, then the observed free energy of binding (DeltaG(obs)) will be given by DeltaG(obs)=DeltaG(HPhi)+DeltaG(ES), where DeltaG(HPhi)=-sigma(NP)A(NP) and DeltaG(ES)=zFphi. In these expressions, A(NP) is the non-polar accessible area, sigma(NP) the non-polar solvation parameter, z the formal peptide valence, F the Faraday constant, and phi the membrane surface potential. But several lines of evidence suggest that hydrophobic and electrostatic binding free energies of proteins at membrane interfaces, such as those associated with cell signaling, are not simply additive. In order to explore this issue systematically, we have determined the interfacial partitioning free energies of variants of indolicidin, a cationic proline-rich antimicrobial peptide. The synthesized variants of the 13 residue peptide covered a wide range of hydrophobic free energies, which allowed us to examine the effect of hydrophobicity on electrostatic binding to membranes formed from mixtures of neutral and anionic lipids. Although DeltaG(obs) was always a linear function of DeltaG(HPhi), the slope depended upon anionic lipid content: the slope was 1.0 for pure, zwitterionic phosphocholine bilayers and 0.3 for pure phosphoglycerol membranes. DeltaG(obs) also varied linearly with surface potential, but the slope was smaller than the expected value, zF. As observed by others, this suggests an effective peptide valence z(eff) that is smaller than the formal valence z. Because of our systematic approach, we were able to establish a useful rule-of-thumb: z(eff) is reduced relative to z by about 20 % for each 3 kcal mol(-1) (1 kcal=4.184 kJ) favorable increase in DeltaG(HPhi). For neutral phosphocholine interfaces, we found that DeltaG(obs) could be predicted with remarkable accuracy using the Wimley-White experiment-based interfacial hydrophobicity scale.

Amino Acid Sequence↗
PubMed2001

Structure, location, and lipid perturbations of melittin at the membrane interface.

Melittin is arguably the most widely studied amphipathic, membrane-lytic alpha-helical peptide. Although several lines of evidence suggest an interfacial membrane location at low concentrations, melittin's exact position and depth of penetration into the hydrocarbon core are unknown. Furthermore, the structural basis for its lytic action remains largely a matter of conjecture. Using a novel x-ray absolute-scale refinement method, we have now determined the location, orientation, and likely conformation of monomeric melittin in oriented phosphocholine lipid multilayers. Its helical axis is aligned parallel to the bilayer plane at the depth of the glycerol groups, but its average conformation differs from the crystallographic structure. As observed earlier for another amphipathic alpha-helical peptide, the lipid perturbations induced by melittin are remarkably modest. Small bilayer perturbations thus appear to be a general feature of amphipathic helices at low concentrations. In contrast, a dimeric form of melittin causes larger structural perturbations under otherwise identical conditions. These results provide direct structural evidence that self-association of amphipathic helices may be the crucial initial step toward membrane lysis.

Animals↗
PubMed2001

Magnetic resonance imaging assessment for unicompartmental knee replacement: a limited role.

The purpose of this study was to see if MRI has a role in pre-operative assessment of patients for unicompartmental knee replacement. Until now, surgeons have been unable to predict whether a patient is suitable until the operation itself when the anterior cruciate ligament is inspected. We found that 33% of patients with anteromedial osteoarthritis had a degenerate anterior cruciate ligament according to magnetic resonance imaging, compared to only 13% on surgical inspection. We conclude that MRI is too sensitive to changes of the anterior cruciate ligament to be of much practical value.

Anterior Cruciate Ligament↗
PubMed2001

Perceptions of outcomes after unicompartmental and total knee replacements.

An independent measurement of the quality of outcome of 31 consecutive Oxford medial unicompartmental knee replacements in 28 patients and 130 total knee replacements in 104 patients performed between 1993 and 1997 is reported. The indications for surgery were anteromedial osteoarthritis for unicompartmental replacement and more extensive osteoarthritis for total knee replacement. All patients were treated by one surgeon. As a validated outcome measure of knee function, the Oxford 12-item knee questionnaire showed identical outcome in both groups with a mean score of 36.5 (maximum possible, 48). Neither the pain nor the functional outcomes were significantly different, although patients receiving unicompartmental replacement were better able to descend stairs. Two patients needed revision surgery in the unicompartmental replacement group compared with only one patient in the total knee replacement group. The femoral component of two unicompartmental replacements showed radiologic signs of loosening. The tibial component of one total knee replacement appeared loose, but the patient had no symptoms. In comparison with total knee replacement, implantation of meniscal bearing unicompartmental replacement technically is demanding and unforgiving. However, revision of a failed Oxford unicompartmental replacement is easier than revision of a failed total knee replacement, and the authors recommend this device for younger patients in whom one could expect a total knee replacement to fail within their lifetime.

Activities of Daily Living↗
PubMed2001

MPtopo: A database of membrane protein topology.

The reliability of the transmembrane (TM) sequence assignments for membrane proteins (MPs) in standard sequence databases is uncertain because the vast majority are based on hydropathy plots. A database of MPs with dependable assignments is necessary for developing new computational tools for the prediction of MP structure. We have therefore created MPtopo, a database of MPs whose topologies have been verified experimentally by means of crystallography, gene fusion, and other methods. Tests using MPtopo strongly validated four existing MP topology-prediction algorithms. MPtopo is freely available over the internet and can be queried by means of an SQL-based search engine.

Algorithms↗