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M Lord

Publications and source records attributed to M Lord.

At least 19 recordsLinked to original sources
PubMed2000

A study of in-shoe plantar shear in normals.

OBJECTIVE: To quantify features of in-shoe plantar shear in asymptomatic adult gait. DESIGN: In order to standardize footwear conditions and facilitate later comparison to patient groups, measurement is made in a group of adults walking freely in stock orthopaedic footwear. BACKGROUND: Better data on plantar shear is required to complement well-documented pressure data for an overall picture of plantar stress. METHODS: Measurements were made locally beneath the medial four metatarsal heads and heel using biaxial transducers mounted flush into an inlay. Pressure distribution was also measured. RESULTS: The shear data revealed common features in the shear pattern occurring at defined phases of gait, with good inter-step reliability. For the five sites of interest, these values ranged from 24 kPa to 70.4 kPa, and 31 kPa to 86.5 kPa for individuals wearing nylon hose or hose-free respectively. Maximum shear occurred more laterally than maximum pressure. CONCLUSIONS: Features of plantar shear were not always as expected; for example the forward thrust at push-off was not reflected in the anteroposterior shear stress. Because of the inter-subject variability, study of a larger group is indicated. RELEVANCE: Mechanical stress at the plantar interface between foot and shoe is of particular clinical relevance to the formation and management of ulcers in diabetic neuropathy. It is also of relevance to shoe and orthotic design for various foot pathologies. This study provides reliable data on the shear component of plantar stress for which, unlike the well-documented pressure component, there is only sparse data so far available.

Adult↗
PubMed2000

A study of in-shoe plantar shear in patients with diabetic neuropathy.

OBJECTIVE: To quantify in-shoe plantar shear in diabetic neuropathic feet. DESIGN: Plantar shear stresses are measured in a group of six patients with a history of diabetic neuropathic ulceration. BACKGROUND: Although elevated pressure between foot and shoe frequently found in diabetic neuropathic patients has been linked to a raised incidence of plantar ulceration, the shear component of stress at this interface is as yet unquantified. It is suggested that its effects may be equally damaging. METHODS: Measurements of shear were made locally beneath the medial four metatarsal heads and heel during unpaced gait in orthopaedic footwear, using a bi-axial magneto-resistive shear transducer. Similar methodology was previously employed on a group of asymptomatic adults, thereby allowing comparisons to be made. RESULTS: Overall the maximum shear stress for this patient group (73 kPa) was not significantly different to that in the asymptomatic group (87 kPa). However the patient group exhibited lower magnitudes of shear stress under the third/fourth metatarsal heads (average 51/39 vs. 86.5/71 kPa, respectively) and higher magnitudes under the first/second heads (73/64 vs. 35/31 kPa, respectively), indicating a medial shift. Step-to-step variability of maximum shear measured under the third metatarsal head showed an increase in the transverse component (coefficient of reliability 67% vs. 98%). CONCLUSIONS: Although the overall patterns of shear are broadly similar to the asymptomatic group, these pilot trials indicate a medial shift in shear loading under the forefoot coupled to increased step-to-step variability in the diabetic group. RelevanceMechanical stress at the plantar interface between foot and shoe is of particular clinical relevance to the formation and management of ulcers in diabetic neuropathy. Whereas the pressure component of stress is widely studied, the shear component is poorly described although it may be of equal importance.

Aged↗
PubMed1999

Replacement of vegetative sigmaA by sporulation-specific sigmaF as a component of the RNA polymerase holoenzyme in sporulating Bacillus subtilis.

Soon after asymmetric septation in sporulating Bacillus subtilis cells, sigmaF is liberated in the prespore from inhibition by SpoIIAB. To initiate transcription from its cognate promoters, sigmaF must compete with sigmaA, the housekeeping sigma factor in the predivisional cell, for binding to core RNA polymerase (E). To estimate the relative affinity of E for sigmaA and sigmaF, we made separate mixtures of E with each of the two sigma factors, allowed reconstitution of the holoenzyme, and measured the concentration of free E remaining in each mixture. The affinity of E for sigmaF was found to be about 25-fold lower than that for sigmaA. We used quantitative Western blotting to estimate the concentrations of E, sigmaA, and sigmaF in sporulating cells. The cellular concentrations of E and sigmaA were both about 7.5 microM, and neither changed significantly during the first 3 h of sporulation. The concentration of sigmaF was extremely low at the beginning of sporulation, but it rose rapidly to a peak after about 2 h. At its peak, the concentration of sigmaF was some twofold higher than that of sigmaA. This difference in concentration cannot adequately account for the replacement of sigmaA holoenzyme by sigmaF holoenzyme in the prespore, and it seems that some further mechanism-perhaps the synthesis or activation of an anti-sigmaA factor-must be responsible for this replacement.

Bacillus subtilis↗
PubMed1999

Plantar pressures are elevated in the neuroischemic and the neuropathic diabetic foot.

OBJECTIVE: Clinical observation has noted that diabetic neuropathic ulcers occur frequently on the plantar surface, whereas neuroischemic ulcers seem to occur often on the foot margins. The reason for this difference in the site of ulceration is unknown, but it may be related to differences in pressure loading. The aim of the study was to compare vertical in-shoe foot pressures measured during walking (using the F-SCAN system) in four groups of patients whose degree of neuropathy was measured by vibration perception threshold (VPT). RESEARCH DESIGN AND METHODS: Subjects included 14 neuroischemic diabetic patients (VPT 29.3 +/- 13.5 V) with history of ulceration on the margins of the foot, 18 patients with neuropathy alone (VPT 38.7 +/- 12.7 V) and previous history of ulceration on the plantar surface, 10 diabetic control patients (VPT 9.9 +/- 2.7 V), and 15 nondiabetic control subjects (VPT 7.0 +/- 0.5 V). RESULTS: When compared with the other three groups, neuroischemic patients had higher foot pressures when measured as mean peak pressures and highest peak pressures under four areas of the foot: medial and lateral forefoot, hallux, and heel. Furthermore, when measuring the maximum pressures developed at any point under the plantar surface, the neuroischemic patients also had the most elevated pressures (757.6 +/- 135.9 kPa), significantly higher than those found in the neuropathic group (482.8 +/- 68.6 kPa, P = 0.04) and in both diabetic control patients (310.2 +/- 34.7 kPa, P = 0.008) and nondiabetic controls subjects (365.1 +/- 49.8 kPa, P = 0.007). CONCLUSIONS: Despite having increased plantar pressures and a comparable degree of neuropatny, the neuroischemic patients did not have a history of ulceration on the plantar surface. These observations may have relevance to different mechanisms of ulcer formation in the neuroischemic and neuropathic foot.

Diabetic Angiopathies↗
PubMed1998

Developing and testing a system to improve the quality of heparin anticoagulation in patients with acute cardiac syndromes.

We have taken a stepwise approach to improving the dosing of continuous intravenous heparin in patients with acute coronary syndromes. Our primary objective was to use computer modeling to develop a nomogram for managing heparin therapy and to put in place a continuous quality monitoring system to evaluate the nomogram's effectiveness. We prospectively collected data on 41 patients with unstable angina or myocardial infarction who were treated with heparin. Their response to heparin was computer modeled and the dose to achieve an activated partial thromboplastin time (aPTT) ratio of 2.0 was established. This dose was regressed against all demographic characteristics to establish predictors of heparin dose (phase I). The regression formula was used prospectively in 110 patients to initiate the infusion rate of heparin and a bolus dose to achieve an aPTT ratio of 2.5. Subsequent dosage adjustments were achieved by computer modeling the patient's aPTT response (phase II). A nomogram was developed that simulated the decisions achieved using computer-assisted methods. This was retrospectively tested and then prospectively tested in 50 patients using nursing staff (phase IV). The nomogram was then made generally available (phase IV) and has been tested in an additional 310 patients. Phase I: Of the original 41 patients, 32% of the aPTT ratios were in the therapeutic range, 36% were supratherapeutic, and 32% were subtherapeutic after the first 24 hours. Phases II and III resulted in 85% of the aPTT ratios between 1.5 and 2.5 at 24 hours. Phase 4 had similar results in 310 patients. The use of computer-assisted or a computer-generated nomogram to adjust heparin therapy results in better control of heparin therapy than using standard methods.

Adult↗
PubMed1998

Differences in cytotoxicity of native and engineered RIPs can be used to assess their ability to reach the cytoplasm.

Ricin is a heterodimeric cytotoxin composed of RTB, a galactose binding lectin, and RTA, an enzymatic N-glycosidase. The toxin is endocytosed, and after intracellular routing, RTA is translocated to the cytoplasm where it inactivates ribosomes resulting in a loss of host cell protein synthesis and cell death. We show for the first time that the cytotoxicity against cultured T cells by several RTA mutants is directly proportional to the enzyme activity of RTA, suggesting this is a reliable system to measure translocation effects. Large discrepancies between cytotoxicity and enzyme action for a given pair of toxins are therefore attributable to differences in cell binding, uptake, or membrane translocation. Fluid phase uptake and cytotoxicity of isolated RTA are essentially identical to that of the single chain toxin PAP. This important finding suggests that RTA, and the A chain of class 2 RIPs in general, has not evolved special translocation signals to complement the increased target cell binding facilitated by RTB. Experiments with the lectin RCA and with ebulin suggest those toxins have diminished cytotoxicity probably mediated by comparative deficiencies in B chain binding. Addition of a KDEL sequence to RTA increases fluid phase uptake, consistent with the notion that transport to the ER is important for cytotoxicity. Fusion of MBP or GST to the amino terminus of RTA has little effect on enzyme action or cytotoxicity. This result is not altered by protease inhibitors, suggesting the fusion proteins are probably not cleaved prior to translocation of the toxic A chain and implying that the toxins can carry large passenger proteins into the cytoplasm, an observation with interesting potential for analytical and therapeutic chemistry.

Amino Acid Sequence↗
PubMed1998

Solution structure of SpoIIAA, a phosphorylatable component of the system that regulates transcription factor sigmaF of Bacillus subtilis.

The establishment of differential gene expression in sporulating Bacillus subtilis involves four protein components, one of which, SpoIIAA, undergoes phosphorylation and dephosphorylation. We have used NMR spectroscopy to determine the solution structure of the nonphosphorylated form of SpoIIAA. The structure shows a fold consisting of a four-stranded beta-sheet and four alpha-helices. Knowledge of the structure helps to account for the phenotype of several strains of B. subtilis that carry known spoIIAA mutations and should facilitate investigations of the conformational consequences of phosphorylation.

Amino Acid Sequence↗
PubMed1997

Spatial resolution in plantar pressure measurement.

Peaks of pressure under the foot are of significance to the understanding and limitation of damage to plantar tissues. At present, many of the pressure measuring systems use a matrix of discrete transducer cells which each register the average pressure over their surface, and whose dimensions are such that they limit the accurate representation of the true peak pressure. The spatial filtering effect is investigated in this paper by analytical deduction from a pedobarographic record of high spatial resolution. For a barefoot diabetic patient who presents sharp peaks of pressure in the metatarsal region, the effect of national cell dimensions is investigated through analysis of a typical record and shown to constitute a potentially significant error for cells of the dimensions of those in common use. The average pressure read from a transducer of area 100 mm2 may be of the order of 60-70% of the true peak in barefoot standing, although this depends on the sharpness of the peaks. Errors are decreased when the more even in-shoe pressure distribution is considered.

Biomedical Engineering↗
PubMed1997

Contribution of partner switching and SpoIIAA cycling to regulation of sigmaF activity in sporulating Bacillus subtilis.

sigmaF, the first compartment-specific transcription factor in sporulating Bacillus subtilis, is negatively regulated by an anti-sigma factor, SpoIIAB. SpoIIAB has an alternative binding partner, SpoIIAA. To see whether (as has been proposed) SpoIIAB's binding preference for SpoIIAA or sigmaF depends on the nature of the adenine nucleotide present, we used surface plasmon resonance to measure the dissociation constants of the three complexes SpoIIAA-SpoIIAB-ADP, sigmaF-SpoIIAB-ADP, and sigmaF-SpoIIAB-ATP. The results suggested that SpoIIAB's choice of binding partner is unlikely to depend on the ATP/ADP ratio in the cell. The intracellular concentrations of sigmaF, SpoIIAB, SpoIIAA, and SpoIIAA-phosphate (SpoIIAA-P) were measured by quantitative immunoblotting between 0 and 3 h after the beginning of sporulation (t0 to t3). sigmaF and SpoIIAB were barely detectable at t0, but their concentrations increased in parallel to reach maxima at about t1.5. SpoIIAA-P increased steadily to a maximum at t3, but nonphosphorylated SpoIIAA was detectable only from t1.5, reached a maximum at t2.5, and then declined. Kinetic studies of the phosphorylation of SpoIIAA catalyzed by SpoIIAB suggested that the reaction was limited by a very slow release of one of the products (SpoIIAA-P or ADP) from SpoIIAB, with a turnover of about once per 20 min. This remarkable kinetic property provides an unexpected mechanism for the regulation of sigmaF. We propose that when SpoIIE (which dephosphorylates SpoIIAA-P) is active at the same time as SpoIIAB, SpoIIAA cycles repeatedly between the phosphorylated and nonphosphorylated forms. This cycling sequesters SpoIIAB in a long-lived complex and prevents it from inhibiting sigmaF.

Bacillus subtilis↗
PubMed1996

Control of the cell-specificity of sigma F activity in Bacillus subtilis.

Sporulation in Bacillus subtilis is a simple developmental system involving the differentiation of two cell types that are formed by an asymmetric cell division. Major changes in the pattern of transcription during sporulation are brought about by the synthesis of new sigma factors (sigma), which are subunits of RNA polymerase that determine promoter specificity. Transcription in the smaller prespore cell type is initiated by a sigma factor called sigma F, the activity of which is subject to tight spatial and temporal control. It is negatively regulated by an anti-sigma factor, SpoIIAB, which is in turn controlled by an anti-anti-sigma factor, SpoIIAA. SpoIIAA and SpoIIAB participate in two contrasting reactions in vitro. In the presence of ATP, the proteins interact transiently and SpoIIAA is inactivated by phosphorylation on a specific serine residue; SpoIIAA then remains free to inhibit sigma F. In the presence of ADP, SpoIIAA binds tightly to SpoIIAB, and sigma F is set free. Release of sigma F activity in vivo might thus be effected by a prespore-specific reduction in the ATP/ADP ratio. Genetic experiments have implicated a fourth protein, called SpoIIE, in this system. It now appears that SpoIIE has two important and independent functions in the establishment of the prespore-specific transcription by sigma F. First it regulates sigma F activity, probably acting as a phosphatase to regenerate the active, non-phosphorylated form of SpoIIAA. Second it controls the formation of the septum that generates the prespore compartment. Combination of these two functions in a single polypeptide may provide a means of coupling gene expression with morphogenesis.

Amino Acid Sequence↗
PubMed1996

New product development processes within the UK medical device industry.

This paper reports on the findings of an extensive survey investigating practising design engineers' perceptions of new product development within the UK medical device industry. The design activity recorded was predominantly the small-scale development of low volume products. Explicit formal procedures were rarely used in these small-scale developments of low volume products. Specific organizational and design process issues are identified by the respondents as key requirements for the success of the new product development process.

Commerce↗
PubMed1996

Establishing differential gene expression in sporulating Bacillus subtilis: phosphorylation of SpoIIAA (anti-anti-sigmaF) alters its conformation and prevents formation of a SpoIIAA/SpoIIAB/ADP complex.

Sigma-factor F (sigmaF) is a key transcription factor that initiates prespore development in Bacillus subtilis. Its activity is controlled by an anti-sigma factor, SpoIIAB, which is also a protein kinase that phosphorylates the anti-anti-sigma factor SpoIIAA. We have examined our earlier prediction that SpoIIAA must undergo a major change in its properties when phosphorylated. Upon gel filtration in the presence of ADP, SpoIIAA-P was eluted from a Superdex column much later than SpoIIAB, whereas SpoIIAA was coeluted with SpoIIAB, indicating the formation of a protein/protein complex. The complex contained ADP, and had two monomers of SpoIIAA to each SpoIIAB dimer. Its dissociation constant was 13 mu M. Gel permeation on high-performance liquid chromatography (HPLC) suggested an apparent molecular mass for SpoIIAA-P which was much higher (23.5 kDa) than that of SpoIIAA (15.8 kDa), but Ferguson plots showed that SpoIIAA-P was not a phosphorylated dimer of SpoIIAA. Our tentative conclusion, that SpoIIAA and SpoIIAA-P differ markedly in conformation, was confirmed by the results of partial digestion with chymotrypsin.

Adenosine Diphosphate↗
PubMed1996

Open anterior dislocation of the shoulder.

Open dislocation of the shoulder is a rare injury. We report the case of an open shoulder dislocation in a 15-year-old boy. After 15 months his pain was mild and function fair, but radiographs revealed severe destruction of the humeral head though to be secondary to avascular necrosis. Other reported cases of this injury are discussed.

Accidents, Occupational↗