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Biomedical subjects

D R Williams

Publications and source records attributed to D R Williams.

At least 19 recordsLinked to original sources
PubMed2006

Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau.

The majority of neurodegenerative diseases are characterized by the deposition of insoluble protein in cells of the neuromuscular system. Advances in molecular neuropathology have allowed a classification system of neurodegenerative diseases based on this protein accumulation. Microtubule-associated tau is one protein that has important functions in healthy neurons, but forms insoluble deposits in diseases now known collectively as tauopathies. Tauopathies encompass more than 20 clinicopathological entities, including Alzheimer's disease, the most common tauopathy, progressive supranuclear palsy, Pick's disease, corticobasal degeneration and post-encephalitic parkinsonism. There are important clinical, pathological, biochemical and genetic similarities in the range of these diseases and they have helped to advance our understanding of the aetiological factors that initiate neurodegeneration and tau accumulation. This review examines the important clinical features of the most prevalent tauopathies and the molecular and pathological features that underpin the classification system.

Animals↗
PubMed2006

Predictors of falls and fractures in bradykinetic rigid syndromes: a retrospective study.

BACKGROUND: Falls and fractures contribute to morbidity and mortality in bradykinetic rigid syndromes. METHODS: The authors performed a retrospective case notes review at the Queen Square Brain Bank for Neurological Disorders and systematically explored the relation between clinical features and falls and fractures in 782 pathologically diagnosed cases (474 with Parkinson's disease (PD); 127 progressive supranuclear palsy (PSP); 91 multiple system atrophy (MSA); 46 dementia with Lewy bodies (DLB); 27 vascular parkinsonism; nine Alzheimer's disease; eight corticobasal degeneration). RESULTS: Falls were recorded in 606 (77.5%) and fractures in 134 (17.1%). In PD, female gender, symmetrical onset, postural instability, and autonomic instability all independently predicted time to first fall. In PD, PSP, and MSA latency to first fall was shortest in those with older age of onset of disease. Median latency from disease onset to first fall was shortest in Richardson's syndrome (12 months), MSA (42), and PSP-parkinsonism (47), and longest in PD (108). In all patients fractures of the hip were more than twice as common as wrist and forearm fractures. Fractures of the skull, ribs, and vertebrae occurred more frequently in PSP than in other diseases. CONCLUSION: Measures to prevent the morbidity associated with falls and fractures in bradykinetic rigid syndromes may be best directed at patients with the risk factors identified in this study.

Accidental Falls↗
PubMed2005

A new dominant distal myopathy affecting posterior leg and anterior upper limb muscles.

OBJECTIVE: To report a dominant, slowly progressive early onset distal myopathy with sparing of the tibialis anterior. METHODS: Twelve affected and two possibly affected members from an Australian kindred were examined and investigated by EMG, imaging studies, histopathology, and genetic analysis. RESULTS: Affected patients had a slowly progressive condition with symmetric, distal weakness and wasting of the anterior upper and posterior lower limbs, with sparing of tibialis anterior, even in advanced disease. All patients remained ambulant and there was no evidence of cardiac or respiratory muscle involvement. Serum creatine kinase levels were either normal or mildly elevated. Imaging studies showed widespread involvement of the posterior and lateral leg compartments. Proximal muscles were radiologically abnormal only in advanced disease. Muscles that were mildly affected clinically appeared normal on imaging. EMG in nine patients showed widespread myopathic changes. Muscle histopathology in four patients showed either end stage muscle or nonspecific myopathic findings without inflammation or vacuoles. Microsatellite markers for distal myopathy loci were analyzed and all known distal myopathy phenotype genes and linkage regions were formally excluded by multipoint analysis. CONCLUSIONS: The affected patients in this kindred display a clinically distinct myopathy, with selective involvement of posterior lower and anterior upper limb muscles. The genetic analysis suggests the existence of one more distal myopathy locus.

Adolescent↗
PubMed2005

Fourier transform infrared imaging of human hair with a high spatial resolution without the use of a synchrotron.

The cross-section of a human hair has been imaged for the first time using the micro attenuated total reflection (ATR) Fourier transformed infrared (FT-IR) method in combination with a focal plane array (FPA) detector. A rigorous approach was applied to determine the spatial resolution, namely, measuring the distance over which the band absorbance changes from 95 to 5% of the maximum absorbance when passing through a sharp interface. The measured value for IR transmission was approximately 16 microm, while the value obtained using ATR imaging was approximately 5 microm. The enhanced spatial resolution achieved by this method allows the medulla of the hair (approximately 8 microm in diameter) to be imaged clearly without the need for a synchrotron source. The spatial resolution of transmission and ATR imaging is compared, and advantages of ATR imaging are discussed.

Amides↗
PubMed2004

A reappraisal of the incremental packing technique for light cured composite resins.

The cuspal flexure caused by a direct placement composite resin was measured using a technique that did not interfere with cuspal movement. Twenty upper premolar teeth with mesial-occlusal-distal (MOD) cavity preparations were restored using a posterior composite resin. Ten teeth were restored using a bulk packing technique and 10 were restored using three 'U' shaped bucco-lingual increments. Total cuspal movement was measured 1 h following the initiation of curing. Bulk placement of the composite resin produced slightly more cuspal movement (12.5 microm) compared with the incremental placement of composite (11.3 microm). This difference was not statistically significant. The technique of incremental packing to reduce cuspal flexure is therefore questioned.

Bicuspid↗
PubMed2003

Intravenous lignocaine (lidocaine) infusion for the treatment of chronic daily headache with substantial medication overuse.

Patients with chronic daily headache with medication overuse are difficult to treat, especially when the doses of analgesia are substantial. We have previously shown that intravenous lignocaine (lidocaine) infusion is useful in maintaining pain control while the offending analgesic agent is withdrawn in these patients. The published data on long-term efficacy of this treatment is limited. We undertook a retrospective survey of 71 consecutive patients admitted for lignocaine infusion (mean 8.7 days) for treatment of chronic daily headache, with substantial analgesic abuse. Ninety percent of patients had a history of migraine headaches. In 80% of patients codeine was the predominant agent implicated in the analgesic rebound headaches (mean 1053 mg/week) and 24% used ergotamine-containing medications (mean 16 mg/week). Thirty-one percent frequently used injected narcotics. At completion 90% reported that their daily headache was absent or improved, and the analgesic agent was withdrawn successfully in 97%. At six month follow-up, 70% of patients reported that their daily headache was absent or improved and 72% of patients remained free of the offending analgesic agent. Intravenous lignocaine is a useful treatment in the management of chronic daily headache with substantial medication overuse. The benefits of the program last for at least six months.

Adolescent↗
PubMed2001

Total synthesis of cystothiazoles A and C.

An efficient pathway culminating in the enantiocontrolled preparation of cystothiazoles A and C has been described. The cystothiazoles demonstrate potent antifungal activity and function as novel inhibitors of mitochondrial oxidation at a specific site on the cytochrome bc(1) complex. These studies outline a general and flexible plan that can be readily adapted for the synthesis of a variety of related five-membered heterocyclic systems and for biological investigations of structure-activity relationships. The core [2,4']bisthiazole component 8 was prepared in six steps, and the use of the Horner-Emmons olefination to yield the alpha,beta-unsaturated ester 10 set the stage for an asymmetric Evans aldol process, which established the required C(4)/C(5) stereochemistry. Finally the cystothiazoles A and C were prepared via a stereocontrolled O-alkylation of the precursor beta-keto esters 22a and 22b.

Deltaproteobacteria↗
PubMed2001

Specific ion effects: why DLVO theory fails for biology and colloid systems.

The classical Derjaguin-Landau-Verwey-Overbeek theory that underpins colloid and surface science is shown to be flawed, especially at biological salt concentrations. This is in part because the dispersion forces acting on the ions are ignored. When these are included properly very different results are obtained. These results have substantial implications for biological and for ordinary colloid systems at moderate salt concentrations.

Algorithms↗
PubMed2001

Total synthesis of (-)-stemospironine.

[structure: see text]. A stereocontrolled total synthesis of the polycyclic Stemona alkaloid, (-)-stemospironine (1) has been achieved. Key transformations include the use of a Staudinger reaction leading to the aza-Wittig ring closure of the perhydroazepine system. Formation of the vicinal pyrrolidine butyrolactone is described via the stereoselective intramolecular capture of an intermediate aziridinium salt.

Alkaloids↗
PubMed2001

Shear-dependent boundary slip in an aqueous Newtonian liquid.

We report direct measurements of hydrodynamic drainage forces, which show clear evidence of boundary slip in a Newtonian liquid. The degree of boundary slip is found to be a function of the liquid viscosity and the shear rate, as characterized by the slip length, and is up to approximately 20 nm. This has implications for confined biological systems, the permeability of microporous media, and for the lubrication of nanomachines, and will be important in the microcontrol of liquid flow. We also show that current theories of slip do not adequately describe the experimental data.

Journal Article↗
PubMed2001

Total synthesis of (-)-ratjadone.

[reaction in text] A convergent asymmetric synthesis of (-)-ratjadone (1) has been achieved, confirming the assignments of stereochemistry for the naturally occurring antifungal metabolite.

Antifungal Agents↗
PubMed2001

The use of inverse phase gas chromatography to study the change of surface energy of amorphous lactose as a function of relative humidity and the processes of collapse and crystallisation.

The purpose of this study was to assess the effect of relative humidity (RH) on the surface energy of amorphous lactose. Two samples of amorphous lactose were investigated; a spray dried 100% amorphous material and a ball milled sample of crystalline lactose. The milled sample had less than 1% amorphous content by mass, but on investigation at 0% RH, yielded surface energies comparable to those obtained from the 100% amorphous material, indicating that the surface was amorphous. The effect of increasing humidity was to reduce the dispersive surface energy of the two samples from 36.0 +/- 0.14 and 41.6 +/- 1.4 mJ m(-2) at 0% RH for the spray dried and milled samples respectively, to a value comparable to that obtained for the crystalline alpha-lactose monohydrate of 31.3 +/- 0.41 mJ m(-2). The change in surface energy due to water sorption was only reversible up to 20% RH; after exposure to higher RH values subsequent drying did not result in a return to the original surface energy of the amorphous form. This shows that the surface is reorganising as the glass transition temperature (Tg) is reduced, even though the sample has not collapsed or crystallised. It was possible to follow the collapse behaviour in the column with ease, using a number of different methods.

Absorption↗
PubMed2001

Toroidal condensates of semiflexible polymers in poor solvents: adsorption, stretching, and compression.

When a semiflexible polymer chain is placed in a poor solvent, or in the presence of condensing agents, a toroidal condensate can result. In typical experiments, these condensates are adsorbed to surfaces. Here we examine the changes that can occur when a toroid is adsorbed. We then examine the behavior of a toroid when stretched and identify two regimes: a weak stretching regime where the toroid deforms from a circle to an ellipse, and a strong stretching regime where a tether is pulled from the toroid. In the weak stretching regime, the force increases linearly with separation whereas in the strong stretching regime, the applied force is a constant. We then look at the case of a toroid compressed in the plane of the toroid. In this case the form of the force law depends on how strongly the toroid wets the surfaces. In general, an inverse square force law is found.

Biophysical Phenomena↗
PubMed2001

Characterization and use of a digital light projector for vision research.

For creating stimuli in the laboratory, digital light projection (DLP) technology has the potential to overcome the low output luminance, lack of pixel independence, and limited chromaticity gamut of the cathode ray tube (CRT). We built a DLP-based stimulator for projecting patterns on the in vitro primate retina. The DLP produces high light levels and has good contrast. Spatial performance was similar to that of a CRT. Temporal performance was limited by the refresh rate (63 Hz). The chromatic gamut was modestly larger than that of a CRT although the primary spectra varied to a small degree with light output and numerical aperture.

Analog-Digital Conversion↗
PubMed2001

Packing arrangement of the three cone classes in primate retina.

We describe a detailed analysis of the spatial arrangement of L, M and S cones in the living eyes of two humans and one monkey. We analyze the cone mosaics near 1 degrees eccentricity using statistical methods that characterize the arrangement of each type of cone in the mosaic of photoreceptors. In all eyes, the M and L cones are arranged randomly. This gives rise to patches containing cones of a single type. In human, but not in monkey, the arrangement of S-cones cannot be distinguished from random.

Animals↗
PubMed2001

Socioeconomic disparities in health change in a longitudinal study of US adults: the role of health-risk behaviors.

This study investigated the hypothesis that socioeconomic differences in health status change can largely be explained by the higher prevalence of individual health-risk behaviors among those of lower socioeconomic position. Data were from the Americans' Changing Lives study, a longitudinal survey of 3,617 adults representative of the US non-institutionalized population in 1986. The authors examined associations between income and education in 1986, and physical functioning and self-rated health in 1994, adjusted for baseline health status, using a multinomial logistic regression framework that considered mortality and survey nonresponse as competing risks. Covariates included age, sex, race, cigarette smoking, alcohol consumption, physical activity, and Body Mass Index. Both income and education were strong predictors of poor health outcomes. The four health-risk behaviors under study statistically explained only a modest portion of the socioeconomic differences in health at follow-up. For example, after adjustment for baseline health status, those in the lowest income group at baseline had odds of moderate/severe functional impairment in 1994 of 2.11 (95% C.I.: 1.40, 3.20) in an unadjusted model and 1.89 (95% C.I.: 1.23, 2.89) in a model adjusted for health-risk behaviors. The results suggest that the higher prevalence of major health-risk behaviors among those in lower socioeconomic strata is not the dominant mediating mechanism that can explain socioeconomic disparities in health status among US adults.

Adult↗