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Biomedical subjects

M Stone

Publications and source records attributed to M Stone.

At least 19 recordsLinked to original sources
PubMed2003

Floc morphology and size distributions of cohesive sediment in steady-state flow.

Fractal dimensions of particle populations of cohesive sediment were examined during deposition experiments in an annular flume at four conditions of steady-state flow (0.058, 0.123, 0.212 and 0.323Pa). Light microscopy and an image analysis system were used to determine area, longest axis and perimeter of suspended solids. Four fractal dimensions (D, D(1), D(2), D(k)) were calculated from the slopes of regression lines of the relevant variables on double log plots. The fractal dimension D, which relates the projected area (A) to the perimeter (P) of the particle (P proportional, variant A(D/2)), increased from 1.25+/-0.005 at a shear stress of 0.058Pa to a maximum of 1.36+/-0.003 at 0.121Pa then decreased to 1.34+/-0.001 at 0.323Pa. The change in D indicated that particle boundaries became more convoluted and the shape of larger particles was more irregular at higher levels of shear stress. At the highest shear stress, the observed decrease in D resulted from floc breakage due to increased particle collisions. The fractal dimension D(1), which relates the longest axis (l) to the perimeter of the particle (P proportional to l(D1)), increased from 1.00+/-0.006 at a shear stress of 0.058Pa to a maximum of 1.25+/-0.003 at 0.325Pa. The fractal dimension D(2), which relates the longest axis with the projected area of the particle (A proportional to l(D(2)), increased from 1.35+/-0.014 at a shear stress of 0.058Pa to a maximum of 1.81+/-0.005 at 0.323Pa. The observed increases in D(1) and D(2) indicate that particles became more elongated with increasing shear stress. Values of the fractal dimension D(k), resulting from the Korcak's empirical law for particle population, decreased from 3.68+/-0.002 at a shear stress of 0.058Pa to 1.33+/-0.001 at 0.323Pa and indicate that the particle size distribution changed from a population of similar sized particles at low shear to larger flocculated particles at higher levels of shear. The results show that small particle clusters (micro-flocs) are the formational units of larger flocs in the water column and the stability of larger flocs is a function of the shear stress at steady state.

Environmental Monitoring↗
PubMed2003

Wear and deformation of ceramic-on-polyethylene total hip replacements with joint laxity and swing phase microseparation.

Wear of polyethylene and the resulting wear debris-induced osteolysis remains a major cause of long-term failure in artificial hip joints. There is interest in understanding engineering and clinical conditions that influence wear rates. Fluoroscopic studies have shown separation of the head and the cup during the swing phase of walking due to joint laxity. In ceramic-on-ceramic hips, joint laxity and microseparation, which leads to contact of the head on the superior rim of the cup, has led to localized damage and increased wear in vivo and in vitro. The aim of this study was to investigate the influence of joint laxity and microseparation on the wear of ceramic on polyethylene artificial hip joints in an in vitro simulator. Microseparation during the swing phase of the walking cycle produced contact of the ceramic head on the rim of the polyethylene acetabular cup that deformed the softer polyethylene cup. No damage to the alumina ceramic femoral head was found. Under standard simulator conditions the volume change of the moderately crosslinked polyethylene cups was 25.6 +/- 5.3 mm3/million cycles and this reduced to 5.6 +/- 4.2 mm3/million cycles under microseparation conditions. Testing under microseparation conditions caused the rim of the polyethylene cup to deform locally, possibly due to creep, and the volume change of the polyethylene cup when the head relocated was substantially reduced, possibly due to improved lubrication. Joint laxity may be caused by poor soft tissue tension or migration and subsidence of components. In ceramic-on-polyethylene acetabular cups wear was decreased with a small degree of joint laxity, while in contrast in hard-on-hard alumina bearings, microseparation accelerated wear. These findings may have significant implications for the choice of fixation systems to be used for different types of bearing couples.

Ceramics↗
PubMed2002

A polymerase chain reaction-based test for Verticillium fungicola causing dry bubble disease on the cultivated mushroom, Agaricus bisporus.

A polymerase chain reaction (PCR)-based test is described for the specific detection of Verticillium fungicola var. aleophilum (Vfa), the fungal pathogen causing dry bubble disease on the cultivated button mushroom, Agaricus bisporus. PCR primers were tailored to target a 162-bp arbitrary sequence in the Vfa genome. In PCR amplifications using the primer pair, all of 20 isolates of Vfa that had been collected during a 29-year period at commercial mushroom operations located primarily in North America were found to generate the diagnostic 162-bp DNA product. Conversely, the primers failed to produce the specific amplicon with DNA from isolates representing 5 other species of Verticillium, the pathogenic subspecies V. fungicola var. fungicola from Europe, and 12 other fungal species commonly inhabiting mushroom compost. A protocol was designed enabling a confirmed diagnosis of dry bubble disease in less than 3 h. The PCR-based test should find application for the rapid diagnosis and detection of the fungal pathogen in disease management programs and, potentially, in screening for on-the-farm sources of infection.

Agaricales↗
PubMed2002

Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease.

BACKGROUND: Inhaled corticosteroids form the main therapy for asthma, but there is increasing concern about the potential systematic effects of long-term inhaled corticosteroids including their effect on bone metabolism and bone loss. OBJECTIVES: To determine the effect of inhaled corticosteroids use on biochemical markers of bone turnover, bone mineral density and the development of fractures. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register, electronic reference databases, UK National Research Register, bibliographies of included studies, and contacted pharmaceutical companies. SELECTION CRITERIA: Randomised trials of the effect of inhaled steroid versus placebo on markers of bone function and metabolism, in adults with asthma or mild COPD. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extracted from the papers included (2 reviewers per paper) and from additional data supplied by the authors. MAIN RESULTS: Of 438 references found, seven met the inclusion criteria. Three studies were in healthy subjects asthma or COPD. The patients were generally less than 60 years old and the male:female ratio was 2:1. There was no evidence of increased risk of loss of bone mineral density (BMD) or fractures. There was no significant change in osteocalcin at conventional doses of inhaled corticosteroids (Standardised Mean Difference [SMD] -0.34 (95% Confidence Interval [CI] -0.72, 0.04), although a statistically significant change was seen in those studies using experimental doses of inhaled steroid in excess of the doses recommended by the British Thoracic Society SMD 0.97 (95% CI -1.61, -0.34). A statistically significant change in parathyroid hormone seen in one small short trial (n=10, 6 weeks) may have been due to the trial design and outcome measurements used. REVIEWER'S CONCLUSIONS: In patients with asthma or mild COPD, there is no evidence of an effect of inhaled corticosteroid at conventional doses given for two or three years on BMD or vertebral fracture. Higher doses were associated with biochemical markers of increased bone turnover, but data on BMD and fractures at these doses are not available. There is a need for further, even longer term prospective studies of conventional and high doses of inhaled corticosteroids.

Administration, Inhalation↗
PubMed2002

The effect of irrigation on tile sediment transport in a headwater stream.

A field-scale no-till corn plot (120 m x 90 m) located on a tile drained silt loam soil near Kintore, Ontario was irrigated with 2.5 cm of water over a 3 h period to examine the effects of irrigation on tile sediment transport in a headwater stream. Flow characteristics and the composition, concentration and size distribution of suspended solids were measured at the tile outlet, an upstream reference site and three sites located downstream of the tile drain. Results show that tile sediments at the study site are fine-grained (D50 approximately 5.0 microm) and consist primarily of quartz, anorthite/albite, dolomite and calcite. Sediment concentrations in tile effluent increased from 8 to 57 mg L(-1) after 1.5 h of irrigation and reached a maximum of 72 mg L(-1). The sediment yield from the tile drain for the irrigation event was 4.6 kg ha(-1). An unsteady, mobile boundary flow model (MOBED) was used to predict flow characteristics in the stream. According to the MOBED model, bed shear stress in the stream was approximately 6 N m(-2). This value is significantly greater than the critical shear stress for complete suspension of 1 N m(-2) for tile sediments as determined from laboratory experiments using a rotating circular flume. Grain size distributions of suspended solids in the stream were close to the dispersed size distribution because of the high shear stress in the receiving stream.

Agriculture↗
PubMed2001

Elevated function of blood clotting factor VIIa mutants that have enhanced affinity for membranes. Behavior in a diffusion-limited reaction.

Blood clotting factor VIIa is involved in the first step of the blood coagulation cascade, as a membrane-associated enzyme in complex with tissue factor (TF). Factor VIIa is also an important therapeutic agent for hemophilia where its function may include TF-independent as well as TF-dependent mechanisms. This study compared the activity of wild type factor VIIa (WT-VIIa) with that of a mutant with elevated affinity for membrane (P10Q/Q32E, QE-VIIa). Phospholipid and cell-based assays showed the mutant to have up to 40-fold higher function than WT-VIIa in both TF-dependent and TF-independent reactions. Tissue factor-dependent reactions displayed the maximum enhancement when binding had reached equilibrium in competition with another TF-binding protein. In liposome-based assays, the association rate of WT-VIIa with TF occurred at a physical maximum and could not be improved by site-directed mutagenesis. A practical consequence was identical function of WT-VIIa and QE-VIIa in assays that depended entirely on assembly kinetics. Thus, factor VIIa mutants provided unique reagents for probing the mechanism of factor VIIa action. They may also offer superior agents for therapy.

Animals↗
PubMed2001

Prenatal RHD gene determination and dosage analysis by PCR: clinical evaluation.

BACKGROUND: Use of the polymerase chain reaction (PCR) for detection of the RHD gene can measure the RHD gene status for unborn babies at risk for hemolytic disease of the newborn (HDN). The occurrence of D gene variants has led to errors in prenatal typing. Previous reports have highlighted the danger of assigning a positive fetus as negative, resulting in intrauterine fetal deaths. OBJECTIVE: To evaluate the effectiveness of a testing strategy whereby PCR was not only performed to determine the presence/absence of the RHD gene, but also used to assess the D gene copy number (zero, one or two RHD genes) in family studies for at risk pregnancies. METHODS: Samples comprising maternal (57) and paternal (42) peripheral blood samples, amniotic fluid (64), and matching cord blood (64) were collected. Rhesus (Rh) serotyping was performed on all blood samples. For RHD genotyping, DNA was extracted from all samples except for 28 cord samples, where only serotyping was performed (total 199 DNA genotyping). RHD gene PCR amplified exon 4 and exon 7 regions of the RHD gene. The dosage of RHD gene was determined by comparing the intensity of the RHD gene to that of the RHCE gene. RESULTS: A total of 197/199 samples showed concordance between exon 4 and exon 7 PCR results. Two discrepant results occurred in one family: the father carried one normal D gene and one D gene variant where PCR was tested to be positive using exon 4 but negative using exon 7. One of a pair of dizygotic twins inherited this abnormal D gene and was mildly affected by HDN. This was correctly identified antenatally and the pregnancy successfully managed. The concordance rate between serotypes and genotypes for 135 blood samples was 100%. Amongst the family groups, 8/14 heterozygous fathers transmitted the D gene and 26/26 homozygous fathers transmitted the D gene to the babies. The concordance rate between RHD genotypes from amniotic fluid and Rh D serotypes from cord blood was also 100%. CONCLUSION: The present study demonstrates the effectiveness of using PCR in a clinical setting. It verifies the importance of testing more than one region of the gene, and also the need for a testing strategy where both maternal and paternal testing for RHD gene dosages are performed.

Amniotic Fluid↗
PubMed2001

A genomic sequence analysis of the mouse and human microtubule-associated protein tau.

Microtubule associated protein tau (MAPT) encodes the microtubule associated protein tau, the primary component of neurofibrillary tangles found in Alzheimer's disease and other neurodegenerative disorders. Mutations in the coding and intronic sequences of MAPT cause autosomal dominant frontotemporal dementia (FTDP-17). MAPT is also a candidate gene for progressive supranuclear palsy and hereditary dysphagic dementia. A human PAC (201 kb) and a mouse BAC (161 kb) containing the entire MAPT and Mtapt genes, respectively, were identified and sequenced. Comparative DNA sequence analysis revealed over 100 conserved non-repeat potential cis-acting regulatory sequences in or close to MAPT. Those islands with greater than 67% nucleotide identity range in size from 20 to greater than 1700 nucleotides. Over 90 single nucleotide polymorphisms were identified in MAPT that are candidate susceptibility alleles for neurodegenerative disease. The 5' and 3' flanking genes for MAPT are the corticotrophin-releasing factor receptor (CRFR) gene and KIAA1267, a gene of unknown function expressed in brain.

Amino Acid Sequence↗
PubMed2001

Ultramicrostructure and microthermomechanics of biological IR detectors: materials properties from a biomimetic perspective.

Microstructural organization of the biological infrared (IR) receptors was studied to elucidate their materials properties useful for prospective biomimetic design of artificial IR sensors from organic/polymeric materials. The IR receptors in Melanophila acuminata beetles were studied with ultrahigh-resolution scanning probe microscopy (SPM) in a range of temperatures. By application of micromechanical mapping and thermal stage, we made attempts to reveal the micromechanical and thermomechanical properties of the cuticular apparatus of the IR sensillum. The main component of the cuticular apparatus is an internal endocuticular sphere with a diameter of about 15-20 microm. Highly ordered multilayered organization of the lamellated peripheral mantle of the sphere was confirmed and characterized. We observed that the interlayer spacing of this microstructure varied along the circumference and decreased to 300 nm in the vertex of the sphere. We demonstrated that the microlayered structure is composed of nanolayers with very different micromechanical properties and thermal behaviors. Thermal expansion of the outer mantle was observed, and the local thermal expansion coefficient under given preparation conditions was estimated to be below 1.5 x 10(-4) grad(-1).

Animals↗
PubMed2001

Biological thermal detection in infrared imaging snakes. 1. Ultramicrostructure of pit receptor organs.

The receptor organs of snakes with "thermal vision" were studied with ultra-high-resolution scanning probe microscopy (SPM) at close to in vivo conditions to elucidate their surface morphology and materials properties critical for prospective biomimetic design of "soft matter"-based infrared (IR) sensors. The surfaces of living tissues were scanned under wet ambient conditions in physiological solution, and the resulting parameters were compared with SPM data obtained for chemically treated (formaldehyde-fixed) tissue in ambient air and TEM studies in high vacuum. We found that the microstructural parameters for the living tissue are similar to ones observed for the formaldehyde-fixed snake tissues. However, previous data obtained from TEM analysis in high vacuum underestimated actual dimensions of surface microstructures. The average spacing of the nanopit array observed within receptor surface areas, which was suggested to play a critical role in selective IR adsorption, was determined to be 520 nm. This value is close to the grating spacing required for efficient reflection of electromagnetic radiation characteristic for sunlight without affecting IR adsorbance.

Animals↗
PubMed2001

Proteins containing the UBA domain are able to bind to multi-ubiquitin chains.

The UBA domain is a motif found in a variety of proteins, some of which are associated with the ubiquitin-proteasome system. We describe the isolation of a fission-yeast gene, mud1+, which encodes a UBA domain containing protein that is able to bind multi-ubiquitin chains. We show that the UBA domain is responsible for this activity. Two other proteins containing this motif, the fission-yeast homologues of Rad23 and Dsk2, are also shown to bind multi-ubiquitin chains via their UBA domains. These two proteins are implicated, along with the fission-yeast Pus1(S5a/Rpn10) subunit of the 26 S proteasome, in the recognition and turnover of substrates by this proteolytic complex.

Amino Acid Motifs↗
PubMed2001

Modeling tongue surface contours from Cine-MRI images.

This study demonstrated that a simple mechanical model of global tongue movement in parallel sagittal planes could be used to quantify tongue motion during speech. The goal was to represent simply the differences in 2D tongue surface shapes and positions during speech movements and in subphonemic speech events such as coarticulation and left-to-right asymmetries. The study used tagged Magnetic Resonance Images to capture motion of the tongue during speech. Measurements were made in three sagittal planes (left, midline, right) during movement from consonants (/k/, /s/) to vowels (/i/, /a/, /u/). MR image-sequences were collected during the C-to-V movement. The image-sequence had seven time-phases (frames), each 56 ms in duration. A global model was used to represent the surface motion. The motions were decomposed into translation, rotation, homogeneous stretch, and in-plane shear. The largest C-to-V shape deformation was from /k/ to /a/. It was composed primarily of vertical compression, horizontal expansion, and downward translation. Coarticulatory effects included a trade-off in which tongue shape accommodation was used to reduce the distance traveled between the C and V. Left-to-right motion asymmetries may have increased rate of motion by reducing the amount of mass to be moved.

Adult↗
PubMed2001

Prospective memory in dynamic environments: effects of load, delay, and phonological rehearsal.

A new paradigm was developed to examine prospective memory performance in a visual-spatial task that resembles some aspects of the work of air traffic controllers. Two experiments examined the role of workload (number of aeroplanes that participants directed), delay (between receipt of prospective instructions and execution), and phonological rehearsal. High workload increased prospective memory errors but increasing delay from 1-3 or 5 minutes had no effect. Shadowing aurally presented text reduced prospective memory performance, presumably because it prevented verbal rehearsal of the prospective instructions. However, performance on the foreground task of directing aeroplanes to routine destinations was affected only by workload and not by opportunity for rehearsal. Our results suggest that ability to maintain performance on a routine foreground task while performing a secondary task--perhaps analogous to conversation--does not predict ability to retrieve a prospective intention to deviate from the routine.

Adolescent↗
PubMed2001

Modeling the motion of the internal tongue from tagged cine-MRI images.

A new technique, tagged Cine-Magnetic Resonance Imaging (tMRI), was used to develop a mechanical model that represented local, homogeneous, internal tongue deformation during speech. The goal was to infer muscle activity within the tongue from tissue deformations seen on tMRI. Measurements were made in three sagittal slices (left, middle, right) during production of the syllable /ka/. Each slice was superimposed with a grid of tag lines, and the approximately 40 tag line intersections were tracked at 7 time-phases during the syllable. A local model, similar to a finite element analysis, represented planar stretch and shear between the consonant and vowel at 110 probed locations within the tongue. Principal strains were calculated at these locations and revealed internal compression and extension patterns from which inferences could be drawn about the activities of the Verticalis, Hyoglossus, and Superior Longitudinal muscles, among others.

Adult↗
PubMed2001

Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients.

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.

Adult↗
PubMed2001

Clinical and imaging correlates of response to treatment with infliximab in patients with ankylosing spondylitis.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic disease leading to progressive spinal ankylosis and deformity. The aims of this study were to (1) determine whether infliximab is an effective treatment for AS patients who have failed conventional treatment; (2) identify any baseline clinical variables that can be associated with responsiveness to treatment; and (3) resolve whether the clinical response correlated with changes from baseline inflammatory changes on magnetic resonance imaging (MRI). METHODS: Twenty-one patients who met the modified New York criteria for AS (M:F 18:3) were enrolled in this open labeled study. The mean age was 37.9+/-7.9 years and mean disease duration was 8.69+/-6.58 years. Patients received infliximab at a dose of 5 mg/kg by intravenous infusion over 2 hours at 0, 2, 6, weeks. Nine functional variables were measured [i.e., Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI) etc.], 6 clinimetrics (chest expansion, finger to floor, etc.), and inflammatory markers in the peripheral blood at baseline and each subsequent visit. Primary response to treatment was defined as a > 20% response in 5/9 functional variables. A subset of 9 consecutive patients was selected for MRI scans before and after infusions. RESULTS: Eighteen patients were available for assessment at week 14 having received 3 infusions (wks 0, 2, 6). There was > 60% improvement in functional variables, i.e., BASDAI, BASFI, Health Assessment Questionnaire, fatigue, and spinal and total body pain. Clinimetric scores selectively improved, e.g., chest expansion (p < 0.021) by 14 weeks. ESR, CRP and haptoglobin all showed significant improvement at 6 weeks and were maintained to the 14 week assessment point. Imaging studies showed improvement in all patients studied including those with advanced disease. Three patients developed headache during the infusions. Infliximab was effective in all, but degree of response varied. Very good responders were distinguished from good responders by shorter duration of disease and better baseline clinimetric scores. CONCLUSIONS: Infliximab was an effective treatment for AS in a short term trial. Longterm control of symptoms and potential alteration in clinical course of disease will require longterm assessment.

Achilles Tendon↗
PubMed2001

Power Doppler ultrasound assessment of rheumatoid hand synovitis.

OBJECTIVE: To evaluate power Doppler ultrasound (PD) as a technique in assessing response to treatment with steroids in rheumatoid hand synovitis. METHODS: Twelve patients with rheumatoid hand synovitis were assessed before and after treatment with steroids. Variables used to assess synovitis activity in each patient included patient visual analog scale (VAS) score for pain, physician assessment score (PAS), erythrocyte sedimentation rate (ESR), and PD of the metacarpophalangeal joints. RESULTS: Nine female and 3 male patients were studied; mean age was 53.3+/-6.5 yrs and mean disease duration 6.5+/-4.5 yrs. All patients had a good clinical response to steroid treatment and there was a significant improvement in the synovitis activity assessments. Wilcoxon signed-rank test using the exact method was applied to the change in disease activity variables. For PD signal, p < 0.002; VAS, p < 0.0016; ESR, p < 0.031; PAS, p < 0.008. CONCLUSION: PD quantifies synovitis and may be a useful adjunct to disease assessment and the response to treatment in RA.

Adult↗