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Biomedical subjects

P Williams

Publications and source records attributed to P Williams.

At least 217 records · Page 12Linked to original sources
PubMed1997

High-resolution MR of the intraparotid facial nerve and parotid duct.

PURPOSE: To describe a high-resolution MR imaging technique that depicts the complex anatomy of the region of the parotid gland, focusing on the intraparotid components of the facial nerve and parotid duct. METHODS: High-resolution T1-weighted images of the parotid gland were acquired with a prototype three-dimensional Fourier transform gradient-echo sequence that permits a very short echo time (4.2 milliseconds) by using a modified phase-encoded time-reduced acquisition scheme. The sequences were obtained at 1.5 T with a head and neck coil. Postprocessed multiplanar, curved and volumetric images were obtained. The most clinically useful images were acquired at parameters of 40/4.2 (TR/TEeff) a flip of 30 degrees, a field of view of 18 to 20 cm, a matrix of 512 x 288 or 512 x 256, an axial plane, 60 images, no gaps, and a section thickness of 1.5 mm. Eighteen healthy subjects were examined. The position of the facial nerve within the parotid gland was determined by identifying the facial nerve in the stylomastoid foramen and then following it on sequential sections through the parotid gland. Curved reformations were used to confirm the visibility of the nerve. A similar technique was used for the parotid duct. RESULTS: The image contrast obtained was similar to that of standard spin-echo T1-weighted images. The parotid gland showed intermediate signal intensity while the fat spaces showed high signal intensity. The vessels had variable signal intensity depending on saturation. The cerebrospinal fluid, nerves, muscles, and ducts had lower signal intensity. In all 18 subjects, the facial nerve from the brain stem to the parotid gland, and the parotid duct from the mouth to the hilus of the gland were seen bilaterally. The proximal intraparotid facial nerve to the level of the retromandibular vein was seen in 72% of the subjects and the main intraparotid ducts were seen in 66% of the subjects. CONCLUSION: High-resolution MR imaging offers simultaneous display of most of the important structures in the region of the parotid gland, including the intraparotid duct and facial nerve.

Adult↗
PubMed1996

Identification of a novel bone/calcium metabolism-regulating factor in porcine pancreas.

We purified from porcine pancreas a hypocalcemic peptide clearly distinguishable from other pancreatic osteotropic factors such as amylin, calcitonin, and glucagon. Porcine pancreas was processed by acetone extraction, anion exchange chromatography, isoelectric focusing, and reverse-phase high performance liquid chromatography. Fractions were assayed for their inhibitory effects on bone resorption in vitro. Amino acid sequence of a homogeneous 28-kDa protein revealed 92% homology to a human elastase IIIB in the N terminus. Recombinant human elastase IIIB (rhEIIIB) inhibited bone resorption in organ culture stimulated by 1,25-dihydroxyvitamin D3 at concentrations as low as 75 ng/ml. Antibodies to rhEIIIB recognized purified pancreatic factor in Western blots and blocked its inhibitory effect on bone resorption. This antiresorptive activity was abolished by phenylmethylsulfonyl fluoride, suggesting the importance of elastase proteolytic activity for inhibition of bone resorption. In vivo, rhEIIIB and purified pancreatic factor significantly decreased recombinant human interleukin-1alpha-induced hypercalcemia. In conclusion, a novel naturally occurring inhibitor of bone resorption and calcium-lowering peptide has been identified in porcine pancreas. Because this pancreatic peptide has systemic effects on bone resorption and blood ionized calcium at low concentrations, it may represent a physiological regulator of normal bone remodeling and calcium homeostasis.

Amino Acid Sequence↗
PubMed1996

Structural characterization of red wine rhamnogalacturonan II.

The pectic polysaccharide rhamnogalacturonan II (RG-II), which accounts for approximately 20% of the ethanol-precipitable polysaccharides in red wine, has been isolated from wine polysaccharides by anion-exchange chromatography. Four fractions enriched with RG-II were obtained and the RG-II then purified to homogeneity by Concanavalin A affinity and size-exclusion chromatographies. The glycosyl-residue compositions of the four RG-IIs are similar; all the RG-IIs contain the monosaccharides (apiose, 2-O-methyl-L-fucose, 2-O-methyl-D-xylose, Kdo, Dha, and aceric acid) that are diagnostic of RG-II. The glycosyl-linkages of the neutral and acidic sugars, including aceric acid, were determined simultaneously by GC-EIMS analysis of the methylated alditol acetates generated from per-O-methylated and carboxyl-reduced RG-II. Two of the RG-IIs contain boron, most likely as a borate di-ester that cross-links two molecules of RG-II together to form a dimer. The dimer contains 3'- and 2,3,3'-linked apiosyl residues whereas the monomer contains only 3'-linked apiosyl residues which suggests that the borate di-ester is located on at least one of the apiosyl residues of RG-II. Although the wine RG-IIs all have similar structures they are not identical since they differ in the length and degree of methyl-esterification of the RG-II backbone and in the presence or absence of borate di-esters. Nevertheless, these studies show that the major structural features of wine and primary cell wall RG-II are conserved.

Borates↗
PubMed1996

Purification and characterization of LasR as a DNA-binding protein.

In Pseudomonas aeruginosa, the activator protein LasR and a cognate autoinducer (AI) are required for expression of the elastase gene (lasB). In the present study, we investigated the binding properties of the P. aeruginosa lasR gene product. The LasR protein was overexpressed and purified as a glutathione S-transferase (GST) fusion protein. Using gel retardation and UV cross-linking analysis, we demonstrated that the GST-LasR could bind to a separate site in the lasB upstream operator regions 1 and 3 in the presence of the autoinducer. Regions 1 and 3 are located at 105 and 42 base pairs upstream, respectively, from the lasB transcriptional start site. Our present results clearly demonstrate that LasR is a specific DNA-binding protein that regulates the transcription of the lasB gene in the presence of an autoinducer.

4-Butyrolactone↗
PubMed1996

Production of cadmium sulphide microcrystallites in batch cultivation by Schizosaccharomyces pombe.

Cadmium sulphate was added to separate batch cultures of Schizosaccharomyces pombe during different growth phases to determine the effect on cadmium sulphide microcrystallite production. Exit gas analysis was used to determine the impact on metabolism. Addition during the early-exponential growth phase resulted in an immediate intracellular uptake of cadmium, followed by rapid efflux from the cells, permanent reduction in cell metabolism and a lower intracellular inorganic sulphide content. This response was not suitable for cadmium sulphide microcrystallite production. Stationary phase cultures did not induce cadmium sulphide microcrystallite production. However, the addition of cadmium sulphate to a culture during the mid-exponential growth phase increased the intracellular cadmium and inorganic sulphide concentrations for approximately 8 h before reaching a saturation level for the cell. This resulted in a significant level of cadmium sulphide microcrystallite production.

Biological Transport, Active↗
PubMed1996

Cell transfer by filtration: evaluation of protocols for transformational competence.

Collection and washing of cells by centrifugation is a time consuming and inconvenient component of many microbiological protocols, especially when sterility must be maintained. Filtration onto disposable membrane filters efficiently replaced the centrifugation steps in standard transformational competence protocols for Escherichia coli, Haemophilus influenzae, and Saccharomyces cerevisiae. With all three protocols filtered cells were competent sooner and showed transformation efficiencies comparable to or higher than those of cells prepared by centrifugation. The procedure can be easily adapted to collect cells for many other purposes, and should be especially useful in metabolic studies and in preparing cells for electroporation, as it facilitates both thorough washing and rapid but gentle resuspension of cells without compromising sterility.

Electroporation↗
PubMed1996

Affinity methods for purification of DNA sequencing reaction products for mass spectrometric analysis.

Time-of-flight mass spectrometry has the potential to replace gel electrophoresis for rapid and accurate analysis of DNA sequencing mixtures. However, impurities in the Sanger sequencing reaction solutions can complicate and degrade the mass spectrometric performance. Therefore, a fast purification procedure is necessary for mass spectrometric analysis. Two affinity methods were tested for the capture of the target fragments: a probe strand, complementary to the primer used to initiate synthesis of the Sanger fragments, is immobilized to a solid support either before or after hybridization so that the impurities are readily separated by filtering and washing the support material. The approaches were tested using mock sequencing mixtures assembled from synthetic DNA strands, to which representative impurities could be added. The results showed that the latter method has better overall yield. The recovered fragments were analyzed by matrix-assisted laser desorption/ionization.

Bacterial Proteins↗
PubMed1996

Intelligence and the frontal lobe: the organization of goal-directed behavior.

Basic to the study of individual differences is the concept of 'general intelligence' or Spearman's g. In this article we suggest that g is largely a reflection of the control functions of the frontal lobe. A series of experiments investigates a phenomenon we call goal neglect: disregard of a task requirement event though it has been understood and remembered. Subjectively it is as though the neglected requirement "slips the subject's mind." Previously described in frontal patients, we show that goal neglect can also be seen in some members of the normal population. In line with conventional distinctions between controlled and automatic processing, eliciting conditions for goal neglect include novelty, weak error feedback, and multiple concurrent task requirements. Under these conditions neglect is linked closely to g and extremely common after frontal lesions. Following many other models, we suggest that behavior in any task is structured by a set of action constraints or requirements, derived in part from verbal instructions and specified at multiple levels of abstraction. A frontal process of constraint or requirement activation is fundamental to Spearman's g.

Adult↗
PubMed1996

The effects of a community exercise program on fracture risk factors in older women.

One hundred and seventy-nine women aged 60-85 years (mean age 71.6 years, SD 5.3 years) were randomly recruited from the community to participate in a 12-month randomized controlled trial to determine whether a program of twice-weekly structured exercise has beneficial effects on three factors associated with osteoporotic fractures: quadriceps strength, postural sway and bone density. At initial testing, there were no significant differences in the strength, sway and bone density measures (assessed at the hip and lumbar spine) between the exerciser and control groups. The exercise classes included strengthening, coordination and balance exercises, and approximately 35 min of each class comprised weight-bearing exercise. The mean number of classes attended for the 68 exercisers who completed the program was 59.8 of the 82 classes (72.9%). At the completion of the trial, the intervention group showed significant improvements in quadriceps strength and sway but not bone mineral density when compared with the control group. Indices of fracture risk, indicated by (i) the sum of standard score results and (ii) the sum of quartile grades of the femoral neck bone density, sway and strength measures, decreased significantly in the exercisers at the end of the trial compared with the controls. In conclusion, the program of general aerobic exercise may have reduced overall fracture risk, even though it did not significantly increase bone density. Further long-term studies are required that include acceptable weight-loaded exercises to determine optimal programs for reducing fracture risk factors by improving bone density as well as strength and balance.

Activities of Daily Living↗
PubMed1996

Allogeneic bone marrow transplantation for poor-prognosis lymphoma: response, toxicity and survival depend on disease histology.

PURPOSE: To evaluate outcomes and identify prognostic factors in allogeneic bone marrow transplantation in patients with end-stage lymphoma. PATIENTS AND METHODS: Data were retrospectively analyzed of 64 patients (42 men and 22 women) 18 to 48 years of age with recurrent or refractory lymphoma who underwent allogeneic bone marrow transplantation from matched sibling donors (or in 1 case from a one antigen-mismatched relative) between May 1981 and July 1994. RESULTS: Twelve patients survived free of disease. They were 8 of 15 with low-grade lymphoma (disease-free survival at 2 years 59% +/- 13%); 3 of 25 with lymphoblastic lymphoma (disease-free survival 17% +/- 8%); and 1 of 10 with diffuse small non-cleaved cell lymphoma (disease-free (10% +/- 9%). Survival and disease-free survival of patients with low-grade lymphoma were significantly superior compared to any other subgroup of patients (P <0.01). Only 2 patients with low-grade lymphoma had disease progression (9% +/- 9% actuarial risk at 2 years) as opposed to 5 of 15 with intermediate-grade lymphoma (39% +/- 14%), 9 of 25 with lymphoblastic lymphoma (28% +/- 9%), and 8 of 10 (80% +/- 13%) with diffuse small non-cleaved lymphoma. The actuarial risk for disease progression was significantly lower for patients with low-grade lymphoma than for any other histologic subgroup (P <0.02). It was significantly higher for those with diffuse small non-cleaved cell lymphoma than for other histologic subgroups (P < or = 0.003). CONCLUSIONS: Allogeneic bone marrow transplantation is an effective procedure in patients with refractory low-grade lymphoma. It results in long-term remissions and should be considered in younger patients with recurrent disease who have a matched sibling donor. The late recurrence in 1 patient indicates the necessity of continued follow-up. A small fraction of patients with end-stage intermediate- and high-grade lymphoma can obtain prolonged disease-free survival, but recurrence and regimen-related toxicity remain major problems. The results could be improved by the development of conditioning regimens with less toxicity and by the use of bone marrow transplantation earlier in the course of the disease.

Adolescent↗
PubMed1996

Exercise effect on dynamic stability in older women: a randomized controlled trial.

OBJECTIVE: To determine whether a 12-month program of regular exercise can improve dynamic postural stability in older women. DESIGN: Randomized controlled trial of 12 months' duration. SETTING: Conducted as part of the Randwick Falls and Fractures Study, in Sydney, Australia. PARTICIPANTS: One hundred and twelve community-dwelling women aged 60 to 85 years (mean age 71.2, SD = 5.4). OUTCOME MEASURES: Quantitative measures of dynamic postural stability: maximal balance range and coordinated stability. MAIN RESULTS: Exercise and control subjects were tested before, midway through, and at the end of the trial. The stability measures had good test-retest reliability, and test performances were significantly associated with measures of lower limb muscle strength, reaction time, neuromuscular control, and body sway. At initial testing, exercisers and controls performed similarly in the two stability measures. The mean number of classes attended for the 48 exercise subjects who completed the program was 58.4 (range 26-77). At the end of the trial, the exercise subjects showed significantly improved performance in both the maximal balance range and coordinated stability tests, with no improvement evident in the controls. Improvements in coordinated stability were associated with corresponding improvements in ankle dorsiflexion, hip extension, and hip flexion strength. CONCLUSION: These findings show that exercise can significantly improve dynamic postural stability in older persons and elucidate some possible mechanisms by which such improvements may be mediated.

Accidental Falls↗
PubMed1996

A hierarchical quorum-sensing cascade in Pseudomonas aeruginosa links the transcriptional activators LasR and RhIR (VsmR) to expression of the stationary-phase sigma factor RpoS.

In Pseudomonas aeruginosa, the production of many virulence factors and secondary metabolites is regulated in concert with cell density through quorum sensing. Two quorum-sensing regulons have been identified in which the LuxR homologues LasR and RhlR are activated by N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and N-butanoyl-L-homoserine lactone (BHL) respectively. The lasR and rhlR genes are linked to the luxl homologues lasl and rhll, which are responsible for synthesis of OdDHL and BHL, respectively. As lasRl and rhlRl are both involved in regulating synthesis of exoenzymes such as elastase, we sought to determine the nature of their interrelationship. By using lacZ transcriptional fusions in both homologous (P. aeruginosa) and heterologous (Escherichia coli) genetic backgrounds we provide evidence that (i) lasR is expressed constitutively throughout the growth cycle, (ii) rhlR expression is regulated by LasR/OdDHL, and (iii) that RhlR/BHL regulates rhll. We also show that expression of the stationary-phase sigma factor gene rpoS is abolished in a P. aeruginosa lasR mutant and in the pleiotropic BHL-negative mutant PANO67. Furthermore, our data reveal that kin E. coli, an rpoS-lacZ fusion is regulated directly by RhlR/BHL. Taken together, these results indicate that P. aeruginosa employs a multilayered hierarchical quorum-sensing cascade involving RhlR/BHL and LasR/OdDHL, interlinked via RpoS, to integrate the regulation of virulence determinants and secondary metabolites with adaptation and survival in the stationary phase.

Bacterial Proteins↗
PubMed1996

The effect of exercise on gait patterns in older women: a randomized controlled trial.

BACKGROUND: This study was undertaken to determine (a) whether a program of regular exercise can improve gait patterns in older women, and (b) whether any such improvement in gait is mediated by increased lower limb muscle strength. METHOD: A 22-week randomized controlled trial of exercise was conducted as part of the Randwick Falls and Fractures Study in Sydney, Australia. Subjects were 160 women aged 60-83 years (Mean age 71.1, SD = 5.2) who were randomly recruited from the community. Exercise and control subjects were tested prior to and at the end of the trial. At initial testing, exercisers and controls performed similarly in the strength and gait parameters. They were well matched in terms of age and a number of health and life-style characteristics. RESULTS: At the end of the trial, the exercise subjects showed improved strength in five lower limb muscle groups, increased walking speed, cadence, stride length, and shorter stride times as indicated by both reduced swing and stance duration. There were no significant improvements in any of the strength or gait parameters in the controls. Within the exercise group, increased cadence was associated with improved ankle dorsiflexion strength, and increased stride length was associated with improved hip extension strength. Exercise subjects with initial slow walking speed showed greater changes in velocity, stride length, cadence, and stance duration than those with initial fast walking speed. CONCLUSION: These findings show that exercise can increase gait velocity and related parameters in older persons, and that part of this increase may be mediated by improved lower limb muscle strength.

Aged↗
PubMed1996

Conservation and antigenic cross-reactivity of the transferrin-binding proteins of Haemophilus influenzae, Actinobacillus pleuropneumoniae and Neisseria meningitidis.

Haemophilus influenzae acquires iron from the iron-transporting glycoprotein transferrin via a receptor-mediated process. This involves two outer-membrane transferrin-binding proteins (Tbps) termed Tbp1 and Tbp2 which show considerable preference for the human form of transferrin. Since the Tbps are attracting considerable attention as potential vaccine components, we used transferrin affinity chromatography to examine their conservation amongst 28 H. influenzae type b strains belonging to different outer-membrane-protein subtypes as well as six non-typable strains. Whole cells of all type b and non-typable strains examined bound human transferrin; whilst most strains possessed a Tbp1 of approximately 105 kDa, the molecular mass of Tbp2 varied from 79 to 94 kDa. Antisera raised against affinity-purified native H. influenzae Tbp1/Tbp2 receptor complex cross-reacted on Western blots with the respective Tbps of all the Haemophilus strains examined. When used to probe Neisseria meningitidis Tbps, sera from each of four mice immunized with the Haemophilus Tbp1/2 complex recognized the 68 kDa Tbp2 of N. meningitidis strain B16B6 but not the 78 kDa Tbp2 of N. meningitidis strain 70942. Serum from one mouse also reacted weakly with Tbp1 of strain B16B6. Apart from a weak reaction with the Tbp2 of a serotype 5 strain, this mouse antiserum failed to recognize the Tbps of the porcine pathogen A. pleuropneumoniae. However, a monospecific polyclonal antiserum raised against the denatured Tbp2 of Neisseria meningitidis B16B6 recognized the Tbps of all Haemophilus and Actinobacillus strains examined. Since H. influenzae forms part of the natural flora of the upper respiratory tract, human sera were screened for the presence of antibodies to the Tbps. Sera from healthy adults contained antibodies which recognized both Tbp1 and Tbp2 from H. influenzae but not N. meningitidis. Convalescent sera from meningococcal meningitis patients contained antibodies which, on Western blots, recognized the Tbps2s of both pathogens. These data demonstrate the existence of shared epitopes on the Tbps of H. influenzae, N. meningitidis and A. pleuropneumoniae despite their transferrin species specificity.

Actinobacillus pleuropneumoniae↗
PubMed1996

Involvement of N-acyl-L-hormoserine lactone autoinducers in controlling the multicellular behaviour of Serratia liquefaciens.

Several bacterial species possess the ability to differentiate into highly motile swarmer cells capable of rapid surface colonization. In Serratia liquefaciens, we demonstrate that initiation of swarmer-cell differentiation involves diffusible signal molecules that are released into the growth medium. Using high-performance liquid chromatography (HPLC), high resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, we identified N-butanoyl-L-homoserine lactone (BHL) and N-hex anoyl-L-homoserine lactone (HHL) in cell-free Serratia culture supernatants. BHL and HHL are present in a ratio of approximately 10:1 and their structures were unequivocally confirmed by chemical synthesis. The swrl (swarmer initiation) gene, the predicted translation product of which exhibits substantial homology to the LuxI family of putative N-acyl homoserine lactone (AHL) synthases is responsible for directing synthesis of both BHL and HHL. In an swrl mutant, swarming motility is abolished but can be restored by the addition of an exogenous AHL. These results add swarming motility to the rapidly expanding list of phenotypes known to be controlled through quorum sensing.

4-Butyrolactone↗