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Biomedical subjects

K M Williams

Publications and source records attributed to K M Williams.

At least 73 records · Page 4Linked to original sources
PubMed1994

The stereoselective disposition of the enantiomers of ibuprofen in blood, blister and synovial fluid.

1. A sensitive, stereospecific assay using gas chromatography-mass spectrometry (GC/MS) was established to measure the concentrations of the enantiomers of ibuprofen in small volumes (50 microliters) of blister fluid. 2. The concentrations of the enantiomers in blister fluid, assessed in eight patients, were similar to those in synovial fluid, both fluids behaving as peripheral compartments with respect to plasma. 3. The mean rate constants of transfer of R-ibuprofen into (0.14 +/- 0.06 h-1) and out of (0.20 +/- 0.04 h-1) blister fluid were not significantly different from those for synovial fluid (0.19 +/- 0.12 h-1, 0.34 +/- 0.11 h-1, respectively). Similarly, the mean rate constants of transfer of S-ibuprofen into (0.22 +/- 0.07 h-1) and out of (0.27 +/- 0.08 h-1) blister fluid were not significantly different from those for synovial fluid (0.29 +/- 0.10, 0.36 +/- 0.11 h-1). However, the correlations were poor between the transfer constants for each of the enantiomers between plasma, and both blister and synovial fluid (P > 0.2). 4. The complex rate constant of transfer of S-ibuprofen into blister fluid (0.22 +/- 0.07 h-1) was greater than that of R-ibuprofen (0.14 +/- 0.07 h-1), which may be explained by the lesser protein binding of the S-enantiomer.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1994

Electrophoretic analysis of cat parotid saliva in response to parasympathetic stimulation or infusion of bethanechol.

The protein constituents of cat parotid saliva evoked by parasympathetic stimulation or the infusion of bethanechol have been compared by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The SDS-PAGE patterns were highly reproducible for an individual cat and revealed up to 30 polypeptide bands in microlitre volumes of unconcentrated saliva. Only minor and predominantly quantitative differences were detected in the salivary protein composition of different cats. SDS-PAGE demonstrates quantitative rather than qualitative changes in the protein composition of saliva evoked in response to different stimuli. The latter included preliminary observations on the effect of vasoactive intestinal peptide (VIP) on the bethanechol-evoked response.

Animals↗
PubMed1994

Serum antibodies from patients with ankylosing spondylitis and Reiter's syndrome are reactive with HLA-B27 cells transfected with the Mycobacterium tuberculosis hsp60 gene.

HLA-B27-related arthritis is probably mediated by an immune response against HLA-B27 complexed with peptides derived from proteins of arthritis-causing bacteria. Immunogenic proteins with a high degree of homology among bacteria, such as in the hsp60 family, are likely candidates. To create such complexes experimentally, we transfected an HLA-B27 cell line with the Mycobacterium tuberculosis hsp60 gene. Because of previous observations that HLA-B27-peptide complexes can be distinguished by antibodies, we tested the transfected cell line with a panel of sera from 24 HLA-B27+ arthritis patients. Significant antibodies were detected in at least eight of the sera. Several cell lines and peptides were used as negative controls to ensure that the antibody reactivity was specific to HLA-B27-peptide complexes. A panel of nine peptides derived from the sequence of the Mycobacterium hsp60 were synthesized and tested. At least three were identified as being responsible for the serological activities.

Amino Acid Sequence↗
PubMed1994

Analysis of snake venoms by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional electrophoresis.

The protein composition of snake venom has been analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and high resolution two-dimensional electrophoresis (2-DE) with comparison of our simplified Tris/glycine/SDS (TGS) method with a commercial Tris/Tricine/SDS (TTS) gel system. SDS-PAGE suggests differences between species and similarities between related species but 2-DE indicates that the protein composition of the venoms is highly complex. The TTS system improves resolution upon 2-DE but our simplified TGS method is optimal for silver staining which, contrary to previous reports, enhances detection 100-fold.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1993

Electrophoretic analysis of stimulated cat parotid saliva.

The proteins of parasympathetically stimulated cat parotid saliva were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and high resolution two-dimensional electrophoresis (2-DE). SDS-PAGE revealed up to 30 polypeptide bands in microliter volumes of unconcentrated saliva. The patterns were highly reproducible and characterized by prominent bands of M(r) 57,000, M(r) 30,000 and M(r) 15,000. The major protein (M(r) 30,000) appeared as a dimer (M(r) 60,000) when electrophoresed under non-reducing conditions but dissociated into its monomeric form when the SDS concentration of the denatured samples was increased from 1 to 5%. This indicates a noncovalent association. The protein patterns of saliva from different cats differed slightly but sequential samples from the same cat (collected during 90 min of stimulation) showed little change in protein pattern apart from a fall in total protein content. Following 2-DE, the major protein (M(r) 30,000) appeared as a complex array of at least eight spots in two tiers (pI 5.2-6.2; M(r) 28,000 and 32,000). The characteristics of this protein are discussed with reference to allergy to cats.

Animals↗
PubMed1993

Bradford protein assay and the transition from an insoluble to a soluble dye complex: effects of sodium dodecyl sulphate and other additives.

The addition of sodium dodecyl sulphate (SDS) (0.0015-0.006%), phenol (0.25-0.5%) or sodium hydroxide (0.025-0.1 M) to the Bradford dye reagent does not improve the solubility of the Coomassie blue-protein dye complex. Centrifugation of the assay tubes, 10 min after the addition of reagent, results in complete loss of colour yield as indicated by the absorbance (A595) of the recovered supernates. At protein-concentrations above the working range of the assay, centrifugation indicates a transition from an insoluble to a soluble protein-dye complex. This transition is characteristic of an individual protein and is influenced by assay modification. Low protein concentrations appear to provide nucleation sites for precipitation of Coomassie blue whilst higher protein concentrations increase its solvation. A soluble dye chromophore is only formed above the working range of the assay indicating that precipitation of the dye by protein contributes to the assay mechanism.

Centrifugation↗
PubMed1993

Duplex sonography in detection of renal artery stenosis: a simplified approach using new parameters.

A case report illustrating a new investigation for detecting renal artery stenosis (RAS) is reported. Colour Doppler ultrasound evaluation of the readily accessible intrarenal arteries is a fast and accurate technique. Acceleration time and acceleration are the Doppler parameters used for measuring systolic upstroke on the waveforms obtained. Prolonged acceleration time (> or = 0.07s) and diminished acceleration (< or = 3 m/s2) indicate haemodynamically significant stenosis. Intrarenal Doppler ultrasound should provide a safe noninvasive screening examination for the detection of RAS.

Adult↗
PubMed1993

Chiral NSAIDS: so what?

There are often both pharmacodynamic and pharmacokinetic differences between enantiomers. Intuitively then, the use of single enantiomers of chiral NSAIDs is preferable to administering the racemate and monitoring the "active" enantiomer in studies involving racemic drugs is preferred. However, limited clinical studies of (S)-2-arylpropionates, while demonstrating expected antiinflammatory activity, have not yet improved attempts to establish concentration-effect relationships for these drugs. This may be because actions of the "inactive" (R)-enantiomers are important or it may be a reflection of a greater variability in other factors such as the disease itself and methods to assess disease activity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Prevalence of substance use among US physicians.

OBJECTIVE: To estimate the prevalence of substance use among US physicians. DESIGN: A mailed, anonymous, self-report survey that assessed use of 13 substances and permitted comparison with results of the National Household Survey on Drug Abuse. Rates of physician substance use were weighted to provide national prevalence estimates. PARTICIPANTS: A national sample of 9600 physicians, stratified by specialty and career stage, and randomly selected from the American Medical Association master file. The response rate after three mailings was 59%. Demographic characteristics of respondents closely reflected those of the US physician population. MAIN OUTCOME MEASURES: Subjects' self-reported use of 13 substances in their lifetime, the past year, and the past month; reasons for use; self-admitted substance abuse or dependence; and whether treatment was received. For controlled prescription substances, respondents were asked to report only use "not prescribed by another physician for a legitimate medical or psychiatric condition." RESULTS: Physicians were less likely to have used cigarettes and illicit substances, such as marijuana, cocaine, and heroin, in the past year than their age and gender counterparts in the National Household Survey on Drug Abuse. They were more likely to have used alcohol and two types of prescription medications--minor opiates and benzodiazepine tranquilizers. Prescription substances were used primarily for self-treatment, whereas illicit substances and alcohol were used primarily for recreation. Current daily use of illicit or controlled substances was rare. CONCLUSIONS: Although physicians were as likely to have experimented with illicit substances in their lifetime as their age and gender peers in society, they were far less likely to be current users of illicit substances. The higher prevalence of alcohol use among respondents may be more a characteristic of their socioeconomic class than of their profession. A unique concern for physicians, however, is their high rate of self-treatment with controlled medications--a practice that could increase their risk of drug abuse or dependence. Uniform national guidelines are needed to sensitize medical students and physicians to the dangers of self-treatment with controlled prescription substances.

Adult↗
PubMed1992

The effect of the enantiomers of ibuprofen and flurbiprofen on the beta-oxidation of palmitate in the rat.

The effects of the enantiomers of ibuprofen (0.25 and 0.50 mmol/kg b.w.) and flurbiprofen (0.01, 0.03, and 0.06 mmol/kg b.w.) on the beta-oxidation of palmitate were investigated in the rat. The mean cumulative exhalation of 14CO2 after ip administration of [U-14C]palmitic acid was significantly reduced over 6 h by ibuprofen at the higher dose but not at the lower dose for either enantiomer. There was no difference between the enantiomers, the reduction over 6 h being 31.3 and 33.0% for (R)- and (S)-ibuprofen, respectively. There was also a significant inhibition of beta-oxidation by flurbiprofen at all 3 doses. Again, there was no stereoselectivity evident in this inhibition. Flurbiprofen was much more potent than ibuprofen in eliciting this effect, the 0.01mmol/kg dose giving a similar reduction in beta-oxidation as observed for the 0.50 mmol/kg dose of ibuprofen. The data support the hypothesis that inhibition of the in vivo beta-oxidation of palmitate by ibuprofen and flurbiprofen is primarily via a nonstereoselective noncoenzyme A-dependent mechanism.

Animals↗
PubMed1992

Recovery of protein by coomassie brilliant blue precipitation prior to electrophoresis.

The interaction of protein with Coomassie Brilliant Blue G-250 results in formation of an insoluble protein-dye complex which can be recovered by centrifugation and redissolved for electrophoretic analysis. The precipitated protein can be washed in acetone to remove excess dye in order to enhance resolution. The residual dye becomes dissociated from the proteins on electrophoresis and can be exploited as a "dye front". The method allows simultaneous protein assay and recovery of microgram amounts of protein from dilute solution and could be widely applied for conserving, concentrating and desalting minute amounts of valuable sample prior to electrophoretic analysis.

Chemical Precipitation↗
PubMed1992

Coomassie blue protein dye-binding assays measure formation of an insoluble protein-dye complex.

The solubility of the protein-Coomassie brilliant blue (CBB) complex formed upon Bradford (Anal. Biochem. 72, 248-254, 1976) or Sedmak and Grossberg (Anal. Biochem. 79, 544-552, 1977) protein assay has been investigated by centrifugation or filtration of the assay mix within 10 min of adding dye reagent. The results show complete loss of color yield in the respective supernates and filtrates. This indicates that the protein-CBB complexes are insoluble at the time of absorbance measurement. Protein solubility in the dye reagent may dictate the relative response of the assay to an individual protein and the requirement for macromolecular structure.

Animals↗