PubMed Health⌕ Search

Biomedical subjects

J Beynon

Publications and source records attributed to J Beynon.

At least 37 records · Page 2Linked to original sources

Crystallization and preliminary X-ray analysis of tetracenomycin A2 oxygenase: a flavoprotein hydroxylase involved in polyketide biosynthesis.

The tcm operon in Streptomyces glaucescens encodes a group of enzymes involved in the synthesis of the polyketide tetracenomycin (Tcm) C that exhibits both antitumor and antibiotic activities. Here, the crystallization and preliminary data characterization of the tcmG gene product, Tcm A2 oxygenase, which catalyzes the triple hydroxylation of Tcm A2 to form Tcm C, are reported. Tcm A2 oxygenase crystallizes in two different space groups, both with six monomers per asymmetric unit, resulting in large unit-cell parameters. Synchrotron data have been collected from both the hexagonal and tetragonal crystal forms to 4.5 and 4.2 A, respectively. The self-rotation function searches in both space groups suggest the monomers assemble into a complex with D(3) symmetry.

Anthracyclines↗

Genetic and physical mapping of the RPP13 locus, in Arabidopsis, responsible for specific recognition of several Peronospora parasitica (downy mildew) isolates.

Fifteen isolates of the biotrophic oomycete Peronospora parasitica (downy mildew) were obtained from a population of Arabidopsis thaliana plants that established naturally in a garden the previous year. They exhibited phenotypic variation in a set of 12 Arabidopsis accessions that suggested that the parasite population consisted of at least six pathotypes. One isolate, Maks9, elicited an interaction phenotype of flecking necrosis and no sporulation (FN) in the Arabidopsis accession Nd-1, and more extensive pitting necrosis with no sporulation (PN) in the accession Ws-2. RPP13 was designated as the locus for a single dominant resistance gene associated with the resistance in Nd-1 and mapped to an interval of approximately 60 kb on a bacterial artificial chromosome (BAC) contig on the lower arm of chromosome 3. This locus is approximately 6 cM telomeric to RPP1, which was previously described as the locus for the PN interaction with five Peronospora isolates, including resistance to Maks9 in Ws-2. New Peronospora isolates were obtained from four other geographically distinct populations of P. parasitica. Four isolates were characterized that elicited an FN phenotype in Nd-1 and mapped resistance to the RPP13 locus. This suggests that the RPP13 locus contains either a single gene capable of multiple isolate recognition or a group of tightly linked genes. Further analysis suggests that the RPP11 gene in the accession Rld-0 may be allelic to RPP13 but results in a different recognition capability.

Alleles↗

Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity.

BACKGROUND: Bile acid toxicity has been shown in the gastric, colonic, and hepatic tissues; the effect on oesophageal mucosa is less well known. AIMS: To determine the spectrum of bile acids refluxing in patients with gastro-oesophageal reflux disease and its relation to oesophageal pH using a new technique of combined oesophageal aspiration and pH monitoring. METHODS: Ten asymptomatic subjects and 30 patients with symptoms of gastro-oesophageal reflux disease (minimal mucosal injury, erosive oesophagitis (grade 2 or 3 Savary-Miller), Barrett's oesophagus/stricture; n=10 in each group) underwent 15 hour continuous oesophageal aspiration with simultaneous pH monitoring. Bile acid assay of the oesophageal samples was performed using modified high performance liquid chromatography. RESULTS: The peak bile acid concentration and DeMeester acid scores were significantly higher in the patients with oesophagitis (median bile acid concentration 124 micromol/l; acid score 20.2) and Barrett's oesophagus/stricture (181 micromol/l; 43. 3) than patients with minimal injury (14 micromol/l; 12.5) or controls (0 micromol/l; 11.1). The predominant bile acids detected were cholic, taurocholic, and glycocholic acids but there was a significantly greater proportion of secondary bile acids, deoxycholic and taurodeoxycholic acids, in patients with erosive oesophagitis and Barrett's oesophagus/stricture. Although bile acid reflux episodes occurred at variable pH, a temporal relation existed between reflux of taurine conjugates and oesophageal acid exposure (r=0.58, p=0.009). CONCLUSION: Toxic secondary bile acid fractions have been detected in patients with extensive mucosal damage. Mixed reflux is more harmful than acid reflux alone with possible toxic synergism existing between the taurine conjugates and acid.

Adult↗

Assessment of combined bile acid and pH profiles using an automated sampling device in gastro-oesophageal reflux disease.

BACKGROUND: Bile acid reflux is an important component of duodenogastro-oesophageal reflux but there is no effective method of quantifying it. The contribution of bile acids to oesophageal pH is unknown. METHODS: Oesophageal aspirates were collected over 15 h using a new automated suction device and pH was monitored in ten asymptomatic volunteers (group 1) and 30 patients with reflux oesophagitis (group 2, minimal mucosal injury; group 3, erosive oesophagitis; group 4, stricture or Barrett's oesophagus). Bile acid assay was performed by high-performance liquid chromatography. RESULTS: The concentration of bile acids was significantly higher in group 3 (median (interquartile range) 124 (50-301) mumol/l) and group 4 (181 (85-591) mumol/l) compared with group 1 (0 mumol/l) and group 2 (14 (0-100) mumol/l). Patients in groups 3 and 4 also had significantly greater DeMeester acid scores. Combined bile acid and oesophageal acid reflux was observed in eight of ten patients with stricture or Barrett's oesophagus. There was no correlation between total bile acid concentration and oesophageal acid or alkaline exposure. CONCLUSION: This study supports the theory of toxic synergism between acid and bile acids in reflux oesophagitis. Bile acids may contribute to the pathogenesis of Barrett's metaplasia.

Adult↗

Anal endosonography in patients with anorectal symptoms after haemorrhoidectomy.

BACKGROUND: Anorectal symptoms after haemorrhoidectomy are common and treatment is often empirical. Because of this, an audit was carried out of the value of anal endosonography in patients with anorectal symptoms after haemorrhoidectomy. METHODS: Between May 1993 and February 1997, 16 patients (ten men and six women of median age 56 (range 35-77) years) were investigated by anal endosonography for anorectal symptoms after haemorrhoidectomy which involved anorectal incontinence (n = 10), anal pain (n = 4) and obstructive defaecation (n = 2). The findings were compared with those in a matched group of asymptomatic patients after haemorroidectomy. RESULTS: Anal endosonography demonstrated an abnormality in 12 symptomatic patients. Of the ten patients with anorectal incontinence, endosonography showed an internal anal sphincter defect (n = 5), a combined sphincter defect (n = 2) and an isolated external anal sphincter defect (n = 1). Normal appearances were seen in all asymptomatic patients. The endosonographic abnormalities of the four patients with anal pain included internal anal sphincter defect (n = 1), extrinsic mass (n = 1), and intersphincteric abscess (n = 1). One of the two patients with obstructive defaecation had an isolated external anal sphincter defect on endosonography. CONCLUSION: These results show a high yield of endosonographic abnormalities in patients who experience symptoms after haemorrhoidectomy. In particular, occult sphincter injury as a cause of incontinence in these patients can frequently be demonstrated.

Adult↗

Differential expression of a senescence-enhanced metallothionein gene in Arabidopsis in response to isolates of Peronospora parasitica and Pseudomonas syringae.

The metallothionein gene, LSC54, shows increased expression during leaf senescence in Brassica napus and Arabidopsis thaliana. A number of abiotic and biotic stresses have been shown to induce senescence-like symptoms in plants and, to investigate this further, the promoter of the LSC54 gene was cloned and fused to the GUS gene and transformed into Arabidopsis. The promoter was highly induced during leaf senescence and also in response to wounding; histochemical analysis indicated that this induction was localised to a few cells close to the wound site. The transgenic Arabidopsis tissue was infected with compatible and incompatible isolates of both the fungal biotroph, Peronospora parasitica and the bacterial necrotroph, Pseudomonas syringae. Incompatible isolates induced rapid cell death (the hypersensitive response) at the site of infection and, with both pathogens, early, localised expression of the GUS gene was observed. In contrast, relatively slow induction of the GUS gene was seen in the compatible interaction and this was correlated with the appearance of senescence-like symptoms in the biotrophic interaction and cell death by necrosis that occurred in response to the necrotrophic pathogen. These results suggest that there are common steps in the signalling pathways that lead to cell death in the hypersensitive response, pathogen induced necrosis and senescence.

Arabidopsis↗

Genetic characterization of RRS1, a recessive locus in Arabidopsis thaliana that confers resistance to the bacterial soilborne pathogen Ralstonia solanacearum.

The soilborne, vascular pathogen Ralstonia solanacearum, the causative agent of bacterial wilt, was shown to infect a range of Arabidopsis thaliana accessions. The pathogen was capable of infecting the Col-5 accession in an hrp-dependent manner, following root inoculation. Elevated bacterial population levels were found in leaves of Col-5, 4 to 5 days after root inoculation by the GMI1000 strain. Bacteria were found predominantly in the xylem vessels and spread systematically throughout the plant. The Nd-1 accession of A. thaliana was resistant to the GMI1000 strain of R. solanacearum. Bacterial concentrations detected in leaves of Nd-1, inoculated with an hrp+ strain of R. solanacearum, were only slightly higher than those detected in the susceptible accession, Col-5, following inoculation with a strain whose hrp gene cluster was deleted. Leaf inoculation of the GMI1000 strain on the resistant accession Nd-1 induced the formation of lesions in the older leaves of the rosette whereas the same strain of R. solanacearum provoked complete wilting of Col-5. Resistance to strain GMI1000 of R. solanacearum segregated as a simply inherited recessive trait in a genetic cross between Col-5 and Nd-1. F9 recombinant inbred lines generated between these two accessions were used to map a locus, RRS1, that was the major determinant of resistance between restriction fragment length polymorphism markers mi83 and mi61 on chromosome V. This region of the A. thaliana genome is known to contain many other pathogen recognition capabilities.

Arabidopsis↗

Evaluating an osteoporosis service using a focus group.

Evaluation of any service should determine whether the service meets patients' perceived needs as well as their identified medical needs. This article describes the use of a focus group to evaluate a service for women with a diagnosis of osteoporosis.

Aged↗

Enoxaparin, a low-molecular-weight heparin suppresses prothrombin activation more effectively than unfractionated heparin in patients treated for venous thromboembolism.

Although unfractionated heparin (UFH) is standard therapy for venous thromboembolism, there is a clinical failure rate of up to 10%. Newer treatment strategies include low-molecular-weight heparins (LMWH). As part of an international study comparing the efficacy and safety of enoxaparin, a LMWH versus UFH in patients with venous thromboembolism, we studied the effects of enoxaparin and UFH on the plasma concentrations of two activation peptides, fragment 1 + 2 (F1 + 2), and thrombin-antithrombin III (TAT) complexes. We hypothesized that enoxaparin would be more effective in suppressing activation of coagulation. Intravenous heparin was given by bolus injection followed by infusion. There were 2 enoxaparin treatment groups (1 mg/kg s.c., bid and 1.5 mg/kg s.c. daily). Plasma samples were obtained from 11 patients in the enoxaparin group and 6 patients in the heparin group prior to and at 6 hour intervals after initiating therapy. Clinical characteristics of the enoxaparin and UFH patient groups were similar. TAT concentrations were not statistically different between groups at any treatment interval. However, plasma F1 + 2 concentrations differed significantly (p < 0.05); concentrations in the enoxaparin group were consistently lower over time than in the UFH group. These results suggest that this LMWH is more effective in suppressing ongoing thrombosis in vivo than UFH in patients with venous thrombosis.

Adult↗

Surgical management of anorectal incontinence due to internal anal sphincter deficiency.

BACKGROUND: The aetiology, surgical management and outcome in 15 patients with anorectal incontinence due to internal and sphincter (IAS) deficiency as a result of previous anal surgery (n = 14) or penetrating trauma (n = 1) was studied. METHODS: The degree of anorectal incontinence was scored by the Cleveland Clinic system; median score was 14 (range 11-16) before surgery. In all patients the anal sphincter mechanism was assessed by endoanal ultrasonography. Thirteen of the 15 patients underwent either rotation (n = 5), island (n = 5) or advancement (n = 3) anoplasty to correct the contour defect in the anal canal. In the remaining two patients direct IAS repair was performed. RESULTS: Four of the 13 patients who underwent anoplasty developed wound breakdown as the result of infection (n = 3) or inadvertent suture removal (n = 1). A defunctioning stoma was required in three of these patients but all of these have been closed. At median follow-up of 34 (range 6-72) months, all patients who underwent anoplasty have normal defaecatory control and a median continence score of 2 (range 0-4). Direct IAS repair produced no symptomatic improvement in either patient. CONCLUSION: These results suggest that anoplasty deserves further evaluation in the treatment of anorectal incontinence due to discrete IAS defects, but that the place of IAS repair remains uncertain.

Adult↗