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Biomedical subjects

R Parry

Publications and source records attributed to R Parry.

At least 19 recordsLinked to original sources
PubMed1998

Biosynthesis of the Pseudomonas polyketide coronafacic acid requires monofunctional and multifunctional polyketide synthase proteins.

Coronafacic acid (CFA) is the polyketide component of the phytotoxin coronatine, a virulence factor of the plant pathogen Pseudomonas syringae. Our current knowledge of polyketide biosynthesis largely is based on the analysis of polyketide synthases (PKSs) in actinomycetes and other Gram-positive bacteria. Consequently, the cloning and characterization of the CFA biosynthetic gene cluster will contribute significantly to our knowledge of polyketide synthesis in Pseudomonas. In this report, we describe two genes in the CFA biosynthetic gene cluster that encode PKSs that are structurally and functionally similar to the multifunctional modular PKSs, which catalyze the synthesis of macrolide antibiotics. The CFA PKS genes were overproduced in Escherichia coli and shown to cross-react with antisera made to a modular PKS involved in erythromycin synthesis. A scheme for CFA biosynthesis is presented that incorporates the activities of all proteins in the CFA PKS. In this report a gene cluster encoding a pseudomonad polyketide has been completely sequenced and the deduced gene functions have been used to develop a biosynthetic scheme.

Actinomycetales↗
PubMed1998

The impact of initial surgical management on outcome in young patients with differentiated thyroid cancer.

BACKGROUND/PURPOSE: It is generally believed that differentiated thyroid cancer (DTC) in young patients has an excellent prognosis. This calls into question the need for more extensive surgical ablation of the thyroid gland with attendant risks of surgical complications. The purpose of this report was to investigate both the incidence of surgical morbidity and the impact of surgery on locoregional recurrence of disease. METHODS: The authors reviewed the clinical course of patients under 22 years of age treated for DTC within Department of Defense hospitals since 1950. Data were available for determination of surgical morbidity in 126 and for outcome in 105. RESULTS: The incidence of postoperative hypocalcemia was 17% and of recurrent laryngeal nerve injury 3%. Factors predictive of morbidity were (1) more extensive thyroid surgery (P = .023), and (2) the presence of gross tumor invasion (P = .022). The incidence of neck recurrence was analyzed among a cohort of 90 patients. A total of 19 (21%) patients had a local recurrence. The median time to recurrence was 24 months. The factor predictive of recurrence was the presence of gross invasion (P = .0001). A strong trend toward locoregional recurrence was found among patients with metastatic disease to more than five cervical nodes (P < .08). The primary operations on the thyroid and regional nodes were not significant predictors of neck recurrence. Among these 19 patients there have been no deaths, but 25% had persistent disease at a mean follow-up of 12.6 years. CONCLUSIONS: The incidence of surgical morbidity does increase with more extensive surgery. Outcome is predicted primarily by the initial extent of disease.

Adolescent↗
PubMed1998

Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma.

Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heterogeneous. To identify genes that influence asthma and asthma-associated phenotypes, we conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry. A primary sample of 361 individuals and a replication sample of 292 individuals were evaluated for asthma phenotypes according to a standardized protocol. A genome-wide screen has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio chi2 test and the transmission-disequilibrium test, we identified 12 markers in 10 regions that showed possible linkage to asthma or an associated phenotype (likelihood ratio P < 0.01). Markers in four regions (5q23-31, 12q15-24.1, 19q13 and 21q21) showed possible linkage in both the primary and replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24.2-22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility alleles at many loci may influence asthma phenotypes and that these susceptibility alleles are likely to be common polymorphisms in the population.

Adolescent↗
PubMed1998

Silicon and aluminium interactions in haemodialysis patients.

BACKGROUND: Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity. METHODS: We measured serum aluminium and silicon levels from haemodialysis patients from four different centres. RESULTS: Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) micromol/l when serum silicon was less than 150 micromol/l, and lower, 1.1 (0.2-2.8) micromol/l when serum silicon levels were greater than 150 micromol/l (P = 0.03). CONCLUSIONS: In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.

Aluminum↗
PubMed1997

Expression and analysis of coronafacate ligase, a thermoregulated gene required for production of the phytotoxin coronatine in Pseudomonas syringae.

Coronafacic acid, the polyketide component of the phytotoxin coronatine, is activated and coupled to coronamic acid via amide bond formation, a biosynthetic step presumably catalyzed by the coronafacate ligase (cfl) gene product. In the present study, cfl was fused to the carboxy terminus of malE, which encodes the maltose-binding protein (MBP), and overexpressed in Escherichia coli. Immunoblot analysis indicated that Cfl contained an ATP-binding region, a motif conserved in enzymes which activate their substrates by adenylation. MBP-Cfl was overproduced and purified from Pseudomonas syringae and the protein fusion was used to generate antisera. Anti-MBP-Cfl antibodies and a transcriptional fusion of the cfl promoter to a promoterless glucuronidase gene were used to follow the temporal expression of coronafacate ligase. The results indicated that transcription of cfl is temperature-sensitive. Furthermore, a nonpolar mutation in cfl suggested that the gene may have a role in coronafacic acid biosynthesis.

Amide Synthases↗
PubMed1996

Evaluation of distal run-off before femorodistal bypass.

The quality of distal run-off is one of the most important factors in determining outcome of femorodistal bypass. Accurate evaluation is important. Preoperative intra-arterial digital subtraction angiography and Doppler evaluation with pulse-generated augmentation of 90 patients who underwent femorodistal reconstruction were compared with postoperative angiography. Underestimation of distal run-off of the calf vessels occurred in 33% of cases by preoperative intra-arterial digital subtraction angiography. A below-knee pulse-generated run-off score of 3 or less was associated with a 12-month cumulative patency of 73% compared with 85% with a below-knee pulse-generated run-off score of 4 or more (P=0.079, log rank test; P =0.060, Wilcoxon signed rank test). The 12-month cumulative patency for grafts with a complete, incomplete and occluded arch as defined by pulse-generated run-off was 78, 90 and 38% respectively (P<0.0001 log rank and Wilcoxon signed rank tests). Preoperative evaluation of distal run-off before femorodistal bypass should not be based exclusively on intra-arterial digital subtraction angiography.

Aged↗
PubMed1996

Inhibition of sperm-zona binding by suramin, a potential 'lead' compound for design of new anti-fertility agents.

Progress in developing new contraceptive agents, particularly for the male, is extremely slow. Here, we report on a novel property of the anti-trypanosomal drug suramin: the ability to act at the sperm-egg interface and prevent fertilization. Suramin is a polysulphonated compound that inhibits binding of capacitated mouse spermatozoa to the zona pellucida in vitro with an IC50 of 12.4 microM. The drug is only effective at the time of fertilization and is not inhibitory if gametes are pre-treated separately. Autoradiographic localization of suramin binding sites on mouse, boar and human spermatozoa shows that they are intracellular, principally in the head region. The sperm protein recognized by suramin has been identified as proacrosin which is known to interact with sulphate groups on zona glycoproteins. Zona pellucida glycoproteins do not bind suramin, suggesting that the drug blocks the ability of proacrosin/acrosin, exposed during the acrosome reaction, to mediate the secondary binding phase of spermatozoa to the zona during fertilization. Structure-based design studies have the potential to generate safe suramin mimetics that would form the basis for a new generation of non-steroidal contraceptive agents.

Acrosin↗
PubMed1995

Antibody ligation of CD7 leads to association with phosphoinositide 3-kinase and phosphatidylinositol 3,4,5-trisphosphate formation in T lymphocytes.

The CD7 40-kDa glycoprotein is present on a major subset of human T cells and in the presence of phorbol esters mediates an accessory pathway of T cell activation. Hitherto, the intracellular events elicited by CD7 have been ill-defined. This report demonstrates that cross-linking of CD7 results in the formation of phosphatidic acid in the absence of phosphatidylinositol-4,5-bisphosphate metabolism and also the formation of D-3 phosphoinositides lipids which have been postulated to act as intracellular regulatory molecules. The magnitude of D-3 phosphoinositide formation was similar to that induced by CD3. Both the CD7- and CD3-induced elevation of phosphatidylinositol 3,4,5-trisphosphate approximately 5-10 fold less than that elicited by ligation of the costimulatory molecule CD28 by its counter receptor CD80. The formation of D-3 phosphoinositides following ligation of CD7 coincided with the co-association of CD7 with phosphoinositide 3-kinase, the enzyme which mediates the formation of D-3 phosphoinositide lipids. In contrast, ligation of another reported T cell accessory molecule CD5, failed to elicit formation of D-3 phosphoinositides, implying that phosphoinositide 3-kinase is not coupled to all T cell molecules with accessory functions. Since D-3 phosphoinositides have been suggested to play a pivotal role in T cell costimulatory signals induced by CD28, the results presented in this study suggest that CD7 may also influence T cell activation via this pathway.

Androstadienes↗
PubMed1995

Chaos under canvas: a Salmonella enteritidis PT 6B outbreak.

An outbreak of Salmonella enteritidis PT 6B food poisoning, the first reported of this recently described phage type, resulted in illness among 46 of 49 members of a camping group in North Wales, 33 of whom were hospitalized. Epidemiological evidence (P < 0.0001) indicated that a lemon meringue pie was the vehicle of infection. Fresh shell eggs, stored after purchase at ambient temperature, appear to be the most likely source of infection, with multiplication during preparation and subsequent storage of the pie a significant contributory factor. Campers may be at greater risk than others and should consider the use of cold boxes for the transport and storage of eggs, and avoid the preparation of lightly cooked egg products under these basic conditions.

Abdominal Pain↗
PubMed1994

Case report: spontaneous coronary artery dissection.

Spontaneous coronary artery dissection is a rare cause of ischaemic heart disease occurring most commonly in young women. It is frequently fatal. Our case is unusual in that a very long dissection flap was diagnosed by coronary angiography in a male patient who presented with only minor symptoms. We discuss the pathogenesis of spontaneous dissection and the prognosis for this group of patients.

Adult↗
PubMed1993

Angiographic prediction of dissection followed by ischaemic complications during coronary angioplasty.

Ischaemic problems occur in about 8% of coronary angioplasties and are the major cause of morbidity and mortality associated with the procedure. Although the ischaemic event is usually due to acute vessel closure due to vessel dissection, it is noteworthy that 80-90% of radiographically visible dissections cause no problem. We have reviewed 200 consecutive coronary angioplasties in order to find predictive factors for those patients likely to suffer dissection followed by ischaemic complications. Thirty-four (17%) of the patients undergoing coronary angioplasty had radiographically visible dissections, of whom 12 (35%) suffered ischaemic complications. There were 16 (8%) major ischaemic complications following angioplasty. In four of these cases no obvious dissection was visible within the vessel. Eight out of a subgroup of 16 patients who had sequential stenoses along one vessel dilated at angioplasty had a dissection. Six of these eight patients suffered a major ischaemic complication following the dissection. Thus in this group of patients, sequential stenosis not only conferred a high probability of dissection during angioplasty but additionally carried an increased risk of ischaemic complications following the dissection. Awareness of this may affect case selection and may indicate the need for early re-examination of the vessel should problems occur following angioplasty.

Aortic Dissection↗