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Biomedical subjects

G Hughes

Publications and source records attributed to G Hughes.

At least 73 records · Page 4Linked to original sources
PubMed2000

Investigation of the increased incidence of gonorrhoea diagnosed in genitourinary medicine clinics in England, 1994-6.

OBJECTIVES: To determine important risk factors associated with cases of gonorrhoea in England, and whether any particular risk groups were associated with the substantial rise in numbers of cases seen between 1994 and 1996. DESIGN: Two retrospective cross sectional surveys. SETTING: 70 randomly selected genitourinary medicine (GUM) clinics in England. SUBJECTS: 10% of all gonorrhoea patients attending GUM clinics in England in 1994 (847 patients) and 1996 (1146 patients). MAIN OUTCOME MEASURES: For risk factors in 1996 (study 1), unadjusted rates per 100,000 population aged 14-70 and relative rates (RR) with 95% confidence intervals (CIs). For the change in risk factors between 1994 and 1996 (study 2), adjusted odds ratios (ORs) with 95% CIs, derived from logistic regression analyses of data on patients in 1996, with patients in 1994 as the comparison group. RESULTS: The incidence of gonorrhoea in 1996 was higher in homosexual males (812 per 100,000; RR = 30.2, CI = 25.2 to 36.0) compared with heterosexual males (27 per 100,000); in black Caribbeans (467 per 100,000; 21.4, 17.9 to 25.5) and black Africans (235 per 100,000; 10.8, 7.5 to 15.5) compared with white people (22 per 100,000); and in previous GUM clinic attenders (433 per 100,000; 37.93, 35.46 to 40.56) compared with those who had not attended previously (11 per 100,000). However, most patients were either white or heterosexual. Heterosexual patients in 1996 were significantly more likely to have reduced sensitivity to penicillin (2.55, 1.20 to 5.41) than those in 1994. Male homo/bisexual patients in 1996 were significantly more likely to be from the north west (3.77, 1.45 to 9.80) and to have either reduced sensitivity (2.63, 1.03 to 6.73) or complete resistance (1.98, 1.03 to 3.78) to penicillin, compared with those in 1994. CONCLUSIONS: Homo/bisexual men and the black Caribbean population in England experience a disproportionate burden of gonococcal infections, however, the bulk of diagnoses are in white heterosexuals. No single risk group was associated with the rise in numbers of cases between 1994 and 1996. Resistance to penicillin is widespread and has increased in homo/bisexual men, and it is possible that a rise in treatment failures has, to some extent, enhanced transmission of gonorrhoea and contributed to the rise in numbers of diagnoses in this group.

Adolescent↗
PubMed2000

Comparison of risk factors for four sexually transmitted infections: results from a study of attenders at three genitourinary medicine clinics in England.

OBJECTIVE: To compare the risk factors for four common sexually transmitted infections (STIs) in attenders at three large urban genitourinary medicine (GUM) clinics in England. METHODS: Clinical, demographic, and behavioural data on attenders at two clinics in London and one in Sheffield were collected. Risk factors associated with first episodes of genital warts and genital herpes simplex virus (HSV), and uncomplicated gonorrhoea and chlamydia were investigated using the presence of each of these STIs as the outcome variable in separate multiple logistic regression analyses. RESULTS: Using data on the first attendance of the 18,238 patients attending the clinics in 1996, the risk of a gonorrhoea or chlamydia diagnosis was strongly associated with teenagers compared with those aged over 34, with black Caribbeans and black Africans compared with whites, and increased with the number of sexual partners. The risk of genital warts or HSV diagnosis was lowest in black Caribbeans and black Africans compared with whites and was not associated with the number of sexual partners. While genital warts were associated with younger age, odds ratios were much lower compared with those for the bacterial infections. Genital HSV diagnoses were not associated with age. CONCLUSIONS: This study of GUM clinic attenders suggests a reduction in the incidence of bacterial STIs may be achievable through targeted sexual health promotion focusing particularly on black ethnic minorities, teenagers, and those with multiple sexual partnerships. Viral STIs were less clearly associated with population subgroups and a broader population based approach to sexual health promotion may be more effective in controlling these infections.

Adolescent↗
PubMed1999

Increased stability upon heptamerization of the pore-forming toxin aerolysin.

Aerolysin is a bacterial pore-forming toxin that is secreted as an inactive precursor, which is then processed at its COOH terminus and finally forms a circular heptameric ring which inserts into membranes to form a pore. We have analyzed the stability of the precursor proaerolysin and the heptameric complex. Equilibrium unfolding induced by urea and guanidinium hydrochloride was monitored by measuring the intrinsic tryptophan fluorescence of the protein. Proaerolysin was found to unfold in two steps corresponding to the unfolding of the large COOH-terminal lobe followed by the unfolding of the small NH(2)-terminal domain. We show that proaerolysin contains two disulfide bridges which strongly contribute to the stability of the toxin and protect it from proteolytic attack. The stability of aerolysin was greatly enhanced by polymerization into a heptamer. Two regions of the protein, corresponding to amino acids 180-307 and 401-427, were identified, by limited proteolysis, NH(2)-terminal sequencing and matrix-assisted laser desorption ionization-time of flight, as being responsible for stability and maintenance of the heptamer. These regions are presumably involved in monomer/monomer interactions in the heptameric protein and are exclusively composed of beta structure. The stability of the aerolysin heptamer is reminiscent of that of pathogenic, fimbrial protein aggregates found in a variety of neurodegenerative diseases.

Amino Acid Sequence↗
PubMed1999

Purification, characterization, DNA sequence and cloning of a pimeloyl-CoA synthetase from Pseudomonas mendocina 35.

A pimeloyl-CoA synthetase from Pseudomonas mendocina 35 was purified and characterized, the DNA sequence determined, and the gene cloned into Escherichia coli to yield an active enzyme. The purified enzyme had a pH optimum of approximately 8.0, Km values of 0.49 mM for pimelic acid, 0.18 mM for CoA and 0.72 mM for ATP, a subunit Mr of approximately 80000 as determined by SDS/PAGE, and was found to be a tetramer by gel-filtration chromatography. The specific activity of the purified enzyme was 77.3 units/mg of protein. The enzyme was not absolutely specific for pimelic acid. The relative activity for adipic acid (C6) was 72% and for azaleic acid (C9) was 18% of that for pimelic acid (C7). The N-terminal amino acid was blocked to amino acid sequencing, but controlled proteolysis resulted in three peptide fragments for which amino acid sequences were obtained. An oligonucleotide gene probe corresponding to one of the amino acid sequences was synthesized and used to isolate the gene (pauA, pimelic acid-utilizing A) coding for pimeloyl-CoA synthetase. The pauA gene, which codes for a protein with a theoretical Mr of 74643, was then sequenced. The deduced amino acid sequence of the enzyme showed similarity to hypothetical proteins from Archaeoglobus fulgidus, Methanococcus jannaschii, Pyrococcus horikoshii, E. coli and Streptomyces coelicolor, and some limited similarity to microbial succinyl-CoA synthetases. The similarity with the protein from A. fulgidus was especially strong, thus indicating a function for this unidentified protein. The pauA gene was cloned into E. coli, where it was expressed and resulted in an active enzyme.

Acyl Coenzyme A↗
PubMed1999

2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2 inhibitors.

Cyclopentenones containing a 4-(methylsulfonyl)phenyl group in the 3-position and a phenyl ring in the 2-position are selective inhibitors of cyclooxygenase-2 (COX-2). The selectivity for COX-2 over COX-1 is dramatically improved by substituting the 2-phenyl group with halogens in the meta position or by replacing the phenyl ring with a 2- or 3-pyridyl ring. Thus the 3,5-difluorophenyl derivative 7 (L-776,967) and the 3-pyridyl derivative 13 (L-784,506) are particularly interesting as potential antiinflammatory agents with reduced side-effect profiles. Both exhibit good oral bioavailability and are potent in standard models of pain, fever, and inflammation yet have a much reduced effect on the GI integrity of rats compared to standard nonsteroidal antiflammatory drugs.

Analgesics, Non-Narcotic↗
PubMed1999

Ability of Proteus mirabilis to swarm over urethral catheters.

The aim of this study was to investigate the ability of Proteus mirabilis to swarm over various types of urinary catheters. The test strain was found to swarm over catheters for distances of up to 10 cm within 24 h. Migration was significantly more rapid over hydrogel-coated latex catheters than over all-silicone or silicone-coated latex catheters. Scanning electron micrographs revealed discrete rafts of typically elongated swarmer cells on catheter surfaces. Migration of swarmers along catheters into the bladder could thus initiate Proteus mirabilis catheter-associated infections.

Catheters, Indwelling↗
PubMed1999

Quantitation and origin of the mitochondrial membrane potential in human cells lacking mitochondrial DNA.

Mammalian mitochondrial DNA (mtDNA) encodes 13 polypeptide components of oxidative phosphorylation complexes. Consequently, cells that lack mtDNA (termed rho degrees cells) cannot maintain a membrane potential by proton pumping. However, most mitochondrial proteins are encoded by nuclear DNA and are still imported into mitochondria in rho degrees cells by a mechanism that requires a membrane potential. This membrane potential is thought to arise from the electrogenic exchange of ATP4- for ADP3- by the adenine nucleotide carrier. An intramitochondrial ATPase, probably an incomplete FoF1-ATP synthase lacking the two subunits encoded by mtDNA, is also essential to ensure sufficient charge flux to maintain the potential. However, there are considerable uncertainties about the magnitude of this membrane potential, the nature of the intramitochondrial ATPase and the ATP flux required to maintain the potential. Here we have investigated these factors in intact and digitonin-permeabilized mammalian rho degrees cells. The adenine nucleotide carrier and ATP were essential, but not sufficient to generate a membrane potential in rho degrees cells and an incomplete FoF1-ATP synthase was also required. The maximum value of this potential was approximately 110 mV in permeabilized cells and approximately 67 mV in intact cells. The membrane potential was eliminated by inhibitors of the adenine nucleotide carrier and by azide, an inhibitor of the incomplete FoF1-ATP synthase, but not by oligomycin. This potential is sufficient to import nuclear-encoded proteins but approximately 65 mV lower than that in 143B cells containing fully functional mitochondria. Subfractionation of rho degrees mitochondria showed that the azide-sensitive ATPase activity was membrane associated. Further analysis by blue native polyacrylamide gel electrophoresis (BN/PAGE) followed by activity staining or immunoblotting, showed that this ATPase activity was an incomplete FoF1-ATPase loosely associated with the membrane. Maintenance of this membrane potential consumed about 13% of the ATP produced by glycolysis. This work has clarified the role of the adenine nucleotide carrier and an incomplete FoF1-ATP synthase in maintaining the mitochondrial membrane potential in rho degrees cells.

Adenosine Triphosphatases↗
PubMed1999

ATLS: are we training the wrong people?

BACKGROUND: Despite the evolution, expansion and popularity of emergency medicine as a medical specialty in the United Kingdom (UK), emergency departments are still primarily staffed by senior house officers (second and third year graduates), particularly at weekends and at night. METHODS: A telephone and postal survey of Advanced Trauma Life Support (ATLS) training completed by this cohort of doctors indicates that UK courses are failing to train adequate numbers. RESULTS: It can thus be argued that ATLS is not being disseminated to the relevant grass-roots of medical care, where it is likely to be of the most benefit. CONCLUSIONS: The present study discusses possible reasons for this and offers constructive solutions to the problem. Although the matters discussed in this study refer to UK medical practice, they may be of relevance and interest to Australasian practitioners. Is EMST in Australasia training the appropriate group of doctors?

Data Collection↗