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Biomedical subjects

A Preston

Publications and source records attributed to A Preston.

At least 19 recordsLinked to original sources
PubMed2004

A1 and A2A adenosine receptor modulation of alpha 1-adrenoceptor-mediated contractility in human cultured prostatic stromal cells.

1. This study investigated the possibility that adenosine receptors modulate the alpha(1)-adrenoceptor-mediated contractility of human cultured prostatic stromal cells (HCPSC). 2. The nonselective adenosine receptor agonist, 5'-N-ethylcarboxamido-adenosine (NECA; 10 nm-10 microm), and the A(1) adenosine receptor selective agonist, cyclopentyladenosine (CPA; 10 nm-10 microm), elicited significant contractions in HCPSC, with maximum contractile responses of 18+/-3% and 17+/-2% reduction in initial cell length, respectively. 3. In the presence of a threshold concentration of phenylephrine (PE) (100 nm), CPA (1 nm-10 microm) caused contractions, with an EC(50) of 124+/-12 nm and maximum contractile response of 37+/-4%. The A(1) adenosine receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX 100 nm) blocked this effect. In the presence of DPCPX (100 nm), NECA (1 nm-10 microm) inhibited contractions elicited by a submaximal concentration of PE (10 microm), with an IC(50) of 48+/-2 nm. The A(2A) adenosine receptor-selective antagonist 4-(2-[7-amino-2-[furyl][1,2,4]triazolo[2,3-alpha][1,3,5,]triazin-5-yl amino]ethyl)phenol (Zm241385 100 nm) blocked this effect. 4. In BCECF-AM (10 microm)-loaded cells, both CPA (100 pM-1 microm) and NECA (100 pm-10 microm) elicited concentration-dependent decreases in intracellular pH (pH(i)), with EC(50) values of 3.1+/-0.3 and 6.0+/-0.3 nm, respectively. The response to NECA was blocked by Zm241385 (100 nm; apparent pK(B) of 9.4+/-0.4), but not by DPCPX (100 nm). The maximum response to CPA was blocked by DPCPX (100 nm), and unaffected by Zm241385 (100 nm). 5. NECA (10 nm-10 microm) alone did not increase [(3)H]-cAMP in HCPSC. In the presence of DPCPX (100 nm), NECA (10 nm-10 microm) caused a concentration dependent increase in [(3)H]-cAMP, with an EC(50) of 1.2+/-0.1 microm. This response was inhibited by Zm241385 (100 nm). CPA (10 nm-10 microm) had no effect on cAMP, in the presence or absence of forskolin (1 microm). 6. These findings are consistent with a role for adenosine receptors in the modulation of adrenoceptor-mediated contractility in human prostate-derived cells.

Adenosine A1 Receptor Agonists↗
PubMed2003

Alpha 1-adrenoceptor effects mediated by protein kinase C alpha in human cultured prostatic stromal cells.

1 We have investigated the effects of alpha(1)-adrenoceptor stimulation upon contractility, Ca(2+) influx, inositol phosphate production, and protein kinase C (PKC) translocation in human cultured prostatic stromal cells (HCPSC). 2 The alpha(1)-adrenoceptor selective agonist phenylephrine elicited contractile responses of HCPSC, i.e. a maximal cell shortening of 45+/-6% of initial cell length, with an EC(50) of 1.6+/-0.1 microM. The alpha(1)-adrenoceptor selective antagonists prazosin (1 microM) and terazosin (1 microM) both blocked contractions to phenylephrine (10 microM). The L-type calcium channel blocker nifedipine (10 microM), and the PKC inhibitors Gö 6976 (1 microM) and bisindolylmaleimide (1 microM) also inhibited phenylephrine-induced contractions. 3 Phenylephrine caused a concentration dependent increase in inositol phosphate production (EC(50) 119+/-67 nM). This response was blocked by terazosin (1 microM). 4 Phenylephrine caused the translocation of the PKC alpha isoform, but not the beta, delta, gamma, epsilon or lambda isoforms, from the cytosolic to the particulate fraction of HCPSC, with an EC(50) of 5.7+/-0.5 microM. 5 In FURA-2AM (5 microM) loaded cells, phenylephrine elicited concentration dependent increases in [Ca(2+)](i), with an EC(50) of 3.9+/-0.4 microM. The response to phenylephrine (10 microM) was blocked by prazosin (1 microM), bisindolymaleimide (1 microM), and nifedipine (10 microM). 6 In conclusion, this study has shown that HCPSC express functional alpha(1)-adrenoceptors, and that the intracellular pathways responsible for contractility may be largely dependent upon protein kinase C activation and subsequent opening of L-type calcium channels.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2003

A meta-analysis review of the effects of recombinant bovine somatotropin. 1. Methodology and effects on production.

This manuscript presents the results of a review of the effects of recombinant bovine somatotropin (rBST) on milk production, milk composition, dry matter intake, and body condition score that was carried out by an expert panel established by the Canadian Veterinary Medical Association (CVMA). The panel was established by the CVMA in response to a request from Health Canada in 1998 and their report was made public in 1999. A series of meta-analyses was used to combine data on production and nutrition related parameters that were extracted from all randomized clinical trials, which had been published in peer-reviewed journals or which were provided by Health Canada, from the submission by Monsanto for registration of rBST in Canada. A companion paper will present the results of the effects of the drug on measures of health, reproductive performance, and culling parameters. Recombinant bovine somatotropin was found to increase milk production by 11.3% in primiparous cows and 15.6% in multiparous cows; although there was considerable variation from study to study. While some statistically significant effects on milk composition (% butterfat, protein, and lactose) were found, they were all very small. Treatment increased dry matter intake by an average 1.5 kg/day during the treatment period and dry matter intake remained elevated on into the first 60 days of the subsequent lactation. Despite the increase in dry matter intake, treated animals had lower body condition scores at the end of the treatment period, and the reduced scores persisted through until the start of the subsequent lactation.

Animals↗
PubMed2003

A meta-analysis review of the effects of recombinant bovine somatotropin. 2. Effects on animal health, reproductive performance, and culling.

This manuscript presents the results of a review of the effects of recombinant bovine somatotropin (rBST) on dairy cattle health, reproductive performance, and culling, that was carried out by an expert panel established by the Canadian Veterinary Medical Association (CVMA). The panel was established by the CVMA in response to a request from Health Canada in 1998 and their report was made public in 1999. A series of meta-analyses was used to combine data on health-related parameters that were extracted from all randomized clinical trials that had been published in peer-reviewed journals or which were provided by Health Canada from the submission by Monsanto for registration of rBST in Canada. A companion paper (1) presents the estimates of the effect of the drug on production parameters. Recombinant bovine somatotropin was found to increase the risk of clinical mastitis by approximately 25% during the treatment period but there was insufficient data to draw firm conclusions about the effects of the drug on the prevalence of subclinical intra-mammary infections. Use of rBST increased the risk of a cow failing to conceive by approximately 40%. For cows which did conceive, there was no effect on services per conception and only a small increase in average days open (5 days). Use of the drug had no effect on gestation length, but the information about a possible effect on the risk of twinning was equivocal. Cows treated with rBST had an estimated 55% increase in the risk of developing clinical signs of lameness. Few studies reported data on culling, but based on those that did, there appeared to be an increase risk of culling evident in multiparous cows. Use of the drug in 1 lactation period appeared to reduce the risk of metabolic diseases (particularly ketosis) in the early period of the subsequent lactation.

Animals↗
PubMed2001

Influences on the implementation of TQM in health care organizations: professional bureaucracies, ownership and complexity.

TQM is introduced into many organisations in an attempt to improve productivity and quality. There are a number of organisational variables that have been recognised as influencing the success of TQM implementation including leadership, teamwork, and suppliers. This paper presents findings of a study of the implementation of TQM in Australian health care organisations. Structural factors were observed to affect the progress of TQM. Professional bureaucracies were less successful than machine bureaucracies. Private organisations were more successful than their public counterparts.

Australia↗
PubMed2001

New aspects of the role of MR/P fimbriae in Proteus mirabilis urinary tract infection.

Proteus mirabilis, a common cause of urinary tract infection (UTI), produces a number of different fimbriae including mannose-resistant Proteus-like fimbriae (MR/P). The precise role of different P. mirabilis fimbriae in ascending UTI has not yet been elucidated. In this study, a clinical isolate of P. mirabilis and an isogenic mutant unable to express MR/P were tested using different experimental approaches. They were tested for their ability to cause infection in an ascending co-infection model of UTI and in a haematogenous model in the mouse. In both models, the mutant was less able than the wild-type strain to colonise the lower and upper urinary tracts although infectivity was not abolished. In vitro adherence to uroepithelial cells was also assessed. Significant differences in adherence between both strains were observed at 1 h but not at 15 min post infection. We have also shown that a wild-type strain carries two copies of the mrpA gene. These data reinforce the importance of MR/P fimbriae in P. mirabilis UTI although other virulence factors may be necessary for efficient colonisation and development of infection.

Animals↗
PubMed2001

Over-the-counter advice for genital problems: the role of the community pharmacist.

This year, in the UK, levonorgestrel was approved for sale in pharmacies for emergency contraception. This study assessed, using a postal questionnaire, the ability of community pharmacists to provide advice relating to sexual health, their comfort and training in this area, and their knowledge of local genitourinary medicine (GUM) services. Fifty-four per cent of pharmacists responded. Most (79%) did not know where their nearest GUM department was; only 21% had ever advised a patient to attend a GUM clinic. Twenty-nine per cent said they were not able to broach the possibility of a sexually transmitted infection (STI) with a patient of both sexes. Forty-four per cent had received training related to post-coital contraception. Greater liaison between GUM departments and community pharmacists is suggested as a way of increasing the proportion of patients presenting to a pharmacist who are referred appropriately to a GUM clinic.

Attitude of Health Personnel↗
PubMed2000

Effects of adenine nucleosides and nucleotides on neuromuscular transmission to the prostatic stroma of the rat.

1. The aim of this study was to investigate the effects of adenine nucleosides and nucleotides on contractility of the smooth muscle of rat prostate gland. 2. Nerve terminals within rat isolated prostatic tissues were electrically field stimulated (60 V, 0.5 ms, 10 Hz, 20 pulses every 60 s). Adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP) and adenosine had no effect on baseline smooth muscle tone but concentration-dependently inhibited electrically-evoked contractile responses. The relative order of potency was ATP congruent with AMP congruent with adenosine>ADP. 3. The inhibition by ATP and adenosine of field stimulation-induced contractions in the rat prostate was antagonized by 8-phenyltheophylline (10 microM), but not by suramin (100 microM) and only slightly by reactive blue 2 (5 microM). 4. The adenosine metabolizing enzyme adenosine deaminase (0.1 unit ml(-1)) inhibited the inhibitory effects of ATP and adenosine. The P2 purinoceptor agonist 2-methylthio ATP (10 nM - 0.1 mM), had no effect on field stimulation-induced contractions of the rat prostate. 5. ATP and adenosine did not modify the contractile responses of the rat prostate to exogenously added noradrenaline (10 microM). 6. Inhibitory concentration-response curves to a number of adenosine analogues with differing stabilities and selectivities for the different adenosine receptors yielded a relative rank order of agonist potency of: N(6)-cyclopentyladenosine (CPA)>N(6)-cyclohexyladenosine (CHA) congruent with (-)-N(6)-(2-phenylisopropyl)-adenosine (R-PIA) congruent with 5'-(N-ethylcarboxamido)-adenosine (NECA)>(+)-N(6)-(2-phenylisopropyl)-adenosine (S-PIA)>2-p-[2-carboxyethyl]phenethyl-amino-5'-N-ethylcarboxamido-ade nosine (CGS 21680). 7. These results indicate that adenine nucleoside and nucleotide induced inhibition of electrically-evoked contractions in the rat prostate occurs through activation of adenosine but not ATP receptors. The relative order of potency of adenosine analogues is consistent with activation of receptors of the A(1)-adenosine receptor subtype. These receptors appear to be prejunctional.

Adenosine Diphosphate↗
PubMed2000

Non-typeable Haemophilus influenzae adhere to and invade human bronchial epithelial cells via an interaction of lipooligosaccharide with the PAF receptor.

Adherence and invasion are thought to be key events in the pathogenesis of non-typeable Haemophilus influenzae (NTHi). The role of NTHi lipooligosaccharide (LOS) in adherence was examined using an LOS-coated polystyrene bead adherence assay. Beads coated with NTHi 2019 LOS adhered significantly more to 16HBE14 human bronchial epithelial cells than beads coated with truncated LOS isolated from an NTHi 2019 pgmB:ermr mutant (P = 0.037). Adherence was inhibited by preincubation of cell monolayers with NTHi 2019 LOS (P = 0.0009), but not by preincubation with NTHi 2019 pgmB:ermr LOS. Competitive inhibition studies with a panel of compounds containing structures found within NTHi LOS suggested that a phosphorylcholine (ChoP) moiety was involved in adherence. Further experiments revealed that mutations affecting the oligosaccharide region of LOS or the incorporation of ChoP therein caused significant decreases in the adherence to and invasion of bronchial cells by NTHi 2019 (P < 0.01). Analysis of infected monolayers by confocal microscopy showed that ChoP+ NTHi bacilli co-localized with the PAF receptor. Pretreatment of bronchial cells with a PAF receptor antagonist inhibited invasion by NTHi 2109 and two other NTHi strains expressing ChoP+ LOS glycoforms exhibiting high reactivity with an anti-ChoP antibody on colony immunoblots. These data suggest that a particular subset of ChoP+ LOS glycoforms could mediate NTHi invasion of bronchial cells by means of interaction with the PAF receptor.

Bacterial Adhesion↗
PubMed2000

Multiple roles for Bordetella lipopolysaccharide molecules during respiratory tract infection.

Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica are closely related subspecies that cause respiratory tract infections in humans and other mammals and express many similar virulence factors. Their lipopolysaccharide (LPS) molecules differ, containing either a complex trisaccharide (B. pertussis), a trisaccharide plus an O-antigen-like repeat (B. bronchiseptica), or an altered trisaccharide plus an O-antigen-like repeat (B. parapertussis). Deletion of the wlb locus results in the loss of membrane-distal polysaccharide domains in the three subspecies of bordetellae, leaving LPS molecules consisting of lipid A and core oligosaccharide. We have used wlb deletion (Deltawlb) mutants to investigate the roles of distal LPS structures in respiratory tract infection by bordetellae. Each mutant was defective compared to its parent strain in colonization of the respiratory tracts of BALB/c mice, but the location in the respiratory tract and the time point at which defects were observed differed significantly. Although the Deltawlb mutants were much more sensitive to complement-mediated killing in vitro, they displayed similar defects in respiratory tract colonization in C5(-/-) mice compared with wild-type (wt) mice, indicating that increased sensitivity to complement-mediated lysis is not sufficient to explain the in vivo defects. B. pertussis and B. parapertussis Deltawlb mutants were also defective compared to wt strains in colonization of SCID-beige mice, indicating that the defects were not limited to interactions with adaptive immunity. Interestingly, the B. bronchiseptica Deltawlb strain was defective, compared to the wt strain, in colonization of the respiratory tracts of BALB/c mice beginning 1 week postinoculation but did not differ from the wt strain in its ability to colonize the respiratory tracts of B-cell- and T-cell-deficient mice, suggesting that wlb-dependent LPS modifications in B. bronchiseptica modulate interactions with adaptive immunity. These data show that biosynthesis of a full-length LPS molecule by these three bordetellae is essential for the expression of full virulence for mice. In addition, the data indicate that the different distal structures modifying the LPS molecules on these three closely related subspecies serve different purposes in respiratory tract infection, highlighting the diversity of functions attributable to LPS of gram-negative bacteria.

Animals↗
PubMed1999

Predicting 'normal' grip strength for rheumatoid arthritis patients.

OBJECTIVE: An ability to predict accurately 'normal' grip strength in rheumatoid arthritis (RA) patients would facilitate a more accurate assessment of the degree of their functional loss. This, in turn, would allow the setting of more meaningful treatment goals aimed at restoring hand function towards normal. This study carefully measures three modalities of hand grip strength and their correlation with multiple simple anthropometric parameters in normal subjects. We aim to determine which of these parameters are best correlated to grip strength, and whether this correlation is strong enough to allow the accurate prediction of what normal grip strength should be in RA patients. METHODS: In 81 normal subjects (67 female), power, pinch and tripod grip strength measurements were made using an MIE digital pinch grip analyser. These strength data were correlated with specific local forearm anthropometric measurements: forearm circumference, forearm length, forearm volume, hand circumference, hand length, hand volume, hand and forearm volume, and various general anthropometric parameters (weight, height and age). These normal subjects had been chosen so as to be age and sex matched with 83 RA patients (67 female) in whom the same strength and anthropometric parameters were assessed and correlated. In patients, the grip strength results were additionally correlated with two markers of disease activity: a modified Ritchie Articular Index local to the hand and forearm (mRAI) and a visual analogue scale (VAS) assessing subjective pain severity. RESULTS: In normal subjects, clear correlations were demonstrated between hand grip strengths and all specific anthropometric variables, the strongest correlation being with forearm and hand volume (r = 0.729 and 0.638 for dominant and non-dominant hands, respectively; P < 0.01 for both). The patients were considerably weaker than normal subjects. Markers of disease activity showed a negative correlation with grip strength. In normal subjects, the dominant hand was significantly stronger than the non-dominant hand, and on average by 8%, while the opposite was true in patients, who were 20% weaker on the dominant side. CONCLUSION: Simple anthropometric measurements, and forearm and hand volume in particular, would be useful at baseline for predicting 'normal' hand grip strength in RA patients, both in the clinical setting and in research trials aimed at improving grip strength and hand function.

Aged↗
PubMed1999

Genetic basis for lipopolysaccharide O-antigen biosynthesis in bordetellae.

Bordetella bronchiseptica and Bordetella parapertussis express a surface polysaccharide, attached to a lipopolysaccharide, which has been called O antigen. This structure is absent from Bordetella pertussis. We report the identification of a large genetic locus in B. bronchiseptica and B. parapertussis that is required for O-antigen biosynthesis. The locus is replaced by an insertion sequence in B. pertussis, explaining the lack of O-antigen biosynthesis in this species. The DNA sequence of the B. bronchiseptica locus has been determined and the presence of 21 open reading frames has been revealed. We have ascribed putative functions to many of these open reading frames based on database searches. Mutations in the locus in B. bronchiseptica and B. parapertussis prevent O-antigen biosynthesis and provide tools for the study of the role of O antigen in infections caused by these bacteria.

Bordetella↗
PubMed1999

Screening for urinary tract infections in a gynaecological setting: validity and cost-effectiveness of reagent strips.

This study aims to test the validity and cost-effectiveness of reagent-strip analysis compared with microbiological laboratory testing for mass screening of urine for urinary tract infections in a gynaecological setting. Over a six-month period, urine samples from a convenient group of 228 women presenting in a gynaecological ward of an NHS Trust hospital were tested using Ames 8SG reagent strips to detect leucocyte esterase and nitrite. Total bacterial counts were also carried out; urine culture was recorded as positive if there was > 10(5) organisms/mL. Validity of the dipstick tests was measured, using four criteria (sensitivity, specificity, positive predictive value [PPV] and negative predictive value [NPV]), against the results of laboratory analysis. The combined use of the leucocyte esterase and nitrite tests produced results as follows: sensitivity, 96.4%; specificity, 88.5%; PPV, 54%; and NPV, 99.4%. Cost-effectiveness for visible costs was calculated as 48.6% for the 12.3% rate of infection in this study. The use of reagent strips in a mass-screening programme in a gynaecological setting proved both valid and cost-effective.

Cost-Benefit Analysis↗
PubMed1997

Ultrastructural analysis of primary human urethral epithelial cell cultures infected with Neisseria gonorrhoeae.

In men with gonococcal urethritis, the urethral epithelial cell is a site of infection. To study the pathogenesis of gonorrhea in this cell type, we have developed a method to culture primary human urethral epithelial cells obtained at the time of urologic surgery. Fluorescent analysis demonstrated that 100% of the cells stained for keratin. Microscopic analyses indicated that these epithelial cells arrayed in a pattern similar to that seen in urethral epithelium. Using immunoelectron and confocal microscopy, we compared the infection process seen in primary cells with events occurring during natural infection of the same cell type in men with gonococcal urethritis. Immunoelectron microscopy studies of cells infected with Neisseria gonorrhoeae 1291 Opa+ P+ showed adherence of organisms to the epithelial cell membrane, pedestal formation with evidence of intimate association between the gonococcal and the epithelial cell membranes, and intracellular gonococci present in vacuoles. Confocal studies of primary urethral epithelial cells showed actin polymerization upon infection. Polyclonal antibodies to the asialoglycoprotein receptor (ASGP-R) demonstrated the presence of this receptor on infected cells in the primary urethral cell culture. In situ hybridization using a fluorescent-labeled probe specific to the ASGP-R mRNA demonstrated this message in uninfected and infected cells. These features were identical to those seen in urethral epithelial cells in exudates from males with gonorrhea. Infection of primary urethral cells in culture mimics events seen in natural infection and will allow detailed molecular analysis of gonococcal pathogenesis in a human epithelial cell which is commonly infected.

Asialoglycoprotein Receptor↗
PubMed1997

A comparison of three electrodes for the measurement of pH in small volumes.

An ion-sensitive field effect transistor (ISFET, Sentron, Sentron, Inc.) electrode was compared with a glass combination micro-electrode (MI-410, Micro-electrodes, Inc.) and a solid-state metal wire oxide pH sensor (Beetrode, World Precision Instruments, Inc.) with a liquid junction reference electrode (MERE1, World Precision Instruments, Inc.). The electrodes were assessed for linearity, reproducibility, accuracy, drift from the initial calibration between pH 4 and pH 7 and the time taken to record a stable reading. The ISFET was used to determine the pH in dental plaque samples (1 mg suspended in 20 microliters). The pH values correlated with the hydrogen ion concentration for all the electrodes (r = 0.98). The MI-410 fractured before this evaluation was completed. Coefficients of variation were 0.65% (pH 4) and 0.08% (pH 7) for the ISFET and 4.69% (pH 4) and 3.46% (pH 7) for the Beetrode. Both electrodes gave readings that differed significantly from the initial calibration, but the drift was greater for the Beetrode (F = 7.93; p = 0.0005) than the ISFET (F = 1.89; p = 0.1519). However, this drift was smaller than the change in pH as measured in dental plaque samples. The Beetrode gave a stable reading after 3.39 +/- 0.83 s and the ISFET after 2.2 +/- 0.76 s, while the MI-410 required at least 20 s. The ISFET type electrode is suitable for use in small volumes such as plaque suspensions, is easier to operate and yields results closer to the initial calibration than the Beetrode and is more robust than the MI-410 and the Beetrode.

Analysis of Variance↗