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Biomedical subjects

C J Jackson

Publications and source records attributed to C J Jackson.

At least 19 recordsLinked to original sources

Referral and attendance at a specialist antenatal clinic: qualitative study of women's views.

OBJECTIVE: To explore women's views on being referred to and attending a specialist antenatal hypertension clinic. DESIGN: Qualitative interview study. SETTING: A pregnancy hypertension clinic in a large teaching hospital in the East Midlands. POPULATION: Twenty-one women (aged 18 years and above) attending the pregnancy hypertension clinic for the first time during their current pregnancy. METHODS: Women who had been referred to and attended a specialist antenatal clinic participated in semi-structured interviews. Data analysis was based on the constant comparative method. MAIN OUTCOME MEASURES: Women's experiences and perceptions of being referred to and attending a specialist antenatal clinic. RESULTS: Being referred to the clinic conferred an 'at risk' status on women. Some women welcomed the referral but others experienced it as unsettling. Many were unclear about why they had been identified as being at risk or had difficulties in accepting the legitimacy of the reason for referral. Women were often inadequately informed about why they were referred to the clinic, what they could expect and the benefits of attending the clinic over management in the community. Although attendance at the clinic was cited as a source of reassurance, the reassurance was often made necessary by concern raised by the initial referral. CONCLUSIONS: Women's accounts suggest that the interface between community and secondary antenatal services needs improvement to minimise possible adverse effects from identifying women as being 'at risk' during pregnancy.

Adolescent↗

Participating in a trial in a critical situation: a qualitative study in pregnancy.

BACKGROUND: Randomised controlled trials of interventions in critical situations are necessary to establish safety and evaluate outcomes. Pregnant women have been identified as a potentially vulnerable population. OBJECTIVE: To explore women's experiences of being recruited to ORACLE, a randomised controlled trial of antibiotics in pre-term labour. METHODS: Twenty qualitative interviews were conducted with women who had participated in ORACLE. Analysis was based on the constant comparative method. RESULTS: Women gave prominence to the socioemotional aspects of their interactions with healthcare professionals in making decisions on trial participation. Comments on the quality of written and spoken information were generally favourable, but women's accounts suggest that the stressful nature of the situation affected their ability to absorb the information. Women generally had poor understanding of trial design and practices. The main motivation for trial participation was the possibility of an improved outcome for the baby. The second and less prominent motivation was the opportunity to help others, but this was conditional on there being no risks associated with trial participation. In judging the risks of participation, women seemed to draw on "common sense" understandings including a perception that antibiotics were risk free. DISCUSSION: Recruitment to trials in critical situations raises important questions. Future studies should explore how rigorous governance arrangements for trials, particularly in critical situations, can protect participants rather than relying on ideals of informed consent that may be impossible to achieve. Future research should include a focus on interactions between research candidates and professionals involved in recruitment.

Antibiotic Prophylaxis↗

Interaction of cocultured decidual endothelial cells and cytotrophoblasts in preeclampsia.

Disturbed cell-cell communication between trophoblasts and the maternal endothelium may be responsible for the deficient endovascular invasion seen in preeclampsia. In vitro studies have been hampered by lack of suitable models to directly examine interactions between these cell types. Using a bilayer coculture model, we examined the effect of decidual endothelial cells on matrix metalloproteinase secretion and the migration of cytotrophoblasts from preeclamptic pregnancies. Cells were incubated on semipermeable membranes in 20% or 2% O(2) with or without the tumor promoter phorbol 12-myristate 13-acetate, which activates matrix metalloproteinase-2 and -9 in endothelial cells. Cytotrophoblasts from preeclamptic pregnancies secreted significantly less matrix metalloproteinase-2 and -9 than their normal counterparts. Although decidual endothelial cells downregulated cytotrophoblast migration in normal pregnancy, this was not observed in cocultures with cytotrophoblasts from preeclamptic pregnancies. In addition, cytotrophoblasts from preeclamptic pregnancies altered phorbol myristate acetate-induced activation of endothelial matrix metalloproteinases. Hypoxia increased cytotrophoblast migration when cells were incubated alone but not in coculture with decidual endothelial cells due to increased adhesion between the two cell types. These results suggest dysfunctional interactive regulation of migration and matrix metalloproteinase secretion in preeclampsia that could result in abnormal endovascular trophoblast invasion of the maternal vasculature.

Cell Communication↗

A synthesis of dominant ecological processes in intensive shrimp ponds and adjacent coastal environments in NE Australia.

One of the key environmental concerns about shrimp farming is the discharge of waters with high levels of nutrients and suspended solids into adjacent waterways. In this paper we synthesize the results of our multidisciplinary research linking ecological processes in intensive shrimp ponds with their downstream impacts in tidal, mangrove-lined creeks. The incorporation of process measurements and bioindicators, in addition to water quality measurements, improved our understanding of the effect of shrimp farm discharges on the ecological health of the receiving water bodies. Changes in water quality parameters were an oversimplification of the ecological effects of water discharges, and use of key measures including primary production rates, phytoplankton responses to nutrients, community shifts in zooplankton and delta15N ratios in marine plants have the potential to provide more integrated and robust measures. Ultimately, reduction in nutrient discharges is most likely to ensure the future sustainability of the industry.

Animals↗

Molecular strain typing of Trichophyton rubrum indicates multiple strain involvement in onychomycosis.

BACKGROUND: Trichophyton rubrum is an important cause of onychomycosis. Molecular strain typing methods have recently been developed to address questions of epidemiology and source of relapse following treatment. OBJECTIVES: To determine whether T. rubrum nail infections are caused by one or more strains of this fungus. METHODS: Nail specimens from 10 patients with onychomycosis due to T. rubrum were cultured and five colonies per culture plate were selected for molecular strain typing. DNA was extracted from these isolates and subjected to a polymerase chain reaction-based typing method that analyses variations in numbers of repetitive elements in the non-transcribed spacer region of the ribosomal RNA gene repeats. RESULTS: In six of 10 specimens, there were two or more T. rubrum strain types present. CONCLUSIONS: This preliminary study suggests that in many cases of fungal nail infection by T. rubrum, multiple strains are involved. This has important implications for epidemiological studies and possibly for therapy.

Adult↗

In vitro migration of cytotrophoblasts through a decidual endothelial cell monolayer: the role of matrix metalloproteinases.

Deficient trophoblast invasion is a major feature of pre-eclampsia. In vitro studies suggest that in normal pregnancy, maternal cells may play a role in controlling trophoblast invasion, although the exact nature of the regulatory interactions between these cells is not fully understood. To examine the effect of maternal-placental cell interactions on matrix metalloproteinase (MMP) secretion and endovascular cytotrophoblast migration in normal pregnancy and in pre-eclampsia, we performed co-culture experiments using cytotrophoblasts from normal pregnancies, together with decidual endothelial cells from both normal and preeclamptic pregnancies. Cells were incubated on semi-permeable membranes with or without phorbol 12-myristate 13-acetate (PMA). Results showed that third trimester cytotrophoblasts are migratory under basal conditions and display a different MMP profile from decidual endothelial cells. Co-culture did not damage either cell type and resulted in reduced latent MMP-9 secretion and reduced cytotrophoblast migration. Although PMA upregulated MMPs in decidual endothelial cells, it had no effect on cytotrophoblast MMP secretion. PMA, however, reduced cytotrophoblast migration. Pre-eclamptic decidual endothelial cells showed reduced MMP-1 secretion, but overall were not different in co-culture from normal endothelial cells. This study demonstrates the effectiveness of a bilayer co-culture model to study maternal-foetal cell interactions and provides evidence that maternal cells may contribute to the control of endovascular cytotrophoblast invasion.

Adult↗

Analysis of 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane in rat plasma. II. Pharmacokinetic profile in male and female Sprague-Dawley rats evaluated by capillary electrophoresis.

This paper describes a pharmacokinetic study performed in Sprague-Dawley rats after i.v. administration of a single 6-mg/kg dose of 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane (Altropane). Plasma samples were collected from the retro-orbital sinus at times up to 3 h after drug administration, extracted by solid-phase extraction, and the drug levels determined by capillary electrophoresis (CE). Pharmacokinetic parameters were determined by a standard noncompartmental model using WinNonlin version 1.5. The maximum plasma concentrations, clearances of the drug, and areas under the curve for male and female rats were 5.74 and 7.26 microg/ml, 135.7 and 98.5 ml/kg x min, and 44.23 and 60.92 microg x min/ml, respectively. The drug was cleared very rapidly from the systemic circulation, with a terminal t(1/2) of 7 to 10 min and a mean residence time of about 11 min for both sexes. The volume of distribution was approximately 1 l/kg. No metabolites were detected when the samples were analyzed individually. However, after samples were pooled and concentrated, traces of two unknown peaks that may represent metabolites were detected in concentrates from the last two timepoints. Part I of this work [J. Chromatogr. A, 895 (2000) 87] describes validation of CE methods for the analysis of aqueous and plasma samples of Altropane, including its solid-phase extraction from rat plasma.

Animals↗

Human endothelial gelatinases and angiogenesis.

Endothelial cell invasion is an essential event during angiogenesis (formation of new blood vessels). The process involves the degradation of the basement membrane and the underlying interstitium. The matrix metalloproteinase (MMP) family is considered to be primarily responsible for matrix degradation. Two members of the family, gelatinase A and B play an important role in angiogenesis. This review outlines recent findings on their regulation in human endothelial cells. Latent gelatinase B is secreted from endothelial cells. This enzyme can also accumulate in the cytosol as an active enzyme, free of TIMP-1. In contrast, latent gelatinase A is constitutively secreted from the cells. Unlike other MMPs, gelatinase A activation occurs on the cell membrane and is mediated by MT1-MMP. A number of physiological activators have recently been described. These include thrombin and activated protein C, both of which activate gelatinase A independent of the MT1-MMP pathway. These new findings may lead to therapeutic interventions for the treatment of angiogenic-dependent diseases such as cancer and arthritis.

Cell Membrane↗

An old activity in the cytochrome P450 superfamily (CYP51) and a new story of drugs and resistance.

Cytochrome P450 51 (CYP51) is sterol 14alpha-demethylase, known also as Erg11p in yeast. First studied in yeast, where it is one of three CYPs in the genome, it has subsequently gained attention as the only CYP found so far in different kingdoms of life. As such it is central to considerations of CYP evolution. Recent use of CYP51-inhibiting antifungal drugs, such as fluconazole, has also been associated with dramatic CYP51 evolution to numerous resistant forms in fungal pathogens. CYP51 has also been discovered in mycobacteria where antifungal azoles have effect and might be of value against tuberculosis. Evolutionary and therapeutic aspects of CYP51 studies are discussed.

Amino Acid Sequence↗

Moderating effect of ear preference on personality in the prediction of sales performance.

This study examined the relationship between ear preference, personality, and performance ratings on 203 telesales staff. Social desirability scores were a significant predictor of two relatively independent sets of supervisor ratings (actual performance and developmental potential) in interaction with ear preference. It was found that the social desirability scale was a significant positive predictor for staff preferring a right ear headset, but a negative predictor for staff preferring a left ear headset. These results were interpreted in terms of different strategies used to achieve successful sales.

Journal Article↗

Molecular identification and strain typing of dermatophyte fungi.

The rDNA spacer regions provide easily accessible, polymorphic genetic loci for both species and strain identification of dermatophyte fungi. Nucleotide substitutions and length polymorphisms in the internal transcribed spacers (ITS) can be indexed by sequencing or by PCR restriction endonuclease analysis, and provide a rapid and accurate means of identifying dermatophyte taxa. Multiple sets of tandem repeats that vary in copy number both within and between strains produce length heterogeneity in the nontranscribed spacer (NTS) region. Amplification of these repeats using specific PCR, or their detection by Southern hybridisation with a generic ribosomal DNA probe, provides a sensitive and discriminatory technique for strain identification in T. rubrum and other dermatophyte fungi.

Arthrodermataceae↗

Bactericidal and inhibitory effects of azole antifungal compounds on Mycobacterium smegmatis.

Azole antifungals are central to therapy and act by inhibiting a cytochrome P450, sterol 14-demethylase and blocking normal sterol synthesis. Our recent identification of a mycobacterial sterol biosynthetic pathway led us to probe the efficacy of a range of these compounds against Mycobacterium smegmatis. Several showed equivalent or greater inhibitory effects to those against Candida albicans, and bactericidal activity was demonstrated for four compounds, clotrimazole, econazole, miconazole and tebuconazole. The major drug used clinically, fluconazole, was ineffective. The results are discussed in the light of the world-wide spread of tuberculosis, including drug-resistant forms and the requirement for new drugs.

Antifungal Agents↗

Activated protein C directly activates human endothelial gelatinase A.

Angiogenesis (formation of new blood vessels) occurs in a number of diseases such as cancer and arthritis. The matrix metalloproteinase (MMP), gelatinase A, is secreted by endothelial cells and plays a vital role during angiogenesis. It is secreted as a latent enzyme and requires extracellular activation. We investigated whether activated protein C (APC), a pivotal molecule involved in the body's natural anti-coagulant system, could activate latent gelatinase A secreted by human umbilical vein endothelial cells (HUVEC). APC induced the fully active form of gelatinase A in a dose (100-300 nM)- and time (4-24 h)-responsive manner. The inactive zymogen, protein C, did not activate gelatinase A when used at similar concentrations. APC did not up-regulate membrane type 1 MMP (MT1-MMP) mRNA in HUVEC. In addition, the MMP inhibitor, 1, 10-phenanthroline (10 nM), was unable to inhibit APC-induced activation. These results suggested that MT1-MMP was not involved in the activation process. APC activation of gelatinase A occurred in the absence of cells, indicating that it acts directly. APC may contribute to the physiological/pathological mechanism of gelatinase A activation, especially during angiogenesis.

Cells, Cultured↗

Effect of soy protein foods on low-density lipoprotein oxidation and ex vivo sex hormone receptor activity--a controlled crossover trial.

Plant-derived estrogen analogs (phytoestrogens) may confer significant health advantages including cholesterol reduction, antioxidant activity, and possibly a reduced cancer risk. However, the concern has also been raised that phytoestrogens may be endocrine disrupters and major health hazards. We therefore assessed the effects of soy foods as a rich source of isoflavonoid phytoestrogens on LDL oxidation and sex hormone receptor activity. Thirty-one hyperlipidemic subjects underwent two 1-month low-fat metabolic diets in a randomized crossover study. The major differences between the test and control diets were an increase in soy protein foods (33 g/d soy protein) providing 86 mg isoflavones/2,000 kcal/d and a doubling of the soluble fiber intake. Fasting blood samples were obtained at the start and at weeks 2 and 4, with 24-hour urine collections at the end of each phase. Soy foods increased urinary isoflavone excretion on the test diet versus the control (3.8+/-0.7 v 0.0+/-0.0 mg/d, P < .001). The test diet decreased both oxidized LDL measured as conjugated dienes in the LDL fraction (56+/-3 v 63+/-3 micromol/L, P < .001) and the ratio of conjugated dienes to LDL cholesterol (15.0+/-1.0 v 15.7+/-0.9, P = .032), even in subjects already using vitamin E supplements (400 to 800 mg/d). No significant difference was detected in ex vivo sex hormone activity between urine samples from the test and control periods. In conclusion, consumption of high-isoflavone foods was associated with reduced levels of circulating oxidized LDL even in subjects taking vitamin E, with no evidence of increased urinary estrogenic activity. Soy consumption may reduce cardiovascular disease risk without increasing the risk for hormone-dependent cancers.

Adult↗

Three-dimensional collagen matrices induce delayed but sustained activation of gelatinase A in human endothelial cells via MT1-MMP.

Gelatinase A, a member of the matrix metalloproteinase (MMP) family, plays an important role during angiogenesis. It is constitutively expressed by human endothelial cells as a latent enzyme and requires activation. Thrombin is the only described physiological inducer of gelatinase A in human endothelial cells. In this study, we investigated the mechanisms of gelatinase A activation by another physiological inducer, collagen. Endothelial cells were cultured on various ECM components for 24 h and the conditioned media were assessed for gelatinase A activity using gelatin zymography. The results demonstrated that type I collagen matrix specifically activates gelatinase A after 24 h in human umbilical vein and 48 h in neonatal foreskin endothelial cells. In contrast, thrombin activated gelatinase A after only 2 h. Activation by collagen was sustained over long periods of time in culture (96 h). Unlike thrombin-induced activation, collagen required active membrane type 1-MMP (MT1-MMP) on the endothelial cell surface to activate gelatinase A. In addition, collagen-induced activation of gelatinase A was inhibited by antibodies to the integrin receptor, alpha(2)beta(1), but not alpha(3)beta(1). Our findings, that collagen can provide long-term activation of gelatinase A are likely to be relevant to endothelial cell invasion during angiogenesis.

Cells, Cultured↗

Effect of soy-based breakfast cereal on blood lipids and oxidized low-density lipoprotein.

Consumption of soy protein may reduce the risk of cardiovascular disease both through reduction in serum lipids and by the antioxidant properties of protein-associated soy isoflavones. However, the effect that processing required for the manufacture of breakfast cereals may have on the lipid lowering and antioxidant activities of soy has not been studied. We have therefore assessed the health benefits of soy incorporation into breakfast cereals. Twenty-five hyperlipidemic men and women took soy (providing 36 g/d soy protein and 168 mg/d isoflavones) and control breakfast cereals, each for 3 weeks in a randomized crossover study with a 2-week washout period between treatments. Fasting blood samples were obtained pretreatment and at weeks 2 and 3 of each treatment. No significant difference was seen in serum lipids between treatments at week 3 apart from a 3.8% +/- 1.5% higher apolipoprotein A-1 level on control versus soy (P = .021). However, oxidized low-density lipoprotein (LDL) was reduced on the test compared with the control both as total dienes in LDL and as the ratio of conjugated dienes to cholesterol in the LDL fraction by 9.2% +/- 4.3% (P = .042) and 8.7% +/- 4.2% (P = .050), respectively. High isoflavone intakes in soy breakfast cereals may decrease the risk of cardiovascular disease by reducing oxidized LDL, while having no significant effect on the absolute concentration of LDL cholesterol.

Adult↗

Strain identification of Trichophyton rubrum by specific amplification of subrepeat elements in the ribosomal DNA nontranscribed spacer.

Trichophyton rubrum is the commonest cause of dermatophytosis of skin and nail tissue. Molecular characterization of the T. rubrum ribosomal DNA nontranscribed-spacer region revealed two novel tandemly repetitive subelements (TRSs): TRS-1, containing a 27-bp palindromic sequence, and TRS-2. Specific amplification of TRS-1 produced strain-characteristic banding patterns (PCR types), with 21 TRS-1 PCR types recognized from 101 clinical isolates. Four simple patterns representing 1 to 4 copies of TRS-1 accounted for 75 (75%) of all 101 strains, whereas more complex patterns were observed for 21 (20%) of the 101 isolates. The copy number of TRS-2 was 0 to 3 repeats per cistron, with a majority of isolates having two copies of this element. Eleven isolates were polymorphic for TRS-2, and in combination, 23 separate PCR types were recognized by amplification of both TRS-1 and TRS-2. The PCR patterns from both elements were stable and reproducible. Elements with homology to TRS-1 were present in three phylogenetically related species, Trichophyton violaceum, Trichophyton gourvilii, and Trichophyton soudanense, but these elements were not identified in other dermatophyte taxa. There was no clear correlation of PCR type with specimen (skin or nail tissue), but certain PCR types appeared to show a bias in geographic distribution. This new method of typing T. rubrum will enable important questions about pathogenesis and epidemiology of this fungus to be addressed.

Base Sequence↗

The structure of the Eysenck Personality Profiler.

The dominant issue in personality research over the last decade has been concerned with the fundamental structure of personality and the best measures of that structure. Exploratory factor analysis was used to investigate possible three- and five-factor solutions to the Eysenck Personality Profiler (EPP; Eysenck, Barrett, Wilson, & Jackson, 1992) which consists of 21 primary scales categorized under three super-factors. Little evidence was found to support Costa and McCrae's (1995) unequivocal comment that a five-factor solution fitted the data well. Confirmatory factor analysis was also used, by means of structural equation modelling, to estimate the goodness of fit of three- and five-factor models and little evidence was found to favour one solution over the other. A shorter version of the EPP, which consists of just nine scales, seemed to favour a three-factor solution. Various criticisms of the EPP are also made: some scales have relatively low alpha, there seem to be too many neuroticism scales and the three category response scales seem less than ideal.

Adult↗