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Biomedical subjects

E Davies

Publications and source records attributed to E Davies.

At least 37 records · Page 2Linked to original sources
PubMed2002

11beta-hydroxylase and aldosterone synthase expression in fetal rat hippocampal neurons.

The central nervous system produces many of the enzymes responsible for corticosteroid synthesis. A model system to study the regulation of this local system would be valuable. Previously, we have shown that primary cultures of hippocampal neurons isolated from the fetal rat can perform the biochemical reactions associated with the enzymes 11beta-hydroxylase and aldosterone synthase. Here, we demonstrate directly that these enzymes are present within primary cultures of fetal rat hippocampal neurons.

Adrenal Glands↗
PubMed2001

Medical evaluations in cases of suspected child sexual abuse: referrals and perceptions.

AIMS: To explore referrals to medical evaluations and children's and primary carers' experiences of those evaluations in Auckland. METHODS: Semi-structured interviews were conducted with children and young people who had made clear disclosures of sexual abuse, their primary carers and the social workers involved. RESULTS: More than 90% of children alleging penetration or attempted penetration were referred for a medical evaluation, but less than two thirds of children alleging oral genital or digital contact abuse were referred. Although the majority perceived the medical practitioners positively, many also commented on the distressing nature of the examinations, the photographs of children's genitalia and lack of preparation for those examinations. CONCLUSIONS: The findings highlight the need for improved preparation of children and their primary carers for medical evaluations. Ongoing discussion between referring agents and medical practitioners is desirable to ensure protocols are updated and adhered to.

Adolescent↗
PubMed2001

Effectiveness of Ginkgo biloba in treating tinnitus: double blind, placebo controlled trial.

OBJECTIVE: To determine whether Ginkgo biloba is effective in treating tinnitus. DESIGN: Double blind, placebo controlled trial using postal questionnaires. PARTICIPANTS: 1121 healthy people aged between 18 and 70 years with tinnitus that was comparatively stable; 978 participants were matched (489 pairs). INTERVENTION: 12 weeks' treatment with either 50 mg Ginkgo biloba extract LI 1370 three times daily or placebo. MAIN OUTCOME MEASURES: Participants' assessment of tinnitus before, during, and after treatment. Questionnaires included items assessing perception of how loud and how troublesome tinnitus was. Changes in loudness were rated on a six point scale. Changes in how troublesome were rated on a five point scale. RESULTS: There were no significant differences in primary or secondary outcome measures between the groups. 34 of 360 participants receiving active treatment reported that their tinnitus was less troublesome after 12 weeks of treatment compared with 35 of 360 participants who took placebo. CONCLUSIONS: 50 mg Ginkgo biloba extract LI 1370 given 3 times daily for 12 weeks is no more effective than placebo in treating tinnitus.

Adolescent↗
PubMed2001

Novel components of the plant cytoskeleton: a beginning to plant 'cytomics'

The bulk of our knowledge concerning the plant cytoskeleton has come primarily from the use of techniques and probes derived from animal research. However, in comparison with animal tissues, relatively few plant cytoskeleton proteins have been identified. We presume this is not because the plant cytoskeleton is really made up of such few proteins, but rather that only rarely have attempts been made to identify plant-specific cytoskeleton proteins, using plant-specific methods. Here we outline methods that we have developed both for the isolation and identification of novel cytoskeleton proteins as well as for the visualization of novel filamentous structures in plant cells, and we describe several novel cytoskeleton proteins and two novel cytoskeleton structures, 'nanofilaments' and 'nanotubules'. We postulate that use of such approaches will lead to a rapid expansion of our knowledge of the plant cytoskeleton.

Journal Article↗
PubMed2001

An influence of variation in the aldosterone synthase gene (CYP11B2) on corticosteroid responses to ACTH in normal human subjects.

OBJECTIVE: Previous evidence suggests that the efficiency of 11beta-hydroxylase is at least partly heritable and also that it may be mildly impaired in essential hypertension. In both cases, assessment of activity was based on the response of 11-deoxycorticosterone (DOC) and 11-deoxycortisol to ACTH. The gene (CYP11B1) coding for this enzyme is highly homologous with and lies a relatively short distance downstream from the gene coding for aldosterone synthase (CYP11B2) on chromosome 8. Two polymorphisms of CYP11B2 have been described. The first involves a change of -344C to T in a putative steroidogenic factor-1 (SF-1) binding site and the other, the intron conversion, an exchange of intron 2 for that of CYP11B1. These polymorphisms are in linkage dysequilibrium. Their effects on 11beta-hydroxylation were studied. METHODS AND RESULTS: Normal subjects (n = 135) were genotyped and those homozygous for either or both the polymorphisms were given ACTH (250 microg, i.v.). Plasma was sampled before and 30 minutes after administration. Basal concentrations of DOC, corticosterone, 11-deoxycortisol and cortisol and responses of corticosterone and cortisol to ACTH were not affected by genotype. However, the responses of DOC (P = 0.002 and P = 0.001, respectively) and 11-deoxycortisol (P = 0.025 and P = 0.002, respectively) were significantly greater in subjects homozygous for SF-1 T and/or intron conversion than in those homozygous for SF-1 C and/or normal intron. CONCLUSIONS: These results indicate different 11beta-hydroxylase efficiencies. Thus, variation in CYP11B2 appears to affect the product of CYP11B1. The mechanism is unclear. The close proximity of the two genes may lead to competition for transcription factors or specific differences in intron 2 may affect transcription. Alternatively, the polymorphisms may be acting as markers for adjacent functional genetic variations.

Adrenocorticotropic Hormone↗
PubMed2001

Polymorphic differences from normal in the aldosterone synthase gene (CYP11B2) in patients with primary hyperaldosteronism and adrenal tumour (Conn's syndrome).

OBJECTIVE: The hypertension of Conn's syndrome is due to autonomous aldosterone production by a unilateral adrenocortical adenoma. The source of tumour initiation and the reasons for excess aldosterone production as opposed to cortisol are not known, although variations in the promoter region of the gene coding for aldosterone synthase (CYP11B2) might account for the altered rate of aldosterone secretion. DESIGN: In a series (n = 27) of well-characterized Conn's syndrome cases, the aldosterone synthase gene (CYP11B2) was screened by single-strand conformational polymorphism (SSCP) for differences from the consensus sequence. RESULTS: No new mutations were found. The frequencies of two previously described linked polymorphisms, one a change of -344C to T in a putative steroidogenic factor-1 (SF-1) binding site and the other an exchange of intron 2 for that of CYP11B1 (conversion) were measured in tumour and genomic DNA. The frequency of the SF-1 T allele (P < 0.0001) and the conversion allele (P < 0.001) were markedly different between the Conn's syndrome group and the normal controls. However, the frequency did not differ between tumour and genomic DNA in the patient group. CONCLUSION: While it is unlikely that this difference from normal is related to tumour growth, these genotypes may predispose the tumour to aldosterone production.

Adenoma↗
PubMed2001

Disorders of mineralocorticoid synthesis.

Abnormalities of mineralocorticoid synthesis and/or metabolism profoundly affect the regulation of electrolyte and water balance and of blood pressure. Characteristic changes in extracellular potassium, sodium and hydrogen ion concentrations are usually diagnostic. Serious deficiency may be acquired, for example in Addison's disease, or inherited. In most of the inherited syndromes, the precise molecular changes in specific steroidogenic enzymes have been identified. Mineralocorticoid excess may be caused by aldosterone or 11-deoxycorticosterone by inadequate conversion of cortisol to cortisone by 11beta-hydroxysteroid dehydrogenase type 2 in target tissues (see Chapter 4), by glucocorticoid receptor deficiency or by constitutive activation of renal sodium channels. Changes in electrolyte balance and renin as well as the abnormal pattern of corticosteroid metabolism are usually diagnostic. Where these abnormalities are inherited (e.g. 11beta- or l7alpha-hydroxylase deficiencies, glucocorticoid remediable hyperaldosteronism (GRA), receptor defects, Liddle's syndrome), the molecular basis is again usually known and, in some cases, may provide the simplest diagnostic tests. Primary aldosteronism, although readily identifiable, presents problems of differential diagnosis, important because optimal treatment is different for each variant. Moreover, the mechanisms by which the variants develop are poorly understood. Finally, a significant proportion of patients with essential hypertension show characteristics of mild mineralocorticoid excess, for example low renin levels. Is this relevant to pathophysiology and, if so, is the effect induced via classic mechanisms of action or through newly discovered direct actions on the brain, heart and blood vessels? These questions are the subject of current research.

Adrenal Cortex Hormones↗
PubMed2001

Effects of 18-hydroxylated steroids on corticosteroid production by human aldosterone synthase and 11beta-hydroxylase.

In glucocorticoid-suppressible hyperaldosteronism, 11beta- hydroxylase activity is impaired. A chimeric enzyme formed from the control elements of 11beta-hydroxylase and the structural elements of aldosterone synthase is expressed ectopically in the zona fasciculata, thus exposing cortisol to aldosterone synthase. Increased quantities of 18-hydroxycortisol and 18-oxocortisol are synthesized, which, it has been suggested, might have a local inhibitory effect on the normal 11beta-hydroxylase. The effects of these compounds and also of 18-hydroxydeoxycorticosterone were tested in cells stably transfected with CYP11B1 and CYP11B2, the genes encoding 11beta-hydroxylase and aldosterone synthase, respectively. Neither 18-hydroxycortisol nor 18-oxocortisol affected the efficiency of use of 11-deoxycorticosterone or 11-deoxycortisol as substrates by the enzymes. 18-Hydroxydeoxycorticosterone significantly reduced the conversion rate of 11-deoxycorticosterone to corticosterone and that of 11-deoxycortisol to cortisol by both enzymes, but the production rate of 18- hydroxycorticosterone and aldosterone by aldosterone synthase increased. Aldosterone synthase was able to convert 18-hydroxydeoxycorticosterone to 18-hydroxycorticosterone and aldosterone, although its affinity for this substrate was lower (4.76 micromol/liter) than that for 11-deoxycorticosterone (0.11 micromol/liter). 11beta-Hydroxylase was unable to convert 18- hydroxydeoxycorticosterone to 18-hydroxycorticosterone. 18-Hydroxycortisol and 18-oxocortisol are not, therefore, the cause of lower 11beta-hydroxylase activity in glucocorticoid- suppressible hyperaldosteronism. 18-Hydroxydeoxycorticosterone can be converted to aldosterone, but its local concentration in man and its K(m) suggest that it is unlikely to be important.

Adrenal Cortex Hormones↗
PubMed2001

Presence of LH in gonadotropins associated with higher IVF pregnancy rates when basal serum LH is increased.

PURPOSE: To determine if pregnancy rates following in vitro fertilization-embryo transfer (IVF-ET) correlate with the presence or not of luteinizing hormone (LH) in the gonadotropins used for stimulation. Furthermore to see if the early follicular phase serum LH level affects pregnancy outcome according to the type of gonadotropins used. METHODS: The type of gonadotropins were prescribed randomly according to finances and convenience. Serum LH was obtained on day 2 or 3 of the menstrual cycle. RESULTS: When LH was > the median, significantly higher pregnancy rates were obtained in those treated with the follicle stimulating hormone (FSH)/human menopausal gonadotropin combination. When LH was < or = the median, significantly more oocytes were retrieved with FSH exclusively. No confounding variables were found to explain the data. CONCLUSIONS: Considering concerns of published studies that LH may have a toxic effect on pregnancy outcome, and if LH is suppressed too low, gonadotropins with exclusive FSH may not stimulate sufficient oocytes, the results were opposite to expectations.

Adult↗
PubMed2001

Transient dissociation of polyribosomes and concurrent recruitment of calreticulin and calmodulin transcripts in gravistimulated maize pulvini.

The dynamics of polyribosome abundance were studied in gravistimulated maize (Zea mays) stem pulvini. During the initial 15 min of gravistimulation, the amount of large polyribosomes transiently decreased. The transient decrease in polyribosome levels was accompanied by a transient decrease in polyribosome-associated mRNA. After 30 min of gravistimulation, the levels of polyribosomes and the amount of polyribosome-associated mRNA gradually increased over 24 h up to 3- to 4-fold of the initial value. Within 15 min of gravistimulation, total levels of transcripts coding for calreticulin and calmodulin were elevated 5-fold in maize pulvinus total RNA. Transcripts coding for calreticulin and calmodulin were recruited into polyribosomes within 15 min of gravistimulation. Over 4 h of gravistimulation, a gradual increase in the association of calreticulin and calmodulin transcripts with polyribosomes was seen predominantly in the lower one-half of the maize pulvinus; the association of transcripts for vacuolar invertase with polyribosomes did not change over this period. Our results suggest that within 15 min of gravistimulation, the translation of the majority of transcripts associated with polyribosomes decreased, resembling a general stress response. Recruitment of calreticulin and calmodulin transcripts into polyribosomes occurred predominantly in the lower pulvinus one-half during the first 4 h when the presentation time for gravistimulation in the maize pulvinus is not yet complete.

Biological Transport↗
PubMed2000

Molecular cloning and characterization of a tomato cDNA encoding a systemically wound-inducible bZIP DNA-binding protein.

Localized wounding of one leaf in intact tomato (Lycopersicon esculentum Mill.) plants triggers rapid systemic transcriptional responses that might be involved in defense. To better understand the mechanism(s) of intercellular signal transmission in wounded tomatoes, and to identify the array of genes systemically up-regulated by wounding, a subtractive cDNA library for wounded tomato leaves was constructed. A novel cDNA clone (designated LebZIP1) encoding a DNA-binding protein was isolated and identified. This clone appears to be encoded by a single gene, and belongs to the family of basic leucine zipper domain (bZIP) transcription factors shown to be up-regulated by cold and dark treatments. Analysis of the mRNA levels suggests that the transcript for LebZIP1 is both organ-specific and up-regulated by wounding. In wounded wild-type tomatoes, the LebZIP1 mRNA levels in distant tissue were maximally up-regulated within only 5 min following localized wounding. Exogenous abscisic acid (ABA) prevented the rapid wound-induced increase in LebZIP1 mRNA levels, while the basal levels of LebZIP1 transcripts were higher in the ABA mutants notabilis (not), sitiens (sit), and flacca (flc), and wound-induced increases were greater in the ABA-deficient mutants. Together, these results suggest that ABA acts to curtail the wound-induced synthesis of LebZIP1 mRNA.

Abscisic Acid↗
PubMed2000

Challenging the omnipotence of voices: group cognitive behavior therapy for voices.

The present study examines the impact of group based cognitive behavior therapy (CBT) for drug resistant auditory hallucinations, or voices. In particular it assesses treatment effect on beliefs in a voice's omnipotence and control. Twenty-two participants entered one of five 8-session CBT groups. Measures of omnipotence, control, process measures, and symptoms of anxiety and depression were completed at assessment, and first and last group sessions. The groups achieved a significant reduction in conviction in beliefs about omnipotence (df 2, P = 0.002) and control (df 2, P = 0.001). There were no affective changes. Certain participants showed important spontaneous changes in behavior. Process measures suggested that participants valued the groups and benefited from them. These results are promising and the treatment may prove a useful addition to existing psychological interventions.

Adult↗
PubMed2000

The MEK inhibitor, PD98059, reduces survival but does not block acute myeloid leukemia blast maturation in vitro.

The appearance of blasts in acute myeloid leukemia (AML) reflects a shift from cellular processes inducing maturation and cell death to those favouring survival and accumulation. We have monitored changes in the growth factor signalling molecule MAPKinase, in the cytoprotective protein Bcl-2 and in the cell death protein Bax, during maturation of proliferating and non-proliferating AML blasts in vitro. Eighteen AML samples were cultured for 7 d in serum-free medium with or without a supplement of recombinant cytokines comprising c-kit ligand, IL3 and GMCSF. Maturation of AML blasts, as assessed by morphology on Romanowsky-stained slides of 7/18 samples and by changes in surface CD markers on all 18 leukemias, occurred in both the absence and presence of cytokines. Cell numbers decreased to a mean of 71% after 7 d of cytokine-free culture, but increased to 210% in cytokine-supplemented cultures. The proportion of CD15-positive cells, assessed by flow cytometry, increased over 7 d in 17/18 samples, from a mean of 22% to 68% in cytokine-free cultures and to 72% in cytokine-supplemented cultures (p = < 0.0001 for both). By immunofluorescence/flow cytometry, there was no significant change in Bcl-2 over 7 d of culture, while Bax increased, particularly in cytokine-free cultures (2.2-fold), which led to a significant decrease in the Bcl-2/Bax ratio. Immunoblotting demonstrated that ERK was briefly phosphorylated after seeding AML blasts into culture. PD98059, an inhibitor of MAPKinase kinase (MEK) which activates MAPKinase, inhibited this transient ERK phosphorylation but was unable to block maturation as measured by acquisition of CD15 in samples from 12 patients with low starting numbers of CD15-positive cells. PD98059, however, reduced cell numbers in 7-d liquid culture and, in cytokine-supplemented cultures, this was associated with a 1.3-fold increase in Bcl-2 (p = 0.012) and a 1.4-fold increase in Bax (p = 0.02). Overall, these data demonstrate that most leukemic populations can partially differentiate in vitro without the need for cytokines or inducers. The MAPKinase pathway is not required for this maturation, but it does maintain cell viability in the absence or presence of cytokines. A rise in Bcl-2 may not protect AML blasts in the face of elevated Bax.

Acute Disease↗
PubMed2000

Capability of respirator wearers to detect aerosolized qualitative fit test agents (sweetener and Bitrex) with known fixed leaks.

This study was designed to evaluate and compare the ability of respirator wearers to detect qualitative respirator fit test agents (saccharin and Bitrex) when the respirators were modified to include fixed size leaks. In recent years the number of persons who require fit testing has increased, partly in response to the needs of health care workers with potential exposure to infectious bio-aerosols. Many health care providers have chosen qualitative respirator fit testing using saccharin and/or Bitrex for a variety of reasons, including (but not limited to) low initial equipment cost. Respirators were modified to include a mid-line sampling probe between the nose and mouth for quantitative fit testing with a TSI PortaCount. A second modification included the introduction of a shortened 14-gauge intravenous catheter at the bridge of the nose. The fixed leak was designed to produce fit factors < 100 when unplugged, with an average fit factor of 67 among 26 respirator wearers. A complete fit test was not performed, because one purpose of this study was to determine the ability of respirator wearers to detect a known fixed leak during a single normal breathing exercise, without introducing unknown and potentially variable size leaks. Sensitivity threshold screening included a placebo and requirement to correctly characterize the taste of the agent used. Quantitative fit factors without leaks ranged from 96 to > 20,000 and 22 to 160 with the leak present. Twenty four of 26 subjects had fit factors < 100 (92%) when fixed leaks were induced. All subjects correctly detected Bitrex with fixed leaks (sensitivity = 100%). Nine of 26 subjects (35%) were unable to detect saccharin in the presence of a known fixed leak even though the average fit factor for these subjects was 77. When the two subjects with fit factors > 100 were excluded, only 16 of 24 respirator wearers were able to detect saccharin with fixed leaks (sensitivity = 67%). There were several important aspects of our study design worth noting, including the introduction of a placebo during sensitivity threshold testing, limiting the subject response time to a single maneuver, using a higher concentration of Bitrex than commercially available, and requiring the subjects to correctly characterize the taste of the qualitative test agent. In conclusion, leak detection was correctly identified with Bitrex, but not saccharin.

Adolescent↗
PubMed2000

alpha-adducin and angiotensin I-converting enzyme polymorphisms in essential hypertension.

This study focused on two genes that have previously been implicated in hypertension and may influence renal sodium handling, adducin, and angiotensin I-converting enzyme (ACE). We compared their polymorphic frequencies and interaction in patients with essential hypertension (n=128) and individually age- and gender-matched normotensive control subjects. The alpha-adducin G460W polymorphism was genotyped by DNA amplification and restriction digestion. The ACE I/D polymorphism was assayed by a triple-primer method, with a "nested" polymerase chain reaction primer situated completely within the insertion sequence of the I: allele. The distributions of genotypes and alleles for the two polymorphisms were not significantly different between the case and control populations, and the cross-classification of cases by alpha-adducin and ACE genotype gave a distribution similar to that of control subjects. We have previously reported that the distributions of genotypes for two linked polymorphisms in the aldosterone synthase gene (one in the steroidogenic factor-1 [SF-1] binding site and the other an intronic conversion [IC]) were significantly different between this cohort of essential hypertensives and matched control subjects. The cross-classification of cases by alpha-adducin and SF-1, alpha-adducin and IC, ACE and SF-1, and ACE and IC genotype gave a distribution similar to that of control subjects. Hence, no evidence was found to suggest an association between either the alpha-adducin G460W or the ACE I/D polymorphism and hypertension in a careful case-control study. Furthermore, the alpha-adducin G460W, ACE I/D, and aldosterone synthase SF-1 and IC polymorphisms do not appear to interact in our hypertensive population.

Calmodulin-Binding Proteins↗