Search PubMed⌕ Search

Biomedical subjects

E Davies

Publications and source records attributed to E Davies.

At least 91 records · Page 5Linked to original sources

11 beta-Hydroxylase activity in glucocorticoid suppressible hyperaldosteronism: lessons for essential hypertension?

Corticosteroid 11 beta-hydroxylation is catalysed by 11 beta-hydroxylase and aldosterone synthase. Using plasma steroid ratios, the level of this process in patients with glucocorticoid-suppressible hyperaldosteronism (GSH) was compared with that in unaffected control subjects and in patients with Conn's syndrome. Based on both 11-deoxycortisol:cortisol (S:F) and 11-deoxycorticosterone:corticosterone (DOC:B) ratios, patients with GSH showed impaired resting 11 beta-hydroxylase activity. In GSH, but not in the other groups, the S:F ratio was significantly correlated with basal plasma aldosterone concentration. ACTH infusion increased the S:F ratio in all these patient groups, suggesting a common partial deficiency. The results also indicate that 11 beta-hydroxylation may be rate-limiting in normal subjects. In control subjects and patients with Conn's syndrome, the DOC:B ratio was not affected by ACTH. However, in GSH patients, this ratio fell markedly, indicating an increased efficiency of 11 beta-hydroxylation of DOC (but not S). This may be due to the activation by ACTH of the zona fasciculata chimaeric aldosterone synthase characteristic of this disease. Plasma aldosterone, corticosterone and DOC concentrations, appeared to be more sensitive to ACTH in GSH than the other groups. The defect in 11 beta-hydroxylation in GSH accounts for the increased levels of DOC reported in the condition, and may contribute to the phenotypic variability.

Adrenocorticotropic Hormone↗

Altered 11 beta-hydroxylase activity in glucocorticoid-suppressible hyperaldosteronism.

Corticosteroid 11 beta-hydroxylation is catalyzed by 11 beta-hydroxylase and aldosterone synthase. Using plasma steroid ratios, the level of this process in patients with glucocorticoid-suppressible hyperaldosteronism (GSH) was compared with that in unaffected control subjects and patients with Conn's syndrome. Based on both 11-deoxycortisol/cortisol (S:F) and 11-deoxycorticosterone/corticosterone (DOC:B) ratios, patients with GSH showed impaired resting 11 beta-hydroxylase activity. In GSH, but not in the other groups, the S:F ratio was significantly correlated with the basal plasma aldosterone concentration. ACTH infusion increased the S:F ratio in all of these patient groups, suggesting a common partial deficiency. The results also indicate that 11 beta-hydroxylation may be rate limiting in normal subjects. In control subjects and patients with Conn's syndrome, the DOC:B ratio was not affected by ACTH. However, in GSH patients, this ratio fell markedly, indicating an increased efficiency of 11 beta-hydroxylation of DOC (but not S). This may be due to the activation by ACTH of the zona fasciculata chimeric aldosterone synthase characteristic of this disease. Plasma aldosterone, corticosterone, and DOC concentrations appeared to be more sensitive to ACTH in GSH than in the other groups. The defect in 11 beta-hydroxylation in GSH accounts for the increased levels of DOC reported in this condition and may contribute to the phenotype variability.

Adrenal Cortex Neoplasms↗

Angiotensin II receptors: protein and gene structures, expression and potential pathological involvements.

Two distinct types of cell-surface angiotensin II receptors (AT1 and AT2) have been defined pharmacologically and cDNAs encoding each type have been identified by expression cloning. These pharmacological studies showed the AT1 receptors to mediate all the known functions of angiotensin II in regulating salt and fluid homeostasis. Further complexity in the angiotensin II receptor system was revealed when homology cloning showed the existence of two AT1 subtypes in rodents and in situ hybridization and reverse transcription-polymerase chain reaction analyses showed their level of expression to be regulated differently in different tissues: AT1A is the principal receptor in the vessels, brain, kidney, lung, liver, adrenal gland and fetal pituitary, while AT1B predominates in the adult pituitary and is only expressed in specific regions of the adrenal gland (zona glomerulosa) and kidney (glomeruli). Expression of AT1A appears to be induced by angiotensin II in vascular smooth-muscle cells but is inhibited in the adrenal gland. Preliminary analysis of the AT1 promoters is also suggestive of a high degree of complexity in their regulation. Investigation of a potential role for altered AT1 receptor function has commenced at a genetic level in several diseases of the cardiovascular system. No mutations affecting the coding sequence have been identified in Conn adenoma and no linkage has been demonstrated with human hypertension by sib-pair analysis. None the less, certain polymorphisms that do not alter the protein structure have been found to be associated with hypertension and to occur at an increased frequency in conjunction with specific polymorphisms in the ACE gene in individuals at increased risk for myocardial infarction. Further characterization of the regions of the AT1 gene that regulate its expression are therefore needed. The physiological importance of the AT2 gene product still remains a matter of debate.

Amino Acid Sequence↗

Obesity as a risk factor after combined pancreas/kidney transplantation.

The impact of pretransplant overweight/obesity was analyzed in a group of 268 consecutive primary pancreas renal transplant recipients. Obesity was defined as body mass index (BMI) greater than 27 kg/m2. BMI was available for 240 of the 268 patients. A total of 88% (212/240) of the patients had a BMI < or = 27 and 28/240 (12%) had BMI > 27. There were no significant differences in age, sex, or race between obese and nonobese patients. The incidence and degree of posttransplant hypertension, weight gain, increase in BMI, and hyperlipidemia did not differ on the basis of pretransplant BMI. Serum creatinine at one year posttransplant was slightly increased in obese patients, but the increase was not statistically significant. Cumulative prednisone dose (mg/kg) as well as cyclosporine (CsA) dose (mg/kg) at one year was not significantly different between obese and nonobese patients. However, there was a marginally significant negative correlation between BMI and one-year cumulative (mg/kg) prednisone dose (P = .06). Types and frequency of posttransplant complications were similar between obese and nonobese patients, although there was a slightly higher incidence of wound related complications in obese patients (11% vs. 6.8%) (P = NS). There was no difference in the frequency of acute rejection episodes in obese and nonobese patients. Actuarial patient survival was comparable between patients with BMI < or = 27 versus those with BMI > 27 (P = .10). However, actuarial graft survival, both pancreas and renal, were significantly decreased in patients with BMI > 27 (P = .029). The decrease in pancreas and kidney graft survival in obese patients could not be attributed to decreased "early" patient survival, increased incidence of perioperative or postoperative complications, differences in hypertension, acute rejection episodes, serum lipids, or immunosuppression dosage. The most common causes of graft loss were rejection and patient death in both obese and nonobese patients. After three years posttransplant, the decreased pancreas and renal graft survival in obese patients corresponded to decreased patient survival. The most common cause of patient death was cardiovascular complications in both obese and nonobese PKT recipients.

Adult↗

The prevalence of feline immunodeficiency virus infection in hyperthyroid cats.

One hundred and thirty-four male and female hyperthyroid cats (mean age 11.9 years) were tested for the presence of feline immunodeficiency virus antibodies. Thirty-two (23.9%) were positive. The prevalence of feline immunodeficiency virus antibodies was greater in male cats (30.5%) than in female cats (17.2%). The prevalence of feline immunodeficiency virus infection in hyperthyroid cats is similar to the prevalence of feline immunodeficiency virus in the sick cat population and less than that of sick aged cats at the Massey University Clinic and Hospital. The findings of this survey do not support involvement of feline immunodeficiency virus in the pathogenesis of hyperthyroidism in the cat.

Journal Article↗

Alternatively spliced human type 1 angiotensin II receptor mRNAs are translated at different efficiencies and encode two receptor isoforms.

The peptide hormone angiotensin II (AngII) plays a principal role in regulating blood pressure and fluid homeostasis. Most of its known effects are mediated by a guanine nucleotide-regulatory protein (G protein)-coupled receptor pharmacologically defined as the type-1 AngII receptor or AT1. Characterization of cDNA and genomic clones shows that the human AT1 gene contains five exons and encodes two receptor isoforms as a result of alternative splicing. Exon 5 contains the previously characterized open reading frame for AT1, and exons 1 to 3 are alternatively spliced upstream of it to generate several mRNA species, while transcripts containing exon 4 are of minor abundance. In an in vitro translation system, the presence of exon 1 was found to be extremely inhibitory to translation, probably because it can form a stable secondary structure at the RNA level. The alternatively spliced second exon also had a strong inhibitory effect on translation, presumably because it contains a minicistron commencing with an ATG in an optimal context for translation initiation. Exon 2 was similarly inhibitory to protein production in transfected cells, but exon 1 was found to enhance protein synthesis in this system. Transcripts containing exon 3 and 5, which comprise up to one-third of AT1 mRNAs in all tissues examined, encode a receptor with an amino-terminal extension of 32-35 amino acids. These transcripts were translated into a larger receptor isoform in vitro and produced a functional receptor with normal ligand binding and signaling properties in transfected cells.

Alternative Splicing↗

Reflective practice: a focus for caring.

Nurse education has long been plagued by a perceived disjuncture between theory and practice. This paper explores the use of reflection as a mechanism to enable students of nursing to overcome this problem. A grounded theory approach is used to study a group of first-year students undertaking a 3-year undergraduate nursing course. Results of the study indicate that the use of the reflective processes of clinical debriefing and journaling does impact on the environment, the process, and the focus of learning. Anxiety associated with the learning environment was reduced through peer support and cooperation. In addition, students moved from a passive to a more active mode of learning. The most significant finding was that, over time, reflective processes resulted in the emergence of the client as the central focus of care.

Attitude of Health Personnel↗

Arabidopsis p40 homologue. A novel acidic protein associated with the 40 S subunit of ribosomes.

We have isolated a full-length cDNA clone from Arabidopsis thaliana that has extensive homology to p40 proteins from other organisms. The cDNA predicts a protein (A-p40) of 298 amino acids with a calculated molecular mass of 32.5 kDa and a pI of 4.8. Antibodies raised against an A-p40 fusion protein detected a polypeptide of about 40 kDa in Arabidopsis and about 42 kDa in corn and soybean. In two-dimensional gel electrophoresis the antibodies detected several acidic isoforms. A-p40 appears to be located in the cytoplasm in two forms: soluble, or tightly associated with 40 S subunits and polysomes. Mixing experiments with soluble A-p40 and purified corn polysomes showed that the ribosome-associated form does not result from nonspecific binding during extraction. High concentrations of KCl (1.5 M) are needed to release A-p40 from ribosomes, which suggests that it may be a true ribosomal protein. Several pieces of evidence suggest that A-p40 belongs to the acidic class of ribosomal proteins; first, its acidic pI; second, the presence of amino acid repeats conserved in other acidic ribosomal proteins; and third, the fact that it exists in the cell in two pools (free and ribosome-associated).

Amino Acid Sequence↗