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Biomedical subjects

R J Walker

Publications and source records attributed to R J Walker.

359 records · Page 20Linked to original sources
PubMedDate not supplied

Effects of SEPYLRFamide on acetylcholine-induced currents of Helix aspersa neurones: role of ryanodine receptors.

The possible participation of ryanodine receptors in the modulatory effects of the endogenous Helix heptapeptide, SEPYLRFamide, on the acetylcholine-induced currents (ACh-currents) of Helix aspersa neurones was studied using the two-electrode voltage clamp technique. SEPYLRFamide (bath application) caused a reduction of the ACh-currents of D1, D2, F1, F2, F76 and F77 neurones. Ryanodine (10 microM; bath application), which modifies ryanodine-controlled Ca(2+) channels, potentiated the inhibitory effect of SEPYLRFamide on the ACh-current. An antagonist of cyclic adenosine diphosphate ribose (cADPR) and ryanodine receptors, ruthenium red (1 mM; intracellular injection), reduced the inhibitory effects of SEPYLRFamide on the ACh-current. Ryanodine (10 microM) did not change the inhibitory effect of SEPYLRFamide on the ACh-current after intracellular injection of ruthenium red. An agonist of ryanodine receptors, caffeine (5 mM; bath application), reduced the ACh-current. Ryanodine (10 microM) did not change the reduction of ACh-currents induced by the first application of caffeine but decreased the reduction of ACh-currents induced by subsequent applications of caffeine. It is proposed that ryanodine receptors are involved in the inhibitory modulatory effects of SEPYLRFamide on somatic cholinergic receptors of Helix aspersa neurones.

Acetylcholine↗
PubMedDate not supplied

Platelet derived growth factor-BB induced calcium transients in cultured human peritoneal mesothelial cells.

The peritoneal membrane is used as an artificial dialysis organ for patients with end-stage renal failure during continuous ambulatory peritoneal dialysis (CAPD). Resident peritoneal mast cells may influence the course of the inflammatory process during acute infection or prolonged exposure to dialysate in a paracrine fashion, with the release of preformed mediators, including platelet derived growth factor (PDGF), which may activate human peritoneal mesothelial cells (HPMC) and other peritoneal cells. PDGF receptor interactions have multiple intracellular effects, typified by cell proliferation, protein synthesis, cytoskeletal organization, extracellular matrix turnover, and angiogenesis. PDGF may mediate HPMC inflammatory response by stimulating cytokine release. The presence of transcripts for both PDGF-B polypeptide and PDGF-beta receptor in cultured HPMC was confirmed using a reverse transcriptase-polymerase chain reaction. To investigate the activity of PDGF-beta receptors in HPMC, the authors examined intracellular calcium (Ca2+(i)) mobilization in HPMC in response to PDGF-BB (100 ng/ml), histamine (1.0 mmol/L), and 4-brA23187 (1.0 micromol/L) using the calcium indicator, fura-2. HPMC calcium mobilization in response to PDGF was assessed in Krebs-Ringer saline, with and without added external calcium (Ca2+(ext)). HPMC responded to PDGF with a transient rise in Ca2+(i) (approximately 1.6-fold) that returned to an elevated resting value. In the absence of Ca2+(ext), PDGF produced a Ca2+(i) transient indicative of Ca2+ release from intracellular stores. These results suggest that HPMC have functional PDGF-beta receptors that may bind and respond to PDGF in both an autocrine and paracrine

Becaplermin↗
PubMedDate not supplied

The effects of sequential combined oral 17beta-estradiol norethisterone acetate on insulin sensitivity and body composition in healthy postmenopausal women: a randomized single blind placebo-controlled study.

OBJECTIVE: The androgenic effect of progestogen, necessary in early postmenopausal hormone replacement therapy (HRT), may adversely affect insulin sensitivity as well as body fat distribution and thereby increase the cardiovascular risk profile. The impact of HRT with sequential combined oral 17beta-estradiol and norethisterone acetate on insulin sensitivity and body composition in early menopause has not been studied. DESIGN: A randomized single blind placebo-controlled 6-month study of sequential combined 17beta-estradiol norethisterone acetate on insulin sensitivity and body composition was carried out. Thirty fit healthy postmenopausal women were enrolled and completed this 6-month study. Body composition was measured by dual-energy x-ray absorptiometry scanning, and insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp. Studies were undertaken at baseline and after 6 months of therapy. The studies were performed during the estrogen-only phase of therapy. RESULTS: All women demonstrated a degree of decreased insulin sensitivity that was not modified by 6 months of hormone replacement therapy. Body composition remained unchanged over 6 months. There was no alteration in total body fat or the distribution of body fat. The percentage of central abdominal fat (android) was not altered. CONCLUSION: Six months of HRT with sequential combined oral 17beta-estradiol norethisterone acetate does not have an adverse effect on insulin sensitivity and does not promote an increase in weight or the more android distribution of body fat, which could contribute to the increased cardiovascular risk profile that is evident in postmenopausal women.

Absorptiometry, Photon↗
PubMedDate not supplied

Elemental diets in the management of Crohn's perianal fistulae.

Elemental diets have been used extensively in the routine management of patients with Crohn's disease during the past 2 years in this unit. We report our experience in 6 patients in whom perianal fistulae were present. Fistulae improved in 4 patients during elemental feeding; complete healing of fistulae occurred in one of them. No benefit was apparent in 2 patients, but in one the fecal stream had previously been diverted by transverse colostomy, and in the other fecal stasis was marked. The clinical significance of the observations and the difficulties of assessing diet therapy in this condition are discussed.

Adolescent↗
PubMedDate not supplied

Neuropharmacological studies on identified central neurones of the snail, Helix aspersa.

Central neurones of the snail, Helix aspersa, possess both synaptic and somatic receptors to a wide range of classical transmitters and neuroactive peptides. The range of receptors and the type of response is reasonably constant for a specific neurone. This review will provide data concerning the pharmacology of acetylcholine, serotonin, dopamine, noradrenaline, octopamine, glutamate, GABA and purine receptors on identified neurones. Many of these neurones also respond to neuroactive peptides including molluscan peptides, e g, AMPMLRLamide, LSSFVRIamide, SGQSWRQGRPFamide, FMRFamide; coelenterate peptides, e g, pQGRFamide; echinoderm peptides, e g, GFNSALMFamide; and nematode peptides, e g, KNEFIRFamide, KHEYLRFamide, SDPNFLRFamide. Using this data, the pharmacological profiles of identified neurones will be summarised.

Animals↗
PubMedDate not supplied

Supplementation with L-2-oxothiazolidine-4-carboxylic acid, a cysteine precursor, does not protect against lipid peroxidation in puromycin aminonucleoside-induced nephropathy.

Lipid peroxidation in the kidney has been shown to precede proteinuria in puromycin aminonucleoside (PAN)-induced nephropathy. The aim of this study was to determine if L-2-oxothiazolidine-4-carboxylic acid (procysteine) would protect rats against PAN-induced nephrotoxicity. Male Sprague-Dawley rats were treated with procysteine (16 mg/100 g body weight i.p.) 24 h and 30 min prior to receiving a single injection of PAN (15 mg/100 g body weight i.v.) followed by procysteine in the drinking water (4 g/l). Control rats received procysteine alone (intraperitoneally and in drinking water) or PAN alone and then plain water. Proteinuria was not significantly different between PAN/ procysteine and PAN groups, reaching a maximum at day 14 and persisting at day 28. Lipid peroxidation was more severe in PAN/procysteine rats reaching a maximum at day 3 (253 +/- 30 ng/mg protein) compared to day 5 in PAN rats (196 +/- 20 ng/mg protein). Procysteine alone did not modulate proteinuria over 28 days or lipid peroxidation over 7 days. GSH levels over 7 days were not elevated by procysteine and were virtually zero in PAN and PAN/procysteine rats. Focal glomerulosclerosis (FGS) was worse at day 28 in PAN/procysteine rats than in PAN rats (39 +/- 8.2 vs. 23 +/- 4.5%; p < 0.05). This study shows that procysteine as a potential source of reducing equivalents does not protect against renal lipid peroxidation and FGS in this model. On the contrary, PAN/procysteine rats developed significantly more FGS through yet unknown mechanisms.

Administration, Oral↗
PubMedDate not supplied

L-cysteine improves growth of human peritoneal mesothelial cells in vitro.

OBJECTIVE: To improve the growth characteristics of human peritoneal mesothelial cells (HPMC). DESIGN: The effect of commonly used agents, L-cysteine and epidermal growth factor (EGF), added individually ("single") or mixed with hydrocortisone and apo-transferrin ("admixture") in the culture medium (M199) on cultured HPMC, was investigated. METHODS: Growth agents were added to M199 medium along with 2% fetal bovine serum and L-glutamine. Growth was determined by the analysis of thymidine ([methyl-3H] thymidine) incorporation into deoxyribonucleic acid, total cell protein, and by cell counts. Morphology was assessed by phase contrast light microscopy and scanning electron microscopy. RESULTS: HPMC exposed to L-cysteine 0.25 x 10(-3) mol/L (30 micrograms/mL) exhibited significantly improved attachment and growth. Attached cells appeared flat and well spread out shortly after seeding, and produced a tight polygonal monolayer in 14 days, in contrast to the growth of HPMC in control M199 medium, which failed to reach confluence. After an initial lag period in cell growth, EGF (0.01 microgram/mL) produced a greater increase in cell growth than L-cysteine did; however, this was associated with changes in HPMC morphology. During the growth period (14 days), EGF-stimulated HPMC appeared distorted and irregular compared to L-cysteine-treated cells, which had the characteristic tight "cobblestone" appearance. CONCLUSION: L-cysteine improved cell attachment with preservation of the characteristic morphology of HPMC. Epidermal growth factor improved cell growth but produced changes in morphology. The addition of L-cysteine to the culture medium has an important cell growth enhancement role due to the improved cell attachment and cell viability.

Apoproteins↗
PubMedDate not supplied

Predictors of success on the ARRT's MRI exam.

The research described in this article investigated the relationship between selected background variables and the performance of 2546 candidates who took a certification examination in magnetic resonance imaging in 1995. Five variables related to training and experience were investigated: type of training in MR, amount of training in MR, years of experience in MR, hours per week in MR and number of MR scans performed per week. In addition, scores from an entry-level certification exam in general radiography were studied. Results indicated that all six variables were significantly related to MRI exam scores, with prior performance on the radiography exam exhibiting the strongest relationship. Implications of the findings for policy and practice are discussed.

Certification↗
PubMedDate not supplied

Mast cell histamine-induced calcium transients in cultured human peritoneal mesothelial cells.

OBJECTIVE: Peritoneal inflammation results from a complex interplay of events initiated by macrophage activity in response to infection, with the stimulation of mesothelial cell cytokine release amplifying the recruitment of blood-borne defense cells to the site of injury. Resident peritoneal mast cells may add to this complexity with mast cell derived cytokines released during this cascade. This study examined the influence of histamine, a mast cell-derived inflammatory mediator, on the initial activation of human peritoneal mesothelial cells (HPMC) by intracellular free calcium (Ca2+(i)) mobilization, and changes to the actin cytoskeleton. DESIGN: HPMC signal transduction was examined in response to histamine (1.0 mmol/L) compared to fetal bovine serum (FBS) (0.1%) and 4-br-A23187 (1.0 micromol/L). Intracellular free calcium was measured in fura-2 loaded cells with and without external calcium (Ca2+(ext)), or Ca2+(ext) with verapamil (100 micromol/L). Following treatment with agonists, HPMC actin cytoskeleton was stained using direct immunocytochemistry. RESULTS: HPMC responded to histamine with a twofold transient rise in Ca2+(i) which returned to the baseline, in contrast with FBS- and A23187-induced Ca2+(i) transients, which returned to elevated resting values. In the absence of Ca2+(ext), all agents produced a calcium transient indicative of calcium release from intracellular stores. Histamine induced calcium-dependent changes to the cytoskeleton and cellular organization, including increased actin stress fibers. CONCLUSION: Histamine produced large specific receptor-mediated calcium transients in HPMC, which included components of calcium release from intracellular stores and receptor-mediated calcium influx processes. The observed response to histamine raises the possibility that histamine derived from resident mast cells may modulate mesothelial cell function, in part by calcium-dependent pathways, and influence the performance of the peritoneal membrane during peritoneal dialysis.

Calcimycin↗