The language of suicide.
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Attitude to Health↗
Biomedical subjects
G O'Reilly
Publications and source records attributed to G O'Reilly.
Quality assurance programme applied to mobile C-arm fluoroscopy systems.
The importance of quality assurance (QA) of X-ray equipment in diagnostic imaging departments is well recognised. However, practically no attention has been paid in the literature to the application of QA programmes to mobile C-arm fluoroscopy systems. This equipment is sometimes omitted from these programmes because it is often "off-site" from the main radiological facility and suitable QA protocols are unavailable. The need for QA can be substantiated by the fact that these systems are finding greater clinical use in orthopaedic, vascular and cardiac applications. Hence, there is a growing awareness among users for the need of good image quality and low patient radiation dose. In view of this, the objective of this study was to review the existing literature, design a suitable QA protocol for this equipment and use it to survey 10 C-arms in clinical use. The protocol was designed to address mechanical and electrical safety in addition to radiation safety and image quality. Results indicate substantial performance differences between systems with significant variations in input air kerma rate to the image receptor. The authors believe that such a protocol is necessary with a view to establishing optimal performance levels and assist in the development of suitable "write-off" criteria for such systems.
Equipment Safety↗
Expression of endothelin peptides and mRNA in the human heart.
1. We have examined the expression of endothelin isoforms and their precursors in the human heart using RIA, HPLC, immunocytochemistry and reverse transcriptase-polymerase chain reaction assays. 2. Highly specific RIAs were used to measure the levels of mature endothelin and big endothelin-1 immunoreactivity in extracts of human right ventricle. There was no significant difference between samples from patients with ischaemic heart disease and idiopathic dilated cardiomyopathy. 3. HPLC coupled with RIAs allowed the separation and identification of the three mature isoforms of endothelin, big endothelin-1 and the C-terminal fragment of big endothelin-1. In extracts of human endocardial endothelial cells, peaks of immunoreactivity that co-eluted with authentic endothelin-1, big endothelin-1 and C-terminal fragment were found. 4. Intense immunocytochemical staining of mature endothelin immunoreactivity was detected in the cytoplasm of endothelial cells of all regions of the heart tested. Big endothelin-1 immunoreactivity mirrored that of the mature peptide and, in two of three individuals tested, big endothelin-2 immunoreactivity was also detected. No big endothelin-3 immunoreactivity was detected in any of the tissues examined. 5. Reverse transcriptase-polymerase chain reaction assays demonstrated endothelin-1 and endothelin-2 mRNA in all three samples of human left ventricle tested. In two of the individuals, additional bands were also detected with the endothelin-2 primers which corresponded to splice variants. There was no evidence for the expression of endothelin-3 mRNA. 6. These data suggest that endothelin-1 is the predominant isoform of endothelin in the human heart and is probably largely synthesized by the endothelial cells within the heart. If released from the endothelial cells in vivo, this potent cardiotonic peptide may play an important paracrine role in human cardiovascular function.
Adult↗
Intradural lipoma presenting in pregnancy.
Progressive peripheral neuropathy is an unusual condition in pregnancy requiring specialist opinion to identify the possible underlying pathology. The case presented is that of a patient with cervical intradural lipoma and worsening neurological symptoms, treated surgically at the time of caesarean section. This rare disease and its management are discussed.
Adolescent↗
Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ETA sub-type.
1. We measured the ratio of ETA and ETB sub-types in the media (containing mainly smooth muscle) of human cardiac arteries (aorta, pulmonary and coronary), internal mammary arteries and saphenous veins. 2. In saturation experiments, [125I]-endothelin-1 ([125I]-ET-1) bound with high affinity to the media of each vessel (n = 3 individuals or homogenate preparations +/- s.e. mean): coronary artery, KD = 0.14 +/- 0.02 nM, Bmax = 71.0 +/- 21.0 fmol mg-1 protein; pulmonary artery, KD = 0.85 +/- 0.25 nM, Bmax = 15.2 +/- 10.3 fmol mg-1 protein; aorta, KD = 0.51 +/- 0.02 nM, Bmax = 9.4 +/- 4.4 fmol mg-1 protein; internal mammary artery. KD = 0.34 +/- 0.31 nM, Bmax = 2.0 +/- 0.5 fmol mg-1 protein and saphenous vein, KD = 0.28 +/- 0.05 nM, Bmax = 52.8 +/- 1.0 fmol mg-1 protein. In each vessel, over the concentration-range tested, Hill slopes were close to unity and a one site fit was preferred to a two site model. 3. In competition binding assays, the ETA selective ligand, BQ123 inhibited the binding of 0.1 nM [125I]-ET-1 to the media in a biphasic manner. In each case, a two site fit was preferred to a one or three site model: coronary artery, KDETA = 0.85 +/- 0.03 nM, KDETB = 7.58 +/- 2.27 microM, ratio = 89:11%; pulmonary artery, KDETA = 0.27 +/- 0.05 nM, KDETB = 24.60 +/- 5.34 microM, ratio = 92:8%; aorta, KDETA = 0.80 +/- 0.40 nM, KDETB = 2.67 +/- 2.60 microM ratio = 89:11%; saphenous vein, KDETA = 0.55 +/- 0.17 nM, KDETB = 14.4 +/- 0.26 microM, 85:15% (n = 3 individuals or homogenate preparations +/- s.e. mean). BQ123 showed up to 18000 fold selectivity for the ETA over the ETB sub-type. The ETA-selective ligand, [125I]-PD151242 labelled 85% of the receptors detected by a fixed concentration of [125I]-ET-1 in media of internal mammary artery, measured by quantitative autoradiography. In contrast, the density of ETB receptors detected with [125I]-BQ3020 was 7.0 +/- 1.5 amol mm-2, representing about 8% of [125I]-ET-1. 4. A single band corresponding to the expected position for mRNA encoding the ETA receptor (299 base pairs) was found in the media in each of the five vessels (n = 3 individuals) using reverse transcript as epolymerase chain reaction assays. A single band corresponding to the ETB sub-type (428 base pairs) was also always detected.5. 35S-labelled antisense probes to ETA and ETB hybridised to the media of epicardial coronary arteries as well as intramyocardial vessels, confirming the presence of mRNA encoding both sub-types in the vascular smooth muscle of the vessel wall.6 Although mRNA for both receptors was detected, competition binding using BQ123 demonstrated that the majority (at least 85%) of ET receptors present in smooth muscle are the ETA sub-type. These results provide further support for the hypothesis that the ETA sub-type is the receptor that must be blocked in humans to produce a beneficial vasodilatation in pathophysiological conditions where there is an increase in peptide concentration or receptor density.
Adult↗
The Sophy valve and the el-Shafei shunt system for adult hydrocephalus.
A selected series of 22 adult patients with hydrocephalus were treated by a shunt system incorporating a variable pressure Sophy valve or by ventriculojugular shunting against the direction of blood flow using the El-Shafei system. One patient had insertion of two Sophy valves and an El-Shafei shunt. Patient selection was reserved to those with hydrocephalus thought to be at high risk when shunted with systems containing a conventional unipressure valve. None of the eight patients who had ventriculojugular shunting by the El-Shafei method demonstrated any notable clinical or radiological improvement subsequent to shunt insertion. Of the 16 Sophy devices inserted only seven produced a satisfactory result. The current evaluation of shunt malfunction could be improved by support for a national register.
Adolescent↗
ETA and ETB endothelin receptors in human myometrium characterized by the subtype selective ligands BQ123, BQ3020, FR139317 and PD151242.
ETA selective (BQ123, FR139317, PD151242) and ETB selective (BQ3020) ligands were used to define the binding characteristics and contractile function of endothelin receptor subtypes in human myometrium. In saturation binding assays with 10 microns-thick tissue sections [125I]endothelin-1 (ET-1) bound with a single affinity to receptors in the myometrium (Kd, 1.19 +/- 0.17 nM) and adjacent endometrium (Kd, 1.39 +/- 0.51 nM). Competition binding assays in myometrium revealed a heterogeneous population of receptors with BQ123 (Kd ETA, 1.43 +/- 0.33 nM; Kd ETB, 39.91 +/- 9.06 microM), FR139317 (Kd ETA, 2.54 +/- 0.87 nM; Kd ETB, 89.79 +/- 24.34 microM) and BQ3020 (Kd ETA, 4.57 +/- 0.58 microM; Kd ETB, 90.07 +/- 19.53 nM). The presence of these receptors in myometrium was confirmed by saturation assays with the new ETA selective ligand [125I]PD151242 (Kd, 0.93 +/- 0.08 nM; Bmax 138.7 +/- 1.0 fmol/mg protein) and the ETB selective [125I]BQ3020 (Kd, 0.62 +/- 0.07; Bmax 44.5 +/- 1.1 fmol/mg protein). Reverse-transcriptase PCR assays detected mRNA encoding both receptor subtypes in myometrium. Autoradiography with radiolabelled PD151242 and BQ3020 demonstrated that ETA receptors were the predominant subtype in the myometrium and identified a population of ETB receptors in the endometrium. In tissue bath experiments, an ET-1-induced increase in contractility of myometrial strips was antagonized by 10 microM FR139317 but not by BQ123 at the same concentration. The ETB agonist BQ3020, which is a potent agonist in animal tissue, did not increase contractility when tested at concentrations up to 2 microM.
Azepines↗
Quantification of mRNA in human tissue using fluorescent nested reverse-transcriptase polymerase chain reaction.
We report the development of a quantitative nested reverse-transcriptase polymerase chain reaction which utilizes a fluorescence detection system. Using specific primer pairs to study mRNA for endothelin receptors in the human kidney, we synthesized a cRNA construct containing the same sequences but yielding a PCR product some 300 base pairs larger than native mRNA. Inclusion of a known amount of construct as internal standard with tissue RNA prior to cDNA synthesis allowed all reactions to occur under the same conditions in the same tube. In the nested PCR reaction, serial dilutions made before the second round enabled construction of a standard curve for each assay, and confirmation that standard and sample curves remained parallel. This indicates that both cDNAs amplified at the same rate. One internal primer was fluorescently labeled. Quantification of products using an ABI 373A sequencer with Genescan software gave sensitive and reproducible results. Analysis of a needle biopsy (10 mg) of histologically normal cortex gave 0.4 amol ETA mRNA and 1.6 amol ETB mRNA/micrograms total RNA. In medulla these values were 0.46 and 1.16 amol/micrograms, respectively. Ratios of ETB to ETA message were 74:26 in cortex and 77:23 in medulla, agreeing with previous ligand binding studies of receptor protein. Intra- and interassay coefficients of variation were 4.5 and 5.3%. This new method has potential for widespread application to the study of low copy-number mRNA or where only very small amounts of tissue are available, such as biopsy specimens.
Base Sequence↗
Vasoconstrictor endothelin receptors characterized in human renal artery and vein in vitro.
1. We have identified the endothelin receptors present in the media of human main stem renal artery and vein and characterized the subtypes mediating vasoconstriction in these blood vessels in vitro. 2. Messenger RNA encoding both ETA and ETB receptors was identified in the smooth muscle layer of human renal artery and vein by reverse transcriptase-polymerase chain reaction assay. In cryostat-cut cross-sections of both vessels autoradiographical visualisation suggested a majority of ETA receptors. Intense binding was obtained to the non-selective ligand [125I]-ET-1 and the ETA-selective [125I]-PD151242 but only weak labelling of sites by the ETB-selective [125I]-BQ3020. 3. ET-1 potently constricted renal artery and vein preparations with EC50 values of 4.06 nM and 1.00 nM, respectively. Sarafotoxin 6b was approximately ten times less potent than ET-1 with EC50 values of 36.3 nM and 13.8 nM respectively. In the renal artery, ET-3 and sarafotoxin 6c showed little or no activity up to 300 nM. Responses to these peptides were more variable in the renal vein. Preparations from three individuals did not respond to ET-3 but in three further cases, although ET-3 was much less potent than ET-1, full dose-response curves were obtained. S6c elicited dose-related contractions in vein preparations from 5/6 individuals and although more potent than ET-1, the maximum response was 30-60% of that obtained to ET-1. 4. ET-1-induced vasoconstriction of renal artery and vein was antagonized by the ETA-selective, BQ123 (3-10 microM). The dose-response curves to ET-1 were displaced in a parallel rightward fashion with no attenuation of the maximum responses. pA2 values were estimated to be 6.8 +/- 0.1 and 6.8 +/- 0.4 for artery and vein respectively.5. These data suggest that mRNA encoding both ETA and ETB receptors is present in the media of human main stem renal artery and vein. However, autoradiographical studies indicate that the majority of ET receptors expressed are of the ETA subtype. The relative potencies of ET-1 and ET-3 as vasoconstrictors of renal blood vessels in vitro is consistent with this being an ETA-mediated response,and therefore whilst responses to S6c indicate that constrictor ETB receptors may be present in renal veins from some individuals these are likely to be of less importance in these blood vessels.
Adult↗
Trochlear nerve schwannomas: a case report and literature review.
Trochlear nerve sheath tumours are extremely uncommon, only six cases diagnosed during life having been presented previously. In none of these earlier cases were magnetic resonance imaging studies obtained. We report here upon the clinical presentation, surgical management and post-operative course of a case where the diagnosis was suspected pre-operatively from MRI studies. The radiological appearances are described, together with a review of all previously published accounts of this rare tumour.
Adult↗
Lateral parascapular extrapleural approach for single-stage excision of dumb-bell neurofibroma.
An excision of a T1 dumb-bell neurofibroma via a single-stage lateral parascapular extrapleural approach is described. The different surgical approaches that can be used to approach dumb-bell tumours are reviewed, together with the relevant literature.
Humans↗
Alternatively spliced mRNAs for human endothelin-2 and their tissue distribution.
The cDNA for Endothelin-2 (ET-2) has been previously cloned and characterised; however, ET-2 remains the least studied of the endothelin isopeptides and little is known of its function and location. In the present study reverse transcriptase-polymerase chain reaction revealed the presence of seven alternatively spliced mRNA variants encoding ET-2, with a specific pattern of distribution in various human tissues. Computer alignment and analysis of the DNA sequences demonstrated alternative splicing of five exons of 52, 169, 123, 99 and 174 base pairs, in the carboxy terminal region of the mRNA encoding preproET-2. This region contains sites for the post-transcriptional processing of preproET-2 into mature ET-2, therefore we postulate that post-transcriptional processing may be disrupted or altered in these variants.
Alternative Splicing↗
Identification of an actin binding region in aldolase.
Fragmentation of the actin binding glycolytic enzyme, aldolase, with cyanogen bromide yields an 18K actin binding fragment which corresponds to residues 1-164 of the aldolase sequence. Within this fragment there is a region of sequence (residues 32-52) which is highly homologous to a region of sequence near the C-terminus of actin itself and which is also found in the actin binding domains of a number of other actin binding proteins. A synthetic peptide corresponding to the aldolase sequence 32-52 encompassing this region of homology binds to F-actin and specifically competes with native aldolase for binding to this cytoskeletal protein.
Actins↗
Endothelin-2 mRNA splice variants detected by RT-PCR in cultured human vascular smooth muscle and endothelial cells.
Our aim was to examine the hypothesis that vascular smooth-muscle cells (VSMCs) express only ETA mRNA and endothelial cells express only ETB mRNA and to determine which ET mRNA isoforms are expressed in these cell cultures. Using the reverse transcriptase polymerase chain reaction, we were able to detect ETB, ET-1 and splice variant ET-2 mRNA in cultured human umbilical vein endothelial cells (HUVECs) and ETA and splice variant ET-2 mRNA in cultured aortic smooth-muscle cells. The presence of ET-2 mRNA in cultured VSMCs has not been previously reported. These results agree with the hypothesis that ET-1 may be released from vascular endothelial cells to act predominantly on ETA receptors on VSMCs to stimulate contraction of the underlying smooth-muscle cells, and that endothelium-derived relaxing factor release may be mediated predominantly via the ETB receptors on HUVECs. The role of ET-2 expression from HUVECs and VSMCs is less clear.
Base Sequence↗
Human endothelin receptors characterized using reverse transcriptase-polymerase chain reaction, in situ hybridization, and subtype-selective ligands BQ123 and BQ3020: evidence for expression of ETB receptors in human vascular smooth muscle.
Our aim was to characterize and determine the function of endothelin (ET) receptor subtypes in human vascular tissue. Reverse transcriptase-polymerase chain reaction with nested oligonucleotide primers detected the presence of mRNA encoding both ETA and ETB receptors in the media from aorta and pulmonary and coronary arteries. In situ hybridization confirmed the presence of mRNA for both subtypes in the media of coronary arteries. Saturation binding assays using 125I-ET-1 found a single population of high-affinity ET receptors (n = three patients, +/- SEM) in aorta (Kd = 0.507 +/- 0.020 nM; Bmax = 9 +/- 4 fmol/mg protein) and pulmonary (Kd = 0.845 +/- 0.245 nM; Bmax = 15 +/- 10 fmol/mg protein) and coronary arteries (Kd = 0.141 +/- 0.020 nM; Bmax = 71 +/- 21 fmol/mg protein). Using media from coronary arteries, the ETA-selective ligand BQ123 (cyclo[D-Asp-L-Pro-D-Val-L-Leu-D-Trp]) and the ETB-selective ligand BQ3020 (Ala11,15-Ac-ET-1[6-21]) both produced biphasic competition binding curves against 125I-ET-1, confirming the presence of high- and low-affinity sites corresponding to the two subtypes: BQ123 (KdETA = 0.85 +/- 0.03 nM; KdETB = 7.58 +/- 2.27 microM; ETA/ETB, 87%:13%) and BQ3020 (KdETA = 0.22 +/- 0.04 microM; KdETB = 0.77 +/- 0.34 nM; ETA/ETB, 62%:38%). BQ123 (0.1 microM) caused a significant parallel rightward shift of ET-1-induced vasoconstriction of coronary arteries in vitro, but BQ3020 and Ala1,3,11,15-ET-1 failed to show any agonist activity when tested at concentrations of < or = 3 microM in three vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium.
The characterization and localization of endothelin A (ETA) and endothelin B (ETB) receptors have been determined in tissue sections of the human atrioventricular conducting system, surrounding regions of atrial and ventricular myocardium, and the left ventricular free wall by use of radioligand binding, polymerase chain reaction, and in situ hybridization. Selective ETA (BQ123) and ETB (BQ3020) compounds in conjunction with [125I]endothelin-1 revealed the presence of ETA and ETB receptors in the left ventricular free wall (BQ123: 57 +/- 5% ETA, 43 +/- 2% ETB, n = 3; BQ3020: 67 +/- 3% ETA, 33 +/- 3% ETB, n = 3). Autoradiography using [125I]endothelin-1 in the absence or presence of BQ3020, BQ123, or endothelin-1 showed ETA and ETB receptors localized to atrial and ventricular myocardium, the atrioventricular conducting system, and endocardial cells. There was a higher proportion of ETB receptors in the atrioventricular node and the penetrating and branching bundles of His than in the surrounding interventricular and interatrial septa (p < 0.0001). There was a lower density of ETB receptors in the interventricular septum compared with the interatrial septum and the atrioventricular conducting system (p = 0.009) and a lower density of ETA receptors in the atrioventricular conducting system compared with interatrial and interventricular septa (p = 0.008). Isolated right atrial myocytes showed a higher proportion of ETA receptors (91 +/- 12%, n = 3). Amplification of left ventricular free wall cDNA by polymerase chain reaction revealed the presence of ETA and ETB receptor mRNA. mRNA for both subtypes was detected in isolated atrial myocytes. In situ hybridization showed ETA and ETB receptor mRNA localization to atrial and ventricular myocardium, the atrioventricular conducting system, and endocardial cells. These studies demonstrate the presence of ETA and ETB receptors in human myocardium and the atrioventricular conducting system.
Amino Acid Sequence↗
Myelography in the assessment of children with medulloblastoma.
Forty-seven out of 49 patients with a histologically-proven diagnosis of medulloblastoma admitted to our institution between 1 January 1984 and 13 December 1990 were examined post-operatively using either myelography or gadolinium-enhanced magnetic resonance imaging in an attempt to detect clinically occult spinal metastatic disease. Spinal spread of the tumour was identified in nine (19%) patients. Of the 16 patients for whom a 5-year follow-up has been available 12 had no myelographic evidence of spinal disease and of these 10 (83%) remain disease-free. Of the six who have died during this period four had evidence of spinal metastases at presentation. Of all the children in the series with spinal spread identified at the time of their initial hospitalization, only one survives to date (15 months after diagnosis). The remainder had an average life expectancy of 18 months.
Cerebellar Neoplasms↗
Presence of messenger ribonucleic acid for endothelin-1, endothelin-2, and endothelin-3 in human endometrium and a change in the ratio of ETA and ETB receptor subtype across the menstrual cycle.
The aim of the present study was to determine whether mRNA for the three endothelin peptides (endothelin-1, endothelin-2, and endothelin-3) and the two known receptor subtypes (ETA and ETB) was present in human endometrium at different stages of the menstrual cycle (menstrual, early and mid-proliferative, and early, mid-, and late secretory). Endometrium was obtained from women undergoing surgery for benign disease, and total RNA was extracted using a guanidinium isothiocyanate method. mRNA for endothelin peptide and receptor was detected using the reverse transcriptase-polymerase chain reaction with nested oligonucleotide primers. mRNA for endothelin-1, endothelin-2, and endothelin-3 was demonstrated throughout the menstrual cycle, and three splice variants of mRNA encoding endothelin-3 were found in all samples. The ratio of ETA to ETB receptor mRNA was found to change throughout the menstrual cycle. In the proliferative phase, amplified cDNA product was almost exclusively confined to the ETA receptor, whereas an increase in the amplified product of the ETB receptor cDNA was seen in the secretory and menstrual phases. These studies show that mRNA for endothelin-1, endothelin-2, and endothelin-3 is present in human endometrium at all stages of the menstrual cycle and suggest that different physiological actions of the endothelin peptides may be mediated through changes in the ratio of the ETA and ETB receptor subtypes.
Base Sequence↗