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G O'Reilly

Publications and source records attributed to G O'Reilly.

32 records · Page 2Linked to original sources

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↗

Visual neglect during intracarotid amobarbital testing.

The unilateral suppression of hemispheric function by sodium amobarbital may result in hemispatial visual neglect, as measured by performance on a random letter cancellation task. Our study not only investigates this hypothesis but also attempts to identify more precisely the anatomic locus of control for directed attention to extrapersonal space by correlating scanning performance with EEG activity. Forty-eight consecutive patients with epilepsy underwent preoperative intracarotid amobarbital tests. The results indicated that disruption of scanning and contralateral neglect occurred only after right-hemisphere suppression and seemed specifically related to changes in right frontal lobe EEG activity. This pattern of performance held not only for right-handed subjects, but also for those who were left-handed, and even for those who had right-hemisphere language dominance.

Adolescent↗

A new slide holder for immune staining.

The construction of a Perspex slide holder for use in immune staining is described. The apparatus allows large numbers of slides to be stained at once and makes the procedure less tedious than it would otherwise be.

Immunoenzyme Techniques↗

Limitations of visual assessment of redistribution in thallium images.

Potential limitations of visual assessment of redistribution in thallium (TI) images were studied and results were compared with computer assessment of redistribution. A four-section phantom filled with TI was imaged (300K counts, 128 X 128 matrix) with appropriate background activity and scatter material. Activity in a "defect" section (DS) was varied from 20% to 100% of reference sections (RS). After interpolative background correction, pseudo "initial" and "late" image pairs (N = 35) were photographed on polaroid film and read by three "blinded" observers using an 0-2, 1/2 step, scale (0 = absent and 2 = normal activity). Scan defects were detected by all readers when DS activity was less than or equal to 59% of RS activity. No reader detected a defect when DS activity was greater than or equal to 67% of RS activity. All "initial" defects were detected by computer analysis. Visual assessment of "initial" DS:RS activity ratio did not correlate well with DS:RS activity ratio of the phantom. In contrast, computer assessment of "initial" DS:RS activity ratio correlated well with phantom DS:RS activity ratio (r = 0.96, p less than .0001). Although 22 of 27 scan pairs with partial (N = 26) or full (N = 1) redistribution were correctly identified as showing redistribution by at least two of three observers, the extent of redistribution was not estimated well by visual analysis. Thus, visual assessment of absolute change ("initial"-to-"late") in DS:RS activity ratio showed considerable scatter in relations to actual changes in DS:RS activity ratio of the phantom.(ABSTRACT TRUNCATED AT 250 WORDS)

Computers↗

Role of myocardial ischemia in the genesis of stress-induced S-T segment elevation in previous anterior myocardial infarction.

This study tests the hypothesis that myocardial ischemia is responsible for exercise-induced S-T segment elevation in patients with previous anterior myocardial infarction (MI). Exercise stress testing in conjunction with thallium imaging of the myocardium was performed in 28 patients with previously documented anterior MI. Thallium images were analyzed by computer for the presence of initial uptake defects and evidence of abnormal clearance of the isotope from the myocardium (that is, imaging evidence of ischemia). Total S-T segment elevation (sigma ST) in precordial leads V1 to V6 at rest was subtracted from sigma ST at peak stress in order to quantitate the extent of S-T elevation induced by stress (delta ST). Two groups of patients were identified; 1 with stress-induced S-T elevation (Group I, delta ST greater than or equal to 4.0 mm) and 1 without this abnormality (Group II, delta ST less than 4.0 mm). Evidence of abnormal thallium washout from myocardial scan segments occurred in 12 of 15 Group I patients versus 9 of 13 Group II patients (difference not significant). In addition, abnormal tracer washout from anterolateral or septal scan segments occurred in 5 patients in each group. Likewise, abnormal thallium clearance from inferior or posterior scan segments occurred in 8 of 15 Group I patients versus 7 of 13 Group II patients (difference not significant). The patient with the greatest amount of stress-induced S-T elevation (S-T 11.5 mm) had no evidence of ischemia during the stress test. However, Group I patients did have larger anterolateral plus septal initial thallium uptake defect scores than did those of Group II (10 of 15 with defect score greater than or equal to 350 in Group I versus 1 of 13 in Group II, p less than 0.002). Similarly, resting left ventricular ejection fraction greater than or equal to 30% was present in only 4 of 15 Group I patients versus 13 of 13 in Group II (p less than 0.001). Finally, multiple stepwise linear regression analysis demonstrated that delta ST correlated best with the extent of initial anterolateral plus septal thallium uptake defect score (F = 17.3, p less than 0.001) and to a lesser extent with resting ejection fraction (F = 5.2, p less than 0.05) and change in heart rate from rest to peak stress (F = 8.1, p less than 0.01; corrected multiple correlation coefficient = 0.76, p less than 0.001). Thus, in patients with previous anterior MI (1) exercise-induced myocardial ischemia occurs as often with as without S-T segment elevation, (2) myocardial ischemia is not required for the production of stress-induced S-T segment elevation, and (3) stress-induced S-T elevation primarily reflects the extent of previous anterior wall damage and to a lesser extent an increase in heart rate between rest and peak stress.

Adult↗

Hyperprolactinaemia in males with and without pituitary macroadenomas.

To ascertain whether in hyperprolactinaemic men pituitary macroadenomas represent the end stage of a disease process wherein the only early symptom is impotence, the features of 16 hyperprolactinaemic men with radiological evidence of pituitary macroadenomas were compared with those of 10 hyperprolactinaemic men without pituitary macroadenomas. All were impotent and 25 had low serum testosterone levels. The group with pituitary macroadenoma was older (48.1 vs 63.2 years) and had tolerated impotence for longer (10.4 +/- 6.0 vs 4.5 +/- 2.1 years). 6 of them had visual field defects (none in the other group), 14 had hypopituitarism (1 in the other group), and 14 were initially seen for problems other than sexual dysfunction (whereas all 10 without pituitary macroadenomas were seen primarily for evaluation of recent onset of impotence). In the macroadenoma group bromocriptine restored serum prolactin levels in 13 of the 16 and serum testosterone and potency in 5, whereas in the non-tumour group it restored serum prolactin levels in all 10 and serum testosterone and potency in 9.

Adenoma↗

Carcinoid diathesis of the ileum.

An unusually large number (108) of carcinoids was discovered in the ileum of a 63-year-old male. The clustering and size distribution of tumor nodules suggests that the phenomenon reflects mucosal metastasis from a dominant parent tumor rather than multicentric neoplastic foci. A predilection for the antimesenteric mucosa was also observed and may be related to mucosal lymphatic spread of the carcinoid tumor.

Carcinoid Tumor↗

Mesenteric occlusive lesion and ileal carcinoids.

Occlusion of mesenteric vessels due to fibrosis and adventitial elastosis complicated ileal carcinoids and resulted in infarction of bowel in two patients. Synovial sarcoma antedated the carcinoid syndrome in one patient who died; carcinoma of the breast was discovered one year after hemicolectomy in the other. This rare mesenteric occlusive lesion is associated exclusively with ileal carcinoids; it is poorly recognized and the mortality is high.

Aged↗

Septal lines in pure right heart failure.

Two adult patients are described with pure right heart failure and chronically elevated systemic venous pressure. Neither patient had evidence of pulmonary venous hypertension, but both had septal lines. This unusual finding may be the result of impaired centripetal lymph flow in the lungs due to obstruction of the drainage of the thoracic duct by raised systemic venous pressure.

Adolescent↗

Intraoperative anaphylaxis during neurosurgery.

Intra-operative anaphylaxis is of particular concern in neurosurgery. Not only is there an increased risk of major anaphylaxis, but the frequent placement of patients in the prone or sitting position may make resuscitation difficult. We describe two cases of per-operative anaphylaxis during neurosurgery and the techniques used in the successful management and investigation of these patients.

Adolescent↗

The effects of one month high fructose intake on plasma glucose and lipid levels in non-insulin-dependent diabetes.

The effects of a high fructose diet on the control of blood glucose and serum lipids were studied in 10 non-insulin-dependent diabetic patients (mean age 64.4 years, mean duration of diabetes 5.6 years). Comparison was made following 28 days on the usual diabetic diet and 28 days during which 25% of the usual carbohydrate was substituted with fructose. There was no change in mean (+/- SEM) fasting plasma glucose (on usual diet 9.2 +/- 0.5 mmol/l, on fructose diet, 9.1 +/- 0.4 mmol/l), but there was a fall in mean plasma glucose levels at 30, 60, and 120 min in a 75 g OGTT following the fructose diet. There was no significant change in fasting lipids: on usual diet mean serum cholesterol 5.8 +/- 0.2 mmol/l, on fructose diet 5.6 +/- 0.2 mmol/l; serum triglyceride, on usual diet 1.3 +/- 0.1 mmol/l, on fructose diet 1.3 +/- 0.1 mmol/l; HDL cholesterol on usual diet 1.4 +/- 0.1 mmol/l, on fructose diet 1.4 +/- 0.1 mmol/l. Mean body weight did not vary significantly between the two diets. Incorporation of fructose into the diabetic diet may lower post-prandial glucose levels without disturbing serum lipids.

Aged↗