Professor R. H. S. Thompson.
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Biochemistry↗
Biomedical subjects
A D Smith
Publications and source records attributed to A D Smith.
Secretion of acetylcholinesterase and butyrylcholinesterase from the guinea-pig isolated ileum.
1. Strips of longitudinal muscle from guinea-pig ileum, retaining Auerbach's plexus, were superfused with oxygenated Krebs solution. Addition of 50 mM KCl led to a pronounced Ca2+-dependent increase in the activities of both acetylcholinesterase and non-specific cholinesterase (butyrylcholinesterase) in the perfusate but with no change in lactate dehydrogenase activity. 2. No release of acetylcholinesterase, either spontaneous or K+-evoked was observed in tissue freed of the nerve plexus, although release of butyrylcholinesterase still occurred. 3. Carbachol induced a marked Ca2+-dependent increase in the release of acetylcholinesterase but had no effect on the release of butyrylcholinesterase or lactate dehydrogenase. This carbachol-evoked increase in acetylcholinesterase release was blocked by hexamethonium but not by atropine. 4. Four readily soluble molecular forms of acetylcholinesterase and three soluble molecular forms of butyrylcholinesterase were present in innervated longitudinal muscle strips, but insignificant amounts of acetylcholinesterase were detected in denervated strips of muscle. Only one of the four molecular forms of acetylcholinesterase was recovered in the perfusates. 5. It is concluded that acetylcholinesterase is secreted from the nerves of Auerbach's plexus in response to depolarizing stimuli or to nicotinic cholinergic stimulation, while butyrylcholinesterase is secreted from non-neural elements, possibly the longitudinal muscle cells, of guinea-pig ileum in response to a depolarizing stimulus.
Acetylcholinesterase↗
Effects of dietary linoleic acid and gamma linolenic acid on platelets of patients with multiple sclerosis.
The effects of dietary evening primrose oil (rich in linoleic acid and gamma-linolenic acid) were studied on platelets of multiple sclerosis (MS) patients and controls. It was found that platelet aggregation (ADP, thrombin and collagen), platelet fibrinogen binding and platelet glycoprotein (sialic acid and N-acetyl glucosamine) content were not significantly modified by evening primrose oil in MS patients and controls. Moreover, platelet fibrinogen binding and platelet glycoprotein (sialic acid and N-acetyl glucosamine) content were determined for the first time in MS patients and found similar to controls. Platelets of MS patients aggregated more to thrombin and collagen compared to controls, but the difference was only significant with thrombin aggregation after the oil treatment. This study does not show a significant effect of evening primrose oil on platelets of MS patients.
8,11,14-Eicosatrienoic Acid↗
Interlaminar and lateral excitatory amino acid connections in the striate cortex of monkey.
The intrinsic excitatory amino acid pathways within the striate cortex of monkeys were studied by autoradiographic detection of retrogradely labeled somata following microinjections of D-3H-aspartate (D-3H-Asp) into different layers. The labeled amino acid was selectively accumulated by subpopulations of neurons and, to a small extent, by glial cells, the latter mainly in the supragranular layers. Immunocytochemical detection of neurons containing GABA showed that, apart from a few cells exclusively in layer I, GABAergic neurons do not accumulate D-3H-Asp. Several lines of evidence suggest that D-3H-Asp uptake occurred only at nerve terminals; thus, the pattern of perikaryal labeling allowed the delineation of interlaminar and lateral projections. Neurons in layer I probably project laterally, and layer I receives wide-ranging projections from layer IVB and layer V from cells up to 1300 microns laterally. Some neurons in layer II send a focused projection to lower layer VI. Some neurons in layers II/III project up to 1 mm laterally within their own layer, but relatively few neurons can be labeled in these projections. Similarly, in layers II/III few neurons can be retrogradely labeled from layers V and upper VI, and this projection is organized such that cells closer to the pia project deeper in layer V/VI. The connections of layer IVA could not be revealed separately because of the difficulty of confining injections to this thin sublamina. Neurons in layer IVB project up to 1300 microns within IVB itself. A small number of cells from IVB also project to layers III, IVC-alpha, V, and VI with much more restricted lateral spread. Neurons in upper IVC-alpha send axons to layer IVB with at least 600-800 microns lateral spread. Neurons in lower IVC-alpha/upper IVC-beta project to layer III with at least 300-500 microns lateral spread. The bottom 50-80 microns of layer IVC-beta contains neurons with a very focused projection, apparently exclusively to the layer III/IVA border region. Both layers IVC alpha and beta have rich connections within themselves, the beta sublayer having more restricted lateral connections. Some neurons in layer IVC-beta give a laterally restricted small input to layers IVC-alpha and IVB. Both IVC-alpha and -beta project to layers V and VI, and these projections are spread at least 400 microns laterally. Neurons in layer V project to all layers, but the projection to layers I-III and within layer V itself spread much further laterally than the projections to layers IV and VI.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acids↗
Role of phosphoinositol metabolism and phospholipases C and A2/A1 in signal transduction in isolated rat adrenal cells.
Isolated rat adrenal glomerulosa cells were prelabelled with [3H]inositol and stimulated with 25 nM-angiotensin II in the presence of Li+. The resulting inositol monophosphates were separated using h.p.l.c. and 2 major peaks of radioactivity were detected. These showed the same characteristics as inositol 4-phosphate and inositol 1-phosphate and stimulation with angiotensin II increased activity 4-5 fold and 7-8-fold respectively. A minor peak with the characteristics of inositol 1:2 cyclic phosphate increased 1.5-fold after stimulation. No material corresponding to inositol 2-phosphate or inositol 5-phosphate was detected. The results establish the identify of the main inositol phosphate products in angiotensin II-stimulated rat glomerulosa cells. Analysis by h.p.l.c. has been similarly used to assess the inositol phosphates produced after ACTH1-39-stimulation of isolated rat adrenal fasiculata-reticularis cells. A low dose of ACTH1-39 (10(-12) M) stimulated production of small but significant amounts of both glycerophosphoinositol and inositol monophosphate. Using superfused isolated fasiculata-reticularis cells it was also found that ACTH1-39 (10(-9) M and 10(-12) M) rapidly increased efflux of 45Ca+ from 45Ca2+-prelabelled cells. It is concluded that although the results are consistent with a role for phospholipase C in the action of angiotensin II on adrenal glomerulosa cells, in the action of ACTH on adrenal fasciculata-reticularis cells a role for phospholipase A2/A1 is implicated.
Adrenal Glands↗
Studies on blood from patients with dominantly-inherited retinitis pigmentosa.
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Adult↗
Progression of scoliosis in Duchenne muscular dystrophy.
We reviewed the clinical charts and spinal radiographs of fifty-one boys who had Duchenne muscular dystrophy, had not had surgical treatment of the spine, and had been followed until death. All had scoliosis. None of the following variables was useful in predicting which curves would become severe: age when the patient initially walked, age when he ceased walking, age at onset of spinal collapse, surgical release of the iliotibial bands, or age at the time of death. Radiographs were made within eighteen months before death for thirty-three patients; in thirty-one of them, the final curve exceeded 40 degrees and in seventeen, 90 degrees. For the remaining eighteen patients, final radiographs were made more than eighteen months before death; at that time, eight of them already had a curve of more than 90 degrees. Although there was a relationship between extension of the lumbar spine and severity of scoliosis at the time of final follow-up, early maintenance of the lumbar spine in extension rarely prevented the development of a severe curve. For most of the patients who had a severe curve, sitting was difficult and was accompanied by breakdown of the skin and pain. When a patient's curve exceeded 35 degrees, the vital capacity usually was less than 40 per cent of the predicted normal value. Therefore, when walking becomes impossible for boys who have Duchenne muscular dystrophy, routine spinal arthrodesis should be considered.
Adolescent↗
GABA-immunoreactive synaptic boutons in the rat basal forebrain: comparison of neurons that project to the neocortex with pallidosubthalamic neurons.
Although the basal forebrain, including the globus pallidus, contains a high concentration of gamma-aminobutyric acid (GABA), it is not known whether all types of neuron in the globus pallidus receive GABAergic synaptic input. We have studied two types of neuron: typical pallidal neurons that project to the subthalamic nucleus and magnocellular neurons which are found in the medial and ventral borders of the globus and project to the sensorimotor cortex. The postembedding immunogold staining of endogenous GABA revealed many preterminal axons and synaptic boutons that contained GABA immunoreactivity. Neurons that projected to the neocortex were postsynaptic to some of the GABA-immunoreactive boutons, the majority of which formed symmetrical membrane specializations. From a series of random electron micrographs through the perikarya and proximal dendrites of such retrogradely labelled neurons the density of GABA-containing afferent synaptic boutons was estimated to be 0.58 GABA-containing boutons per 100 micron of neuronal membrane. The GABA-containing boutons accounted for 72% of the total afferent input in the proximal regions of the pallidocortical neurons examined. The pallidosubthalamic neurons received many more afferent boutons than did the cortically projecting neurons, a high proportion (80.4%) of which were immunoreactive for GABA. The density of GABA-containing boutons in contact with pallidosubthalamic neurons was 8.9 boutons per 100 micron. It is concluded that cortically projecting basal forebrain neurons, that are probably cholinergic, are innervated by GABA-containing afferent boutons. However, pallidosubthalamic neurons in the same part of the basal forebrain are much more densely innervated by GABA-containing boutons.
Animals↗
Identification of synaptic terminals of thalamic or cortical origin in contact with distinct medium-size spiny neurons in the rat neostriatum.
In order to determine what types of neurons in the striatum receive direct synaptic input from corticostriatal and thalamostriatal fibres and whether these afferents converge on individual striatal neurons, double anterograde labelling of axon terminals was combined with Golgi impregnation at both the light and electron microscopic levels. The area of the central neostriatum that receives input from both the parafascicular nucleus of the thalamus and the somatosensory cortex was identified by retrograde transport of a conjugate of horseradish peroxidase and wheat germ agglutinin (HRP-WGA). The same region of the neostriatum was studied in rats that had received multiple electrolytic lesions in the somatosensory cortex and also an injection of HRP-WGA in different parts of the parafascicular nucleus. Sections of this part of the neostriatum were impregnated by the single-section Golgi procedure after revealing anterogradely transported HRP-WGA. Twelve Golgi-impregnated spiny neurons were recovered and examined in the light and electron microscope after gold-toning. Ten of these neurons were typical very densely spiny medium-size neurons and they were all found to receive asymmetric synaptic input on dendritic spines from degenerating corticostriatal boutons. However, even though numerous boutons labelled anterogradely by HRP-WGA from the parafascicular nucleus were found within the dendritic fields of neurons that received cortical input, none of the terminals from the thalamus made synaptic contact with these neurons. Instead, all 96 thalamostriatal boutons studied were found in asymmetric synaptic contact with dendritic shafts of other neurons. Two such neurons that received input from the parafascicular nucleus were Golgi-impregnated and appeared to be medium-size spiny neurons, but they had a lower density of spines than the typical very densely spiny neurons. An independent confirmation that the targets of thalamostriatal neurons originating in the parafascicular nucleus are dendritic shafts was provided by studying the boutons labelled following electrolytic lesioning or injection of the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) into this nucleus: these boutons were also found to form asymmetric synaptic contacts with dendritic shafts within the neostriatum. It is concluded that although afferents from the somatosensory cortex and from the parafascicular nucleus converge upon the same part of the neostriatum, they probably do not converge upon the same spiny neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Evaluation of the biofragmentable anastomotic ring following preoperative irradiation to the rectosigmoid in dogs.
An animal study was done to evaluate the safety of a sutureless colorectal anastomosis in irradiated bowel. Forty mongrel dogs received preoperative radiation with 5000 rads and then underwent a low anterior resection and anastomosis using either the EEA-31TM stapling device, a two-layer handsewn technique, or the biofragmentable anastomotic ring (BAR) 31-1.5 mm and BAR 31-2.0 mm devices. The anastomoses were then evaluated for early and late anastomotic healing and leaks. The results show four radiographic (three clinical) leaks (P less than .05) in the BAR 31-1.5 mm group and one radiographic leak in the handsewn group. No leaks were detected in the EEA or BAR 31-2.0 mm groups. Results indicate that all three techniques can be done safely with this dose of radiation, and gap size (1.5 mm vs. 2.0 mm) is of critical importance when performing a BAR anastomosis in irradiated bowel.
Anastomosis, Surgical↗
A simple and rapid method for the production of cholera B-chain coupled to horseradish peroxidase for neuronal tracing.
A simple and rapid method is described for the production of cholera B-chain coupled to horseradish peroxidase suitable for neuronal tracing. Horseradish peroxidase was activated with a mild sodium periodate oxidation followed by incubation with the cholera B-chain, to yield the conjugates, samples of which were fractionated further by size exclusion chromatography. Both fractionated material and unfractionated conjugates were tested in vitro by a binding assay on rat synaptic membranes, and in vivo by their ability to undergo retrograde transport following injection into the adrenal medulla of rats. These assays showed that the unfractionated conjugates were equivalent to the fractionated conjugates in binding to the rat synaptic membranes, and that they both provided good retrograde labelling of neurones in the spinal cord after injection into the adrenal medulla, with extensive labelling of the distal dendrites.
Animals↗
Preganglionic sympathetic neurones innervating the rat adrenal medulla: immunocytochemical evidence of synaptic input from nerve terminals containing substance P, GABA or 5-hydroxytryptamine.
Sympathetic preganglionic neurones that innervate the adrenal medulla were identified for subsequent light and electron microscopic study by the retrograde transport of horseradish peroxidase (HRP) or a conjugate of HRP and cholera B-chain. Most labelled neurones were found in the intermediolateral column, but some occurred in the intercalated nucleus and in the lateral funiculus of the thoracic spinal cord. Three morphologically distinct types of neurone were retrogradely labelled, two of which had dendrites that extended medially towards the central canal and laterally across the entire lateral funiculus. A combination of retrograde labelling with pre-embedding immunocytochemistry allowed us to demonstrate synaptic contacts between boutons immunoreactive for substance P or 5-hydroxytryptamine (5-HT) and the cell bodies or proximal dendrites of sympathoadrenal neurones. The 5-HT-immunoreactive boutons appeared to be of two morphologically distinct types. Postembedding immunocytochemistry enabled us to show that sympathoadrenal neurones receive a heavy synaptic innervation from GABA-immunoreactive boutons: 32% of a random series of boutons in synaptic contact with cell bodies were GABA-immunoreactive. Proximal dendrites and also distal dendrites within the white matter were ensheathed in synaptic boutons, 37% of which were GABA-immunoreactive. It is concluded that sympathoadrenal neurones receive at least 4 distinct types of afferent synaptic input: from neurones containing substance P, or GABA and from two types of neurones containing 5-HT. The presence of synaptic inputs on distal dendrites that extend across the white matter adds further complexities to the control of the activity of sympathetic preganglionic neurones.
Adrenal Medulla↗
Complications of endopyelotomy: analysis in series of 64 patients.
We review the complications and failures in our first 64 patients who underwent endopyelotomy. There were 2 intraoperative complications (3.1 per cent) necessitating an open operation. Postoperative complications included leakage around the stent or irritative bladder symptoms, which were treated by repositioning the stent, and 2 instances of ureterovesical stenosis, which have led us to stent the entire ureter in recent cases. There were 7 failures, 4 in patients who in retrospect were not suitable candidates for the percutaneous operation (long stenotic segment and redundant renal pelvis) and 3 for which there was no obvious cause. All failures were apparent soon after removal of the stent that was inserted at the end of the procedure.
Adolescent↗
Endopyelotomy versus open pyeloplasty: comparison in 88 patients.
We compared the results of the first 56 consecutive percutaneous corrections of ureteropelvic junction obstruction (endopyelotomy) at our institution with the most recent 32 consecutive cases of open pyeloplasty. The percutaneous procedure required less time (average 89.4 minutes versus 106.4 minutes for an open operation) and entailed less postoperative pain (60 per cent of the patients required an average of 4.7 unit doses of narcotics, whereas 88 per cent of the pyeloplasty patients required an average of 10.3 unit doses). The average hospital stay was less after endopyelotomy (average 6.2 versus 10.0 days) and return to normal activity occurred more quickly (average 19.8 versus 41.5 days). Endopyelotomy was successful in 87.5 per cent of the patients, with all failures being apparent within 6 weeks and they were easily correctable by traditional methods. Reported success rates of pyeloplasty ranged from 95 to 98 per cent.
Adolescent↗
Management of iatrogenic ureteral strictures after urological procedures.
At our institution more of the iatrogenic ureteral injuries seen are caused by urologists than by gynecologists or general surgeons. The management of 94 such injuries is discussed, 55 of which were the result of open operations, 34 of endourological procedures and 5 of transurethral operations. More than half of the injuries (52 per cent) involved the ureteropelvic junction. Endourological procedures were successful in correcting the problem in 58 patients and consisted of endopyelotomy (38), dilation (10), ureteral meatotomy (8), antegrade ureterotomy (1) and percutaneous ureterotomy (1). Endourological procedures failed in 20 other cases. Altogether, 36 patients (38 per cent) required an open operation consisting of ureteroureterostomy (9), ureterocalicostomy (7), ureteral reimplantation (6), Boari flap (5), pyeloplasty (4), ileal interposition (3), undiversion (1) and nephrectomy (1). The treatment options that appear to be most suitable for particular types of injury are discussed. Final results were satisfactory in all patients.
Dilatation↗
Plasma osteocalcin levels in stone disease. A potential aid in the differential diagnosis of calcium nephrolithiasis.
Plasma osteocalcin levels were measured by radioimmunoassay in 70 consecutive patients with recurrent calcium (sterile) nephrolithiasis during diagnostic evaluation for the cause of the disease. Nephrogenous cyclic adenosine 3,5'-monophosphate levels also were measured in most of the subjects. Included in the sampling, as determined by standard diagnostic criteria, were 12 patients with absorptive hypercalciuria type I, 15 with absorptive hypercalciuria type II, 22 with renal leak hypercalciuria, 11 with normocalciuria, 6 with primary hyperparathyroidism, 3 with renal tubular acidosis and 1 with Paget's disease, as well as 12 control subjects. The observed plasma osteocalcin levels (ng. per ml. mean +/- standard error) were absorptive hypercalciuria I 2.6 +/- 0.20, absorptive hypercalciuria II 3.1 +/- 0.21, renal hypercalciuria 8.7 +/- 0.45, normocalciuric nephrolithiasis 3.3 +/- 0.25, primary hyperparathyroidism 13.2 +/- 0.91, renal tubular acidosis (range) 5.2 to 10.6, Paget's disease 18.0 and control 3.1 +/- 0.20. There were significant differences between the plasma osteocalcin levels of renal hypercalciuria versus primary hyperparathyroidism and renal hypercalciuria/primary hyperparathyroidism versus any other group. There was good correlation between plasma osteocalcin and cyclic adenosine 3,5'-monophosphate data (correlation coefficient 0.72, p less than 0.005). Plasma osteocalcin levels are a potential differential diagnostic tool for patients with stone disease. The diagnostic value compares favorably with that of cyclic adenosine 3,5'-monophosphate, with the advantage that the determination of plasma osteocalcin requires only a single test.
Adult↗
Age differences in encoding specificity.
In two experiments (one under full attention, the other under divided attention), old and young adults were presented with a cued recall task in an encoding specificity paradigm. Targets and associated cues were either pictures or matched words, and there was either a strong or weak semantic relationship between targets and cues. Additionally, cues presented at recall were either the same as or different from those presented at encoding, resulting in four encoding cue--retrieval cue combinations: (a) strong encoding cue and (same) strong retrieval cue; (b) weak encoding cue and (same) weak retrieval cue; (c) weak encoding cue and (different) strong retrieval cue; (d) strong encoding cue and (different) weak retrieval cue. For the most part, the results revealed strong encoding specificity effects for both age groups, as both old and young participants recalled more when the same cues were presented at encoding and retrieval than when different cues were presented. However, when elderly participants received verbal cues under divided attention conditions, evidence for general encoding rather than encoding specificity occurred. Results are discussed in terms of both the encoding specificity principle as well as a more process-oriented interpretation.
Aged↗
Treatment of ureteropelvic strictures with percutaneous pyelotomy: experience in 62 patients.
Percutaneous pyelotomy (endopyelotomy) is an endoscopic technique for the management of ureteropelvic junction obstruction. In a series of 62 consecutive patients, the success rate (measured by symptom-free status and improved uroradiographic findings) was 85%, including both primary and secondary obstructions. All failures were apparent within 3 months of the procedure and required open surgery. There were two major complications during the procedure. Our experience indicates that percutaneous pyelotomy is an effective alternative to traditional open pyeloplasty and has a similar success rate, lower morbidity, and a shorter recovery time.
Adolescent↗