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Biomedical subjects

P Gates

Publications and source records attributed to P Gates.

At least 37 records · Page 2Linked to original sources

"Quasi-REML" correlation estimates between production and health traits in the presence of selection and confounding: a simulation study.

Performance of the "quasi-REML" method for estimating correlations between a continuous trait and a categorical trait, and between two categorical traits, was studied with Monte Carlo simulations. Three continuous, correlated traits were simulated for identical populations and three scenarios with either no selection, selection for one moderately heritable trait (Trait 1, h2 = .25), and selection for the same trait plus confounding between sires and management groups. The "true" environmental correlations between Traits 2 (h2 = .10) and 3 (h2 = .05) were always of the same absolute size (.20), but further data scenarios were generated by setting the sign of environmental correlation to either positive or negative. Observations for Traits 2 and 3 were then reassigned to binomial categories to simulate health or reproductive traits with incidences of 15 and 5%, respectively. Genetic correlations (r(g12), r(g13), and r(g23) and environmental correlations (r(e12), r(e13), and r(e23)) were estimated for the underlying continuous scale (REML) and the visible categorical scales ("quasi-REML") with linear multiple-trait sire and animal models. Contrary to theory, practically all "quasi-REML" genetic correlations were underestimated to some extent with the sire and animal models. Selection inflated this negative bias for sire model estimates, and the sign of r(e23) noticeably affected r(g23) estimates for the animal model, with greater bias and SD for estimates when the "true" r(e23) was positive. Transformed "quasi-REML" environmental correlations between a continuous and a categorical trait were estimated with good efficiency and little bias, and corresponding correlations between two categorical traits were systematically overestimated. Confounding between sires and contemporary groups negatively affected all correlation estimates on the underlying and the visible scales, especially for sire model "quasi-REML" estimates of genetic correlation. Selection, data structure, and the (co)variance structure influences how well correlations involving categorical traits are estimated with "quasi-REML" methods.

Animal Husbandry↗

Isaac's syndrome: report of a case responding to valproic acid.

Isaac's syndrome is an uncommon, but distressing, condition of spontaneous abnormal muscle activity caused by neuronal hyperexcitability possibly due to damage to slow potassium channels. The underlying aetiology may be peripheral nerve damage from a wide variety of causes, including autoimmune disease. We report a case that failed to respond to carbamazepine or phenytoin but responded dramatically to valproic acid. Thus, valproic acid may be an effective treatment for Isaac's syndrome where these other drugs have failed.

Biopsy↗

Motor nerve biopsy: feasibility and safety.

Motor nerve biopsy was attempted on 19 occasions in 18 patients. Nerve tissue was obtained in 16. The nerves biopsied included those to the anconeus (4 times), palmaris longus (6), flexor sublimus (1), triceps (2), extensor carpi radialis (1), quadriceps (1) and gastrocnemius (1). Attempts to biopsy the radial nerve, the nerve to plantaris and the left common peroneal nerves failed in 2 patients. The lengths of nerve obtained varied from 1 to 3 cm, and from 1-5 fasciculi were present in the specimens. Sufficient material for both electron microscopy and teasing was present in 11. No patient experienced increased weakness, but one had transient paraesthesiae in the distal forearm following biopsy of the nerve to the palmaris longus. We conclude that motor nerve biopsy as described is both feasible and safe. The nerve to the palmaris longus, where that muscle was present, provided the optimum specimen for pathological studies.

Adult↗

Low access resistance perforated patch recordings using amphotericin B.

We present experimental procedures describing the creation of perforated patches by use of amphotericin B. In 13 different cellular preparations, access resistances below 10 M omega were achieved and with blunt electrode tips, access resistances of 3-4 M omega were possible. In addition to using the techniques to measure whole cell currents, we have used them to measure single channel currents in a new "outside-out patch" preparation and we have utilized them to measure the resting voltage of epithelial monolayers. We conclude that these new approaches can provide a substantial increase in versatility and quality for many kinds of electrophysiological measurements.

Amphotericin B↗

Painful sciatic neuropathy following cardiac surgery.

Ten patients developed bilateral asymmetrical lower limb sensori-motor or motor deficits associated with prominent causalgic pain after cardiac surgery. The clinical and electrophysiological abnormalities indicated bilateral proximal sciatic nerve lesions, although in several cases the distinction from a diffuse ischaemic axonopathy was difficult to make. This pattern of postcardiac surgery peripheral neurological dysfunction has not been previously described but is likely to relate either to the intra-operative posturing technique for access to the saphenous veins and/or the upright posture used to nurse patients in the immediate post-operative period and is in keeping with the previously demonstrated susceptibility of peripheral nerves to pressure palsy during cardiac surgical procedures.

Adult↗

Hemitonic seizures: etiological and diagnostic considerations.

Intermittent unilateral tonic posturing of the limbs may relate to focal motor epilepsy, intermittent dystonia or hysteria, and diagnosis may be difficult. Five patients are presented who illustrate two distinct hemitonic syndromes which we believe to be epileptic, namely forced elevation of one arm and paroxysmal hemispasm. It is suggested that these attacks follow an irritative lesion involving the supplementary motor cortex and a deep lesion involving striatothalamic projections respectively. Brevity of episodes, their stereotyped nature and rapid response to anticonvulsant drugs supports an epileptic etiology. The term paroxysmal hemidystonia may not be appropriate for patients with intermittent stereotyped disorders of limb posture, where the clinical features support an epileptic basis and we suggest the designation hemitonic seizures.

Adult↗

Orthostatic tremor: a cause of postural instability in the elderly.

Three cases of a rarely described syndrome of posture-induced tremor of the legs and trunk, which occurs with standing but resolves with walking, sitting and lying, are described. This syndrome occurs in elderly patients and, in the three patients described, responded dramatically to a small dosage of clonazepam.

Aged↗

Electrophysiology of cultured human lens epithelial cells.

The lens epithelial K+ conductance plays a key role in maintaining the lens ionic steady state. The specific channels responsible for this conductance are unknown. We used cultured lens epithelia and patch-clamp technology to address this problem. Human lens epithelial explants were cultured and after 1-4 passages were dissociated and used in this study. The cells from which we measured had a mean diameter of 31 +/- 1 microns (SEM, n = 26). The resting voltage was -19 +/- 4 mV (SEM, n = 10) and the input resistance was 2.5 +/- 0.5 G omega (SEM, n = 17) at -60 mV. Two currents were prominent in whole-cell recordings. An outwardly rectifying current was seen in nearly every cell. The magnitude of this current was a function of K+ concentration and was blocked by 3 mM tetraethylammonium. The instantaneous current-voltage relationship was linear in symmetric K+, implying that the outward rectification was due to gating. The current showed complex activation and inactivation kinetics. The second current seen was a transient inward current. This current had kinetics very similar to the traditional Na+ current of excitable cells and was blocked by 0.1 microM tetrodotoxin. In single-channel recordings, a 150-pS K+ channel and a 35-pS nonselective cation channel were seen but neither account for the macroscopic currents measured.

Adult↗

Potassium channel in rabbit corneal endothelium activated by external anions.

The apical membrane of the rabbit corneal endothelium contains a potassium-selective ionic channel. In patch-clamp recordings, the probability of finding the channel in the open state (Po) depends on the presence of either HCO3- or Cl- in the bathing medium. In a methane sulfonate-containing bath, Po is less than 0.05 at all physiologically relevant transmembrane voltages. With 0 mM [HCO3-]o at +60 mV, Po was 0.085 and increased to 0.40 when [HCO3-]o was 15 mM. With 4 mM [Cl-]o at +60 mV, Po was 0.083 and with 150 mM Cl-, Po increased to 0.36. Low Po's are also found when propionate, sulphate, bromide, and nitrate are the primary bath anions. The mechanism of action of the anion-stimulated K+ channel gating is not yet known, but a direct action of pH seems unlikely. The alkalinization of cytoplasm associated with the addition of 10 mM (NH4)2SO4 to the bath and the acidification accompanying its removal do not result in channel activation nor does the use of Nigericin to equilibrate intracellular pH with that of the bath over the pH range of 6.8 to 7.8. Channel gating also is not affected by bathing the internal surface of the patch with cAMP, cGMP, GTP-gamma-s, Mg2+ or ATP. Blockers of Na/H+ exchange, Na(+)-HCO3- cotransport, Na(+)-K+ ATPase and carbonic anhydrase do not block the HCO3- stimulation of Po. Several of the properties of the channel could explain some of the previously reported voltage changes that occur in corneal endothelial cells stimulated by extracellular anions.

Animals↗

A non-selective cation channel in rabbit corneal endothelium activated by internal calcium and inhibited by internal ATP.

The apical membrane of the rabbit corneal endothelium contains a cation selective channel of 21.7 +/- 0.4 pS conductance which is activated by internal Ca2+ and inhibited by internal ATP. Patch clamp studies show the channel to be quite selective for cations over anions but not to select between Na+ and K+. In excised patches in the inside-out configuration, the open probability increases when the internal Ca2+ is raised above 10(-4) M. ATP decreases the open probability when its internal concentration exceeds 10 microM. At 1 mM ATP, no channel openings are ever seen. AMP and ADP also inhibit at least as well as does ATP. One microM AMP-PNP, a non-hydrolyzable ATP, also inhibits gating and so phosphorylation by a PO4(-3) cleaved from ATP is not the mechanism of ATP inhibition. The channel is apparently impermeable to divalent ions since neither Ba2+ nor Ca2+ carry any detectable current. Quinidine produces a flickery, weakly voltage dependent blockade when applied to the channel's cytoplasmic surface. Both Ca2+ and ATP work at concentrations not expected to occur inside healthy cells. It is presently uncertain if this is a physiologically important channel in these cells.

Adenosine Diphosphate↗

Membrane and junctional properties of dissociated frog lens epithelial cells.

Individual cells and cell pairs were isolated from frog lens epithelium. Individual cells were whole cell voltage clamped and the current-voltage relationship was determined. The cells had a mean resting voltage of -54.3 mV and a mean input resistance of 1.4 G omega. The current-voltage relationship was linear near the cell resting voltage, but showed decreased resistance with large depolarization or hyperpolarization. Junctional currents between pairs of cells were recorded using the dual whole cell voltage-clamp technique. The corrected junctional resistance was 15.5 M omega (64.5 nS). The junctional current-voltage relationship was linear. A combination of ATP and cAMP, in the electrodes, stabilized junctional resistance. Currents recorded when uncoupling was nearly complete, showed evidence of single connexion gating events. A single-channel conductance of about 100 pS was prominent. Dye spread between isolated cell pairs was demonstrated using Lucifer Yellow CH in a whole cell configuration. Photodamage to the cells due to the dye was apparent. Dye loaded cells, in the presence of exciting light, showed decreased resting voltages, decreased input resistances and morphological changes. Glutathione (20 mM) delayed this damage.

Animals↗

Dye and electrical coupling between cells of the rabbit corneal endothelium.

The corneal endothelium is known to contain gap junctions on its lateral borders. Here we show that the endothelial cells of the rabbit cornea are highly dye coupled. Lucifer Yellow CH introduced into a single cell through either an intracellular glass microelectrode or a patch electrode rapidly spreads into its neighboring cells at room temperature. We have used the analysis of Safranyos and Caveney (JCB 100:736-747, 1985) to place quantitative lower bounds on the effective diffusion coefficient of Lucifer Yellow CH iontophoresed into rabbit corneal endothelial cells. By this analysis, we obtain a value of 5.0 x 10(-8) cm2/sec. We also demonstrate that both dye and electrical coupling exists in cell pairs or small clusters of cells enzymatically dissociated from Descemet's membrane.

Animals↗

Intraluminal thrombus in the cerebral circulation. Implications for surgical management.

Thrombi defined as intraluminal filling defects detected by angiography were identified in 30 patients (29 in the carotid system, one in the vertebral artery). Stroke was the presentation ipsilateral to the thrombus in 22 patients (12 had previous transient ischemic attacks), transient ischemic attacks occurred alone in seven cases, and one patient was asymptomatic. Angiography revealed a severe stenosis in association with the thrombus in 23 patients, a moderate stenosis in four patients, and, in the three patients with only minimal stenosis presumably due to atherosclerosis, there was evidence for a coagulopathy. Sixteen of the 30 patients were operated on urgently, 10 within 24 hours of detection of the thrombus. Twelve of these 16 surgical patients were given anticoagulation before surgery. At endarterectomy, thrombus was identified in 11 of the 14 surgical patients in whom the thrombus was accessible; the other two surgical patients had intracranial thrombus only. In this group, four of 11 surgical patients with accessible thrombi suffered perioperative episodes of new or larger infarction. Fourteen of the 30 patients initially received medical management with no complication. Eight of these 14 medical patients had repeat angiography; seven exhibited complete resolution of thrombus, and six of these seven patients subsequently underwent delayed endarterectomy for the stenosis. No thrombus was identified at surgery in any of the six. One of the six delayed surgery patients suffered a perioperative stroke. Although these numbers are small, reflecting the rarity of thrombus demonstrated by angiography, undetected thrombus is often found at endarterectomy. Its presence may increase operative risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Clinically unsuspected cardiac disease in patients with cerebral ischaemia.

In a 6 month prospective study of 232 patients with cerebral ischaemia, 100 (43%) had a prior history of heart disease. In 22 of the patients with prior heart disease an unsuspected cardiac disorder was subsequently detected (6 atrial fibrillation, 13 cardiomegaly or left ventricular hypertrophy and 3 ischaemic heart disease). In patients without prior heart disease, 47 (20%) were found to have cardiac disease: 6 atrial fibrillation, 31 cardiomegaly or left ventricular hypertrophy 9 ischaemic heart disease and 1 left bundle branch block. Previously unsuspected or asymptomatic cardiac disease is common in patients with cerebral ischaemia.

Adult↗