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Biomedical subjects

W A Wilson

Publications and source records attributed to W A Wilson.

At least 145 records · Page 8Linked to original sources

Barbiturate enhancement of spike frequency adaptation in Aplysia giant neurons.

Pentobarbital and phenobarbital inhibit repetitive firing of action potentials in neurons of Aplysia by enhancing the normal process of spike frequency adaptation. Voltage clamp studies reveal a slowly developing outward current which is unique to neurons demonstrating spike frequency adaptation. Enhancement of this current by barbiturates was demonstrated and is the probable mechanism by which these drugs enhance adaptation. In experiments in which the pH of the applied drug solutions was altered, barbiturates were more effective in increasing both the slow outward current and adaptation at low pH, suggesting the unionized, acid form, of the drug is responsible for these effects. The concentrations of phenobarbital which were effective closely resembled plasma levels expected to be anticonvulsant.

Action Potentials↗

Diphenylhydantoin enhances early adaptation in Aplysia giant neurons.

Diphenylhydantoin effect on excitability in the molluscan giant neuron was investigated. This model of neuronal excitability was convenient for investigating drug mechanisms because the giant somata of these neurons have multiple current systems and can be voltage clamped. Current and voltage clamp methods were used to quantitate firing frequency and the slow membrane currents associated with changes in firing rate. Diphenylhydantoin enhanced the early rapid deceleration of firing of the cell in response to depolarizing current and blocked an early show inward current.

Action Potentials↗

Plasma haemoglobin and complement activation in sickle cell disease.

The role of haemolysis in producing deficient complement function in homozygous sickle cell disease was studied by measuring indices of complement activation and of haemolysis in 30 asymptomatic patients. Plasma concentration of C3d (an index of increased C3 turnover) was elevated in 40% of patients, and modest decreases in serum concentration of C3 and functionally (haemolytically) active factor B were found. There was a positive correlation between C3d and plasma haemoglobin concentration (r = 0.56, p less than 0.005). Reticulocyte count and foetal haemoglobin concentration also contributed to variation in C3d, though to a lesser extent than plasma haemoglobin. Intravascular haemolysis in sickle cell disease may produce activation of complement and thus cause partial depletion of functional factor B and C3. This may reduce the immune function of the alternative pathway.

Adolescent↗

Prevalence of drug-induced immunologic changes in hypertensive Jamaicans.

Of 137 hypertensive black Jamaicans who took methyldopa for a mean period of 36 months, a positive ANA was found in 1.5% and a positive direct Coombs' test in 0.7%. In 36 patients in whom hydralazine was included in the therapeutic regimen, a positive ANA was seen in only 6%. These results suggest that in black populations, immunologic abnormalities induced by antihypertensive drugs are less common than has been reported in white patients.

Antibodies, Antinuclear↗

Effects of barbiturates on inhibitory and excitatory responses to applied neurotransmitters in Aplysia.

The effects of barbiturates on responses to iontophoretically applied acetylcholine and gamma-aminobutyric acid were studied in Aplysia californica by using a voltage clamp. Dose-response data were obtained for barbiturate concentrations ranging from 1 microM to 3 mM. Both phenobarbital and pentobarbital depress chloride-dependent inhibitory responses to both acetylcholine and gamma-aminobutyric acid. This depression occurs at approximately the same concentrations which attenuate excitatory responses. Potassium-dependent inhibitory responses were minimally affected. In on case was enhancement of inhibitory responses seen, even at concentrations considerably below those which depressed the responses. These results demonstrate that barbiturates can, in some cases, attenuate inhibitory responses to neurotransmitters.

Acetylcholine↗

Dopamine inhibits burst-firing of neurosecretory cell R 15 in Aplysia californica: establishment of a dose-response relationship.

Burst-firing in neurosecretory cell R 15 of Aplysia californica is inhibited by the bath application of dopamine. Voltage-clamp analysis reveals a complex series of changes in the current-voltage relationship of R 15. Dopamine reduces the inward current in the region of negative slope conductance and tends to linearize the current-voltage curve. A variable increase in potassium conductance is frequently observed. The loss of inward current in the region of negative slope conductance is dose-dependent, highly reproducible and relatively resistant to desensitization, and for these reasons a valid dose-response relationship can be described. The dose-response curve is sigmoidal in shape and rises from a minimal effect near 50 microM to a maximal effect near 500 microM. This dose-response curve is useful as a standard of comparison in studies of agonists and antagonists. A protocol for the quantitative study of this system is described, and the constellation of changes in the current-voltage curve produced by dopamine is discussed.

Action Potentials↗

Ocular findings in cytogenetic syndromes.

Several cytogenetic syndromes are reviewed, and the salient ocular and facial abnormalities that might lead to a diagnosis are pointed out. Examples are given of mongoloid slant to the palpebral fissures, not only in Down's syndrome, but also in monosomy 9p, where, in addition, the triangular skull is almost diagnostic. Antimongoloid slant is found in trisomy 9p, where the eyes also have enophthalmos of monosomy 9p. Hypertelorism is another common finding in these syndromes; in monosomy 5p it is almost always present, although it occurs in other conditions as well, including trisomy 12p. The ring 22 syndrome has a distinguishing finding called "doe's eyes" because of the shape of the palpebral fissures. Trisomy 13 has numerous ocular findings as well as skull and facial involvements.

Child↗

Rheumatic disease in Jamaica.

The relative prevalence and clinical pattern of the major rheumatic diseases in the patient population of a teaching hospital in Jamaica were studied over the 3-year period 1974--7. The prevalence of systemic lupus erythematosus approached that of rheumatoid arthritis (RA). All grades of severity of RA were seen, and there was an unusually high proportion of females with RA. Rheumatic fever and exacerbations were relatively common, and in the absence of carditis differentiation from infective polyarthritis, especially gonococcal, was occasionally difficult.

Adolescent↗

Activation of the alternative pathway of human complement by haemoglobin.

Haemoglobin solutions (concentration greater than 1.5 mg/ml), prepared from lysates of erythrocytes from a normal subject and from a patient with sickle cell anaemia, caused factor B and C3 cleavage and loss of haemolytic activity of factor B wehn incubated with fresh autologous serum. Under the same experimental conditions, preparations of erythrocyte stroma or of buffycoat lysates did not produce factor B and C3 cleavage. This reaction required Mg++ but not C1q or C4, indicating that the alternative complement pathway was activated.

Anemia, Sickle Cell↗

Long term followup of cataracts in children after renal transplantation.

In reviewing the course of 218 renal transplantation recipients 55% have developed PSC of which eleven patients have had surgery on one or both eyes; The operations in general have been uncomplicated, and the visual results have been excellent with the exception of one case that had a detached retina. The cataracts were probably induced by heavy corticosteroid therapy as the larger the dosage and the younger the recipient, the more prone were they to the development of lens changes. Phacoemulsification was preferred in this series as the more expeditious technique, leading to a clearer anterior chamber with less chance of developing a secondary cataract.

Adolescent↗

Complement activation in asymptomatic patients with sickle cell anaemia.

Previous reports have suggested that a defect in serum complement may contribute to the increased susceptibility to infection shown by patients with sickle cell anaemia (SCA). In order to define the nature of any complement abnormality in SCA, we investigated the complement system in eighty-seven patients during asymptomatic periods, and analysed factor B turnover in a small sample. In these patients geometric mean serum concentrations of functionally active factor B and factor D, and of C3 and C4 protein (expressed as a percentage of normal reference serum) wer lower than in controls (78% vs 107%, P less than 0.001, 86% vs 103%, P less than 0.001, 91% vs 100%, P less than 0.01, 89% vs 105%, P less than 0.05 respectively). The ratio of the serum concentration of functionally active factor B to factor B protein was lower in patients than in controls (means 75% s.d. 16% vs mean 93%, s.d. 22% P less than 0.001), indicating a functional deficiency of factor B protein. In addition, the fractional catabolic rate of radiolabelled factor B was markedly increased in four out of seven asymptomatic patients studied, and was inversely related to the functional factor B concentration in serum (r = -0.59, P less than 0.05); factor B synthesis was uniformly increased. Complement activation was not related to the presence of circulating C1q binding material. We conclude that complement activation, rather than defective synthesis as previously suggested, contributes to the abnormalities in complement componenet concentration and function in asymptomatic subjects with sickle cell anaemia.

Adolescent↗

Prolonged inhibition in burst firing neurons: synaptic inactivation of the slow regenerative inward current.

By using voltage clamping and microiontophoretic techniques, it has been found that the prolonged cholinergic and dopaminergic inhibition seen in Aplysia burst firing neurons occludes the inward current on which slow oscillations depend. It also mimics the temperature and ionic sensitivity of that inward current. This prolonged inhibition, which cannot be inverted and is insensitive to extracellular potassium changes, thus appears to result from a synaptically produced inactivation of the regenerative slow inward current underlying bursting.

Acetylcholine↗