Quantal assay

Anthrax Medium from cuitures of B. anthracis 1 Separation of protective antigen from medium 2 Adsorption 3 + 3 quantal assay in guinea-pigs using challenge with B. anthracis Exclusion of live 6. anthracis and of anthrax toxin... 

Diphtheria (adsorbed) Cultures of C. diphtheriae in liquid medium 1 Separation and concentration of toxin 2 Conversion of toxin to toxoid 3 Adsorption of toxoid to adjuvant 3+3 quantal assay in guinea-pigs using intra-dermal challenge Inoculation of guinea-pigs to exclude residual toxin... 

Tetanus (adsorbed) Cultures of Cl. tetani in liquid medium 1 Conversion of toxin to toxoid 2 Separation and purification of toxoid 3 Adsorption to adjuvant 3 + 3 quantal assay in mice using subcutaneous challenge with tetanus toxin Inoculation of guinea-pigs to exclude presence of untoxoided toxin... 

Rabiest Human diploid cell cultures infected with rabies virus 1 Clarification 2 Inactivation with beta-propiolactone 3 + 3 quantal assay in mice Inoculation of cell cultures to exclude live virus... 

Whooping cough Cultures of Bord. 1 Harvest 3 + 3 quantal assay Estimation of... 

The LD50 may be derived graphically from a plot of the probit transform of the incidence of death against the logarithm of the dose administered. This is the classical quantal assay. 

Waud, D. (1972). Biological assays involving quantal responses. J. Pharmacol. Exp. Therap. 183 577-607. 

Synaptic neurotransmission in brain occurs mostly by exocytic release of vesicles filled with chemical substances (neurotransmitters) at presynaptic terminals. Thus, neurotransmitter release can be detected and studied by measuring efflux of neurotransmitters from synapses by biochemical methods. Various methods have been successfully employed to achieve that, including direct measurements of glutamate release by high-performance liquid chromatography of fluorescent derivatives or by enzyme-based continuous fluorescence assay, measurements of radioactive efflux from nerve terminals preloaded with radioactive neurotransmitters, or detection of neuropeptides by RIA or ELISA. Biochemical detection, however, lacks the sensitivity and temporal resolution afforded by electrophysiological and electrochemical approaches. As a result, it is not possible to measure individual synaptic events and apply quantal analysis to verify the vesicular nature of neurotransmitter release. 

Gaddum, J. H. (1933). Methods of biological assay depending on the quantal response. Med Res Counc Ond Sp Rep SerNo 183, London H.M. Stationery Office. 

Miller (1950) has discussed methods of linearization which have been applied to biological assays exhibiting quantal responses. 

We have found that when the whole drug is administered in suspension mice which require doses of 5 and 10 mg for quantal response assays would require doses of 15 and 30 mg when the graded response is to be used. 

The assays fall into two main groups (a) those in which an all or none effect is noted, such as the occurrence of convulsion, death, purgative effect, etc., and which are called quantal response assays and (b) those in which each response is graded in itself such as the measured fall in blood sugar level, or the coagulation time in blood systems, such assays being called continuous response assays. 

The arithmetical treatment of data from both quantal and continuous response assays are essentially the same, the difference lying in that whereas in continuous response assays the variance of a single response is established from the data itself (current or from previous experience), in quantal response assays the variance is established with infinite precision, and in some treatments (probit transformation) varies according to the level of the response. The arithmetic will be greatly reduced if the numbers in each dosage group are equal and the logarithmic interval between the dose levels the same for standard and test. 

For the purpose of example the treatment of a quantal response assay by probit transformation using two doses of standard and two of the test preparation will be considered. The data used are taken from the assay for insulin in which the number of mice displaying hypoglycaemic convulsions is taken as the response. 

The scheme shown can be used for all quantal response assays if probit transformations are to be used. When three doses of standard or test are used and the doses are equally spaced on the logarithmic scale, scores 1,... 

Reference has been made to the essential similarity in the treatment of continuous and quantal response assays. When the response groups are equal in size the treatment as described for the use of angular transformations may be applied using the mean response for the group. In such assays an estimate of variance is established from the data presented and t has the value appropriate to the degrees of freedom with which it is established. When the groups are not equal in size the more extended method used for probit transformations may be used. Each response could... 

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