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Results for “Predictive testing”

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At least 487 records · Page 27Linked to original sources
PubMed1991

On the rodent bioassays currently being conducted on 44 chemicals: a RASH analysis to predict test results from the National Toxicology Program.

We use a method of relative potency comparisons to rank the potential strength of 44 compounds being tested in rodent carcinogenicity bioassays. All of our previous hazard evaluations have been for human conditions where great numbers of simultaneous and serial exposures may act in combination to produce a neoplasm comprised of 2(20) to 2(30) cells commonly expected to derive from a single precancerous cell. For human exposures, we have always assumed an initiated target tissue containing at least one transformed but subcarcinogenic cell per organ. Thus, for man we have focused on empirical correspondences that may help to index the monoclonal growth of a particular cell lineage during cancer expansion. In contrast to humans, initiation of target tissues in animals subjected to National Toxicity Program (NTP) bioassays may not be a given condition, because of extensive precautions taken to minimize exposures to contaminates in food, water and cage environments. For this evaluation, we used categorical assignments of 'unlikely', 'possible' and 'probable' carcinogens adapted from NTP tests. Our rank ordering, of compounds according to maximum doses tested in male mice and male rats, is coded accordingly to the three outcomes taken from the NTP tests, but the magnitude of potency depend completely upon our particular method of comparing toxicological data. We have attempted to demonstrate that a relative potency based analysis of a diversity of toxicological data may be useful for rank ordering potentially hazardous compounds to be tested by the NTP and for range-finding of their effective test doses to be administered during chronic test protocols.

Animals↗
PubMed1986

A possible predictive test for graft-versus-host disease in bone marrow graft recipients: the mixed-epidermal cell-lymphocyte reaction.

The possible ability of the mixed-epidermal-cell-lymphocyte reaction (MECLR) to detect alloreactivities in HLA-identical MLR negative siblings has been investigated before grafting in 30 donor-recipients pairs and their families. Results indicate that recipients' epidermal cells (EC) can induce proliferative responses of HLA-identical MLR-negative donors' lymphocytes in 55% of the pairs tested. Moreover, further evaluation of 21 patients shows that the positivity of the MECLR before the graft is correlated with later appearance of acute and chronic GVHD, and especially with the severity of cutaneous injury. EC have been shown to be more efficient antigen presenting cells than peripheral blood lymphocytes for in vitro primary proliferative responses, so these reactions could be directed against some minor histocompatibility antigens, thus leading to possible improvement in selecting bone marrow graft donors and to the detection of donor-recipient pairs with a high risk of GVHD.

Adolescent↗
PubMed2006

Predictive testing for complex diseases using multiple genes: fact or fiction?

PURPOSE: There is ongoing debate about whether testing low-risk genes at multiple loci will be useful in clinical care and public health. We investigated the usefulness of multiple genetic testing using simulated data. METHODS: Usefulness was evaluated by the area under the receiver-operating characteristic curve (AUC), which indicates the accuracy of genetic profiling in discriminating between future patients and nonpatients. The AUC was investigated in relation to the number of genes assumed to be involved, the risk allele frequency, the odds ratio of the risk genotypes, and to the proportion of variance explained by genetic factors as an approximation of the heritability of the disease. RESULTS: We demonstrated that a high (AUC > 0.80) to excellent discriminative accuracy (AUC > 0.95) can be obtained by simultaneously testing multiple susceptibility genes. A higher discriminative accuracy is obtained when genetic factors play a larger role in the disease, as indicated by the proportion of explained variance. The maximum discriminative accuracy of future genetic profiling can be estimated at present from the heritability and prevalence of disease. CONCLUSIONS: Genetic profiling may have the potential to identify individuals at higher risk of disease depending on the prevalence and heritability of the disease.

Area Under Curve↗
PubMed1993

Huntington's disease: predictive testing and the molecular genetics laboratory.

We describe the laboratory-related aspects of a series of 40 completed presymptomatic tests for Huntington's disease, using linked DNA markers. Pedigree structure and marker heterozygosity are shown to be important factors, both in the number of laboratory analyses required to give an informative situation and the residual uncertainty of the final estimate. Specific problems encountered by the testing laboratory are described, with possible ways of avoiding them, and the close links required between laboratory and clinical staff are emphasised.

Adult↗
PubMed1999

Using a radioalloster to test predictions of the cooperativity model for gallamine binding to the allosteric site of muscarinic acetylcholine M(2) receptors.

The muscarinic M(2) receptor contains an orthosteric and an allosteric site. Binding of an allosteric agent may induce a shift alpha of the equilibrium dissociation constant K(D) of a radioligand for the orthosteric site. According to the cooperativity model, the K(A) of alloster binding is expected to be shifted to an identical extent depending on whether the orthosteric site is occupied by the orthoster or not. Here, the novel radioalloster [(3)H]dimethyl-W84 (N,N'-bis[3-(1,3-dihydro-1, 3-dioxo-4-methyl-2H-isoindol-2-yl)propyl]-N,N,N',N'-tetramethyl-1, 6-hexanediaminium diiodide) was applied to directly measure the K(A) shift induced for the prototype allosteric modulator gallamine by binding of N-methylscopolamine (NMS) to the orthosteric site of porcine heart M(2) receptors (4 mM Na(2)HPO(4), 1 mM KH(2)PO(4), pH 7.4; 23 degrees C; data are means +/- S.E.). First, in the common way, the concentration-dependent inhibition by gallamine of [(3)H]NMS equilibrium binding was measured and analyzed using the cooperativity model, which yielded for the affinity of gallamine binding at free receptors a pK(A)= 8.35 +/- 0.09 and a cooperativity factor alpha = 46 (n = 5). The dissociation constant for gallamine binding at NMS-occupied receptors was predicted as p(alpha. K(A)) = 6.69. Labeling of the allosteric site by [(3)H]dimethyl-W84 allowed the measure of competitive displacement curves for gallamine. The K(i) for gallamine at free receptors amounted to pK(i,-NMS) = 8.27 +/- 0.39 (n = 5), which is in line with the prediction of the cooperativtiy model. In the presence of 1 microM NMS, to occupy the orthosteric site, gallamine displaced [(3)H]dimethyl-W84 with pK(i, +NMS) = 6.60 +/- 0.19 (n = 3). Thus, the NMS-induced pK(i) shift amounted to 47, which matches the predicted value of alpha = 46. These results validate the cooperativity model.

Allosteric Site↗