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Biomedical subjects

R Wynn

Publications and source records attributed to R Wynn.

42 records · Page 3Linked to original sources

The hydrophobic core of Escherichia coli thioredoxin shows a high tolerance to nonconservative single amino acid substitutions.

A set of single amino acid substitutions has been constructed at positions Leu42 and Leu78 in the hydrophobic core of Escherichia coli thioredoxin. This protein is required for the in vivo assembly of filamentous bacteriophages such as M13. Almost all the mutants retain this activity regardless of the change in size, hydrophobic nature, or charge of the substitution. Determination of the free energies of unfolding of the mutants containing charged residues shows that these are significantly destabilized as would be expected from simple considerations of the hydrophobic effect. Thioredoxin therefore represents a class of proteins where the often observed correlation between a particular biological activity and thermodynamic stability is not evident for single mutants in the all-or-none assay used. Native thioredoxin is very stable. Thus, structurally single mutants may not perturb the folding equilibrium or the dynamic behavior sufficiently for the effects to be sensed in vivo.

Amino Acids↗

Comparison of two self administered psychiatric questionnaires (GHQ-12 and SRQ-20) in primary care in Chile.

The General Health Questionnaire (GHQ-12) and the Self Report Questionnaire (SRQ-20) were simultaneously validated against the criterion of the Revised Clinical Interview Schedule (CIS-R) in a primary care clinic in Santiago, Chile. A Relative Operating Characteristic (ROC) analysis was used to determine the optimal threshold point for case definition and to compare the performance of these two questionnaires. The validation coefficients for the GHQ-12 and the SRQ-20 were, respectively: sensitivity 76% and 74%; specificity 73% and 77%; overall misclassification rate: 26% and 25%. Misclassification by these questionnaires was significantly associated with education and sex, males being more likely than females to be misclassified as false negatives and poorly educated respondents as false positives. The symptom response profile of both questionnaires showed that the most prevalent items were psychological complaints of anxiety and depression. Both instruments seem to have a similar ability to identify minor psychiatric disorders in primary care in Chile.

Adult↗

Inhibition of human beta-factor XIIa by squash family serine proteinase inhibitors.

Many inhibitors of trypsin and human beta-factor XIIa have been isolated from squash and related seeds and sequenced (Wieczorek et al., Biochem. Biophys. Res. Comm. (1985) 126, 646-652). The association equilibrium constants (Ka) of several of these inhibitors have now been determined with human beta-factor XIIa using a modification of the method of Green and Work (Park et al., Fed. Proc. Fed. Am. Soc. Exp. Biol. (1984) 43, 1962). The Ka's range from 7.8 x 10(4) M-1 to 3.3 x 10(8) M-1. Two isoinhibitors from Cucurbita maxima seeds, CMTI-I and CMTI-III, differ in only a single glutamate to lysine change in the P'4 position. This results in a factor of 62 increase in the Ka of the lysine inhibitor, CMTI-III (Ka = 3.3 x 10(8) M-1). To our knowledge, this is the largest effect ever seen for a residue substitution at the P'4 position of a serine proteinase inhibitor. The result is even more surprising because beta-factor XIIa's natural substrate, Factor XI, contains Gly in the P'4 position.

Amino Acid Sequence↗