Study ofL-tryptophan corepressor binding to mutatedE. coli tryptophan repressor proteins by optically detected triplet-state magnetic resonance.

Phosphorescence and optically detected magnetic resonance (ODMR) measurements have been carried out on the tryptophan (Trp) residues ofEscherichia coli Trp repressor protein (W Rep) and its two single Trp-containing mutants, W19F and W99F. The enhanced resolution afforded by the W19F and W99F mutants allowed us to characterize the triplet state of boundL-Trp corepressor using phosphorescence wavelengt-selected ORMR spectroscopy. We find that at 77 K the 0,0 band peak wavelength ofL-Trp is shifted from 405.5 nm in the aqueous solvent to ca. 410 nm when bound to the corepressor binding site. This red shift of the phosphorescence along with a corresponding increase in the zero-field splittingE value and narrowing of the ODMR linewidth characterize a binding site that is less polar, as well as more polarizable and homogeneous, than the aqueous solvent. This conclusion is in agreement with the X-ray crystallographic structure of the holorepressor protein that places the indole chromophore of the bound corepressor in a cleft in which it is sandwiched by the side chains of arginines 54 and 84.

Characterization of the two tryptophan residues of the lactose repressor from Escherichia coli by phosphorescence and optical detection of magnetic resonance.

The native lactose repressor from Escherichia coli (Lac Rep) and two single-point mutants, W220Y and W201Y, were investigated using low-temperature phosphorescence and optical detection of magnetic resonance (ODMR) spectroscopy. Emission from two tryptophan residues was evident in the phosphorescence spectrum of native Lac Rep at 77 K. Using the single-point mutants, the triplet-state properties of tryptophans 201 and 220 were obtained independently. Trp 220 was characterized as a partially solvent-exposed residue (0,0 band centered at 409.5 nm), while tryptophan 201 exhibited the properties of a buried residue (0,0 band centered at 413.5 nm). Both single-point mutant proteins experienced changes in tryptophan triplet-state properties as a result of binding either of two inducer sugars: isopropyl beta-D-thiogalactoside, a monosaccharide, or melibiose, a disaccharide. Putative singlet-singlet energy transfer from tryptophan 220 to tryptophan 201 was also investigated, but the quantitative results must be viewed with some caution.

Cumulative scales for the measurement of agoraphobia.

The questionnaire responses of 559 agoraphobic subjects were analysed to see whether there was a shared hierarchical pattern of fear and avoidance. The items were divided on the basis of a principal component analysis into 13 loading on an Agoraphobia factor and eight on a Claustrophobia factor. When analysed with Guttman Scaling Analysis valid cumulative scales were found for each factor. These scales were replicated in three independent cohorts of subjects and met the most stringent scaling requirements. The scales produced three valid scores of severity for each individual, the first describing exactly which Agoraphobic items the subject avoids, the second describing Agoraphobic items feared and the third Claustrophobic items avoided. Since it is possible to deduce the current pattern of fear and avoidance from the scores, they can be used to summarize the clinical state of an individual client or for making precise descriptive comparisons between agoraphobics . The scales also indicate that agoraphobics do not develop their own unique set of difficulties from the possible pool of problems, but acquire an ordered set of difficulties, the order being shared by other agoraphobics .

Hypnotics and hangovers: a pilot study of chlormezanone in general practice.

Ten patients were included in this pilot study of chlormezanone, assessing its effects on duration and quantity of sleep and daytime performance using a pursuit rotor and a digit symbol test. Comparisons of the sleep assessments favoured chlormezanone, although the differences were not statistically significant. There was no evidence of any reduction in daytime performance after chlormezanone. The comparison of chlormezanone and placebo on the pursuit rotor test and the visual analogue assessment of hangover both slightly favoured the drug, but there were no significant differences. The study has demonstrated that it is feasible to evaluate hypnotic drugs more exactly in general practice.

The epidemiology of fears and phobias in general practice.

Apart from the Agras et al (1969) study, little research has been carried out into the distribution and prevalence of fears and phobias in the general population. It is clear that, during childhood, fears are quite widespread but do not warrant the term 'phobias' although phobias related to school and dentists are exceptions. During adulthood the prevalence of fears and phobias in the general population may be in the region of 76 cases per 1000 although only 2-3% seek psychiatric treatment. This paper reports the preliminary findings of an extensive study into the epidemiology of fears and phobias in 14 general practitioner populations. The most commonly stated fears related to social situations and animals although a wide range of fears were reported. The mean age of onset is 16.3 years, with a male: female ratio of 1:1.7. Fifteen per cent of the sample (n = 110) would like to receive treatment. There is some evidence of nervous disorder in the family but there is no evidence to show that the subjects had an excess of emotional disturbance during childhood. About half the subjects reported that the fear came on for no apparent reason and that they have no effective way of coping with it. Concern was expressed about high levels of anxiety and apprehension, loss of control, fainting, etc., when the subject was in contact with the fear-arousing situation.