No abstract

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7, 8, 9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between D11S4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers.

In synaesthesia, ordinary stimuli elicit extraordinary experiences. When grapheme-color synaesthetes view black text, each grapheme elicits a photism-a highly specific experience of color. Importantly, some synaesthetes (projectors) report experiencing their photisms in external space, whereas other synaesthetes (associators) report experiencing their photisms "in the mind's eye." We showed that projectors and associators can be differentiated not only by their subjective reports, but also by their performance on Stroop tasks. Digits were presented in colors that were either congruent or incongruent with the synaesthetes' photisms. The synaesthetes named either the video colors of the digits or the colors of the photisms elicited by the digits. The results revealed systematic differences in the patterns of Stroop interference between projectors and associators. Converging evidence from firstperson reports and third-person objective measures of Stroop interference establish the projector/ associator distinction as an important individual difference in grapheme-color synaesthesia.

Measurements on the retention of cigarette smoke constituents in the human respiratory tract have been undertake for more than 100 years. The first studies on nicotine retention were begun by Lehmann in Germany in 1903 and published in 1908. The first studies on the retention of smoke particulate matter were published by Baumbereger in the United States in 1923. Since those early publications, many studies have been undertaken, more or less continuously. This article is a review of the work that has been done over the last 100 years, including a large number of unpublished studies undertaken by British American Tobacco in Southampton, UK. The techniques used have evolved over the years and there is a certain amount of variation in the data. However, the general trends in the results are reassuringly consistent. The bulk of the studies indicate that, on average, 60 to 80% of the mainstream smoke particulate matter is retained in the lungs after inhalation. For nicotine, carbon monoxide, nitric oxide, and aldehydes the total retentions are of the order of 90-100, 55-65, 100, and approximately 90%, respectively, during cigarette smoke inhalation. For most smoke constituents the retentions in the mouth only are considerably smaller than in the whole respiratory tract. The lung retention values for smoke particulate matter are dependent on the depth of inhalation, hold time in the lungs, exhalation volume, and other factors. However, the degree of nicotine retention following inhalation is not markedly influenced by changes in respiratory parameters. Furthermore, the percentage retentions for smoke particulate matter and nicotine are smaller for nonsmoking subjects exposed to environmental tobacco smoke than with active smoking. The smoke retentions are related to properties of the smoke aerosol particles and gases and their behavior as they travel through the respiratory tract. This includes particle growth in the respiratory tract and evaporation of gases out of the particles, and relevant aspects of these processes are also reviewed.