Screening of human primary melanocytes of defined melanocortin-1 receptor genotype: Pigmentation marker, ultrastructural and UV-survival studies

Recent population studies have demonstrated an association with the red-hair and fair-skin phenotype with variant alleles of the melanocortin-1 receptor (MC1R) which result in amino acid substitutions within the coding region leading to an altered receptor activity. In particular, Arg151Cys, Arg160Trp and Asp294His were the most commonly associated variants seen in the south-east Queensland population with at least one of these alleles found in 93% of those with red hair. In order to study the individual effects of these variants on melanocyte biology and melanocytic pigmentation, we established a series of human melanocyte strains genotyped for the MC1R receptor which included wild-type consensus, variant heterozygotes, compound heterozygotes and homozygotes for Arg151Cys, Arg160Trp, Val60Leu and Val92Met alleles. These strains ranged from darkly pigmented to amelanotic, with all strains of consensus sequence having dark pigmentation. UV sensitivity was found not to be associated with either MC1R genotype or the level of pigmentation with a range of sensitivities seen across all genotypes. Ultrastructural analysis demonstrated that while consensus strains contained stage IV melanosomes in their terminal dendrites, Arg151Cys and Arg160Trp homozygote strains contained only stage II melanosomes. This was despite being able to show expression of tyrosinase and tyrosinase-related protein-1 markers, although at reduced levels and an ability to convert exogenous 3,4-dihydroxyphenyl-alanine (DOPA) to melanin in these strains.

A golden age of human pigmentation genetics

The zebrafish golden mutation is characterized by the production of small and irregular-shaped melanin granules, resulting in a lightening of the pigmented lateral stripes of the animal. The recent positional cloning and localization of the golden gene, combined with genotype-phenotype correlations of alleles of its human orthologue (SLC24A5) in African-American and African-Caribbean populations, provide insights into the genetic and molecular basis of human skin colour. SLC24A5 promotes melanin deposition through maturation of the melanosome, highlighting the importance of ion-exchange in the function of this organelle.

Diversity of pigmentation in cultured human melanocytes is due to differences in the type as well as quantity of melanin

Cultured human melanocytes differ tremendously in visual pigmentation, and recapitulate the pigmentary phenotype of the donor's skin. This diversity arises from variation in type as well as quantity of melanin produced. Here, we measured contents of eumelanin (EM) and pheomelanin (PM) in 60 primary human melanocyte cultures (51 neonatal and nine adults), and correlated some of these values with the respective activity and protein levels of tyrosinase, and the melanocortin-1 receptor (MC1R) genotype. Melanocytes were classified into four phenotypes (L, L+, D, D+) as depicted by visual pigmentation using light microscopy, and by the pigmentary phenotype of the donor's skin. There were large differences in total melanin (TM) and EM, which increased progressively for L, L+, D and D+ melanocytes. TM content, the sum of EM and PM, showed a good correlation with TM measured spectrophotometrically, and with the activity and protein levels of tyrosinase. Log EM/PM ratio did not correlate with MC1R genotype. We conclude that: (i) EM consistently correlates with the visual phenotype; (ii) lighter melanocytes tend to be more pheomelanic in composition than darker melanocytes; (iii) in adult melanocyte cultures, EM correlates with the ethnic background of the donors (African-American > Indian > Caucasian); and (iv) MC1R loss-of-function mutations do not necessarily alter the phenotype of cultured melanocytes.

Language disorders in dementia of the Alzheimer type

The language profile of a group of 18 Alzheimer patients is documented and their performance on a standard aphasia test battery compared to a group of institutionalized, nonneurologically impaired control subjects matched for age, sex, and educational level. The Alzheimer patients scored significantly lower than the controls in the areas of verbal expression, auditory comprehension, repetition, reading, and writing. Articulation abilities were the same in each group. A language deficit was evident in all Alzheimer patients. The language disorder exhibited resembled a transcortical sensory aphasia. Syntax and phonology remained relatively intact but semantic abilities were impaired. The results support the inclusion of a language deficit as a diagnostic criterion of Alzheimer's disease.

Review of diagnostic screening instruments for alcohol and other drug use and other psychiatric disorders

In recent years there has been a growing recognition that many people with drug or alcohol problems are also experiencing a range of other psychiatric and psychological problems. The presence of concurrent psychiatric or psychological problems is likely to impact on the success of treatment services. These problems vary greatly, from undetected major psychiatric illnesses that meet internationally accepted diagnostic criteria such as those outlined in the Diagnostic and Statistical Manual (DSM-IV) of the American Psychiatric Association (1994), to less defined feelings of low mood and anxiety that do not meet diagnostic criteria but nevertheless impact on an individual’s sense of wellbeing and affect their quality of life.

Minocycline and oral pigmentation

Minocycline is a semisynthetic tetracycline used in the treatment of inflammatory acne because of its broad spectrum of activity, less common development of resistant organisms, and its anti-inflammatory effects. A number of adverse reactions are reported, including skin and oral pigmentation. This paper details the pharmacology of minocycline and describes the pigmentation and likely mechanisms active in both hard and soft tissues. Oral pigmentation usually involves the hard tissues only and presents typically as a discrete band occupying the central zone of the alveolar mucosa and palate. As with other sites, it may persist following withdrawal of the drug. Early recognition by the dental practitioner may allow an alternative form of therapy to be sought, minimizing the likelihood of a longterm aesthetic problem.

The eyes of deep-sea fish I: Lens pigmentation, tapeta and visual pigments

Deep-sea fish, defined as those living below 200 m, inhabit a most unusual photic environment, being exposed to two sources of visible radiation: very dim downwelling sunlight and bioluminescence, both of which are, in most cases. maximal at wavelengths around 450-500 nm. This paper summarises the reflective properties of the ocular tapeta often found in these animals the pigmentation of their lenses and the absorption characteristics of their visual pigments. Deepsea tapeta usually appear blue to the human observer. reflecting mainly shortwave radiation. However, reflection in other parts of the spectrum is not uncommon and uneven tapetal distribution across the retina is widespread. Perhaps surprisingly, given the fact that they live in a photon limited environment, the lenses of some deep-sea teleosts are bright yellow, absorbing much of the shortwave part of the spectrum. Such lenses contain a variety of biochemically distinct pigments which most likely serve to enhance the visibility of bioluminescent signals. Of the 195 different visual pigments characterised by either detergent extract or microspectrophotometry in the retinae of deep-sea fishes, cn. 87% have peak absorbances within the range 468-494 nm. Modelling shows that this is most likely an adaptation for the detection of bioluminescence. Around 13% of deep-sea fish have retinae containing more than one visual pigment. Of these, we highlight three genera of stomiid dragonfishes, which uniquely produce far red bioluminescence from suborbital photophores. Using a combination of longwave-shifted visual pigments and in one species (Malacosteus niger) a chlorophyll-related photosensitizer. these fish have evolved extreme red sensitivity enabling them to see their own bioluminescence and giving them a private spectral waveband invisible to other inhabitants of the deep-ocean. (C) 1998 Elsevier Science Ltd. All rights reserved.

A survey of contact with offspring and assistance with child care among parents with psychotic disorders

To help improve services for parents with psychotic disorders, patients with such disorders in three treatment agencies in Queensland, Australia, were surveyed about whether they were parents, how much contact they had with their offspring, and who provided assistance with child care. Of the 342 individuals with psychotic disorders mho participated in the study, 124 were parents. Forty-eight parents in the study had children under age 16, and 20 of these parents (42 percent) had their children living with them. Most parents relied on relatives or friends for assistance with child care. Barriers to child care services identified by parents were inability to pay, lack of local services, and fear of losing custody of children.