Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene.

The xeroderma pigmentosum group D (XPD) protein is a subunit of transcription factor TFIIH with DNA helicase activity. TFIIH has two functions, in basal transcription and nucleotide excision repair. Mutations in XPD that affect DNA repair but not transcription result in the skin cancer-prone disorder, xeroderma pigmentosum (XP). If transcription is also affected, the result is the multi-system disorder trichothiodystrophy (TTD), in which there is no skin cancer predisposition, or in rare cases, XP combined with Cockayne syndrome. Up till now there have been no reports of combined clinical features of XP and TTD. We have now identified two patients with some features of both these disorders. One of these, XP189MA, a 3-year-old girl with sun sensitivity, mental and physical developmental delay, has XPD mutations not previously reported, and barely detectable levels of nucleotide excision repair. The other, XP38BR, a 28-year-old woman with sun sensitivity, pigmentation changes and skin cancers typical of XP, has a mutation that has been identified previously, but only in TTD patients with no features of XP. The level of repair of UV damage in XP38BR is substantially higher than that in other patients with the same mutation. With both patients, polarized light microscopy revealed a 'tiger-tail' appearance of the hair, and amino acid analysis of the hair shafts show levels of sulfur-containing proteins intermediate between those of normal and TTD individuals. Our findings highlight the complexities of genotype-phenotype relationships in the XPD gene.

Changes in hair weight and hair count in men with androgenetic alopecia, after application of 5% and 2% topical minoxidil, placebo, or no treatment.

Quantitative estimation of hair growth using hair weight and number was recorded for 120 weeks in 4 groups of 9 men with androgenetic alopecia. Three double-blind groups applied either 2% or 5% minoxidil solution, or vehicle. The fourth group, unblinded, received no treatment. Measurements of hair weight and number were continued for 96 weeks, when treatment (if any) was stopped, though measurements were continued for another 24 weeks. Although not compared statistically, the placebo and untreated groups behaved in a similar fashion. In contrast, the 5% and 2% minoxidil treatment groups showed a statistically significant increase in mean percentage change in interval weight from baseline compared with placebo; results for number counts were usually less significant. Over 96 weeks, topical minoxidil induced and maintained an increase in interval weight over baseline of about 30%. After treatment was stopped, hair weight and number counts for the minoxidil groups returned to about the same levels as placebo in 24 weeks.

Quantitative estimation of hair growth. I. androgenetic alopecia in women: effect of minoxidil.

Quantitative growth of hair over a 40-week period is reported for eight women with androgenetic alopecia. Using a random, double-blind protocol, the women were given either a 2% minoxidil solution or a placebo of vehicle only. Hair in a permanently marked site on the fronto-parietal scalp was pulled through a 1-cm-square clear plastic template, and the outline of the template was drawn on the scalp. The hair was carefully hand clipped and collected at five eight-week intervals (one untreated and four treated), using great care to collect only hairs within the marked area. Subsequent measurements included the total weight of hair grown in the marked area, the total number of hairs, and, on a randomized 50-hair subsample, the weight, lengths, and optical diameters. Calculated quantities included average weight per hair, average length, and average optical width. The average total hair weight of minoxidil-treated subjects increased over the 32-week test period by 42.5%, compared to 1.9% for the placebo-treated subjects (average p = 0.018). Changes for the average number count were 29.9% and -2.6%, respectively (average p = 0.022). These increases, observed using an unusually small number of subjects, clearly distinguished the treated subjects from the untreated. During the same test period, the averaged quantities of weight, diameter, and length from the 50-hair subsample showed insignificant change (p usually greater than 0.5). In addition to showing a larger percentage increase than did the total number, the total weight is not only easier to obtain, but less prone to error during sampling and measurement. Therefore, we recommend that total weight from a defined area be considered as the primary quantitative estimator for hair growth.

Physical and chemical consequences of keratin crosslinking, with application to the determination of crosslink density.

The high levels of covalent disulfide crosslinking in keratins strongly affect (1) structural stability, (2) viscoelasticity, and (3) chemical reactivity. This paper briefly reviews recent work on these subjects, with critical emphasis on methods by which chemical and physical properties can be related to inter-and intra-molecular crosslink density in heterogeneous systems like keratins. Detailed attention is drawn to effects of crosslinking on the hydrolysis of keratin by acids or enzymes. Within the limits of reasonable assumptions, it is possible to account quantitatively for crosslink dependent variations in the hydrolysis rate of different keratins, and also to derive a formula for calculating the absolute intermolecular crosslink density from the amount of keratin dissolved after partial hydrolysis and the number of chain ends appearing in the soluble fraction.