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Biomedical subjects

M P Birch

Publications and source records attributed to M P Birch.

8 recordsLinked to original sources

Female pattern hair loss, sebum excretion and the end-organ response to androgens.

BACKGROUND: Although female pattern hair loss can be a feature of hyperandrogenism, many women with hair loss show no clinical or biochemical features of androgen excess. It is possible that hair loss in nonhyperandrogenic women is due to a high level of response to androgens by scalp hair follicles. In this study we explored this idea using sebum excretion as a marker of the cutaneous end-organ response to androgens. OBJECTIVES: To test the hypothesis that hair loss in nonhyperandrogenic women is due to an increased cutaneous end-organ response to androgens. METHODS: We studied 100 women, 41 with female pattern hair loss (without hirsutism), 29 with hirsutism (with and without scalp hair loss) and 30 subjects without hair problems. We measured hair density on the frontal scalp, forehead sebum excretion, serum free androgen index (FAI), and body mass index (BMI). RESULTS: The mean FAI was significantly raised in hirsute women compared with nonhirsute women (P < 0.001), but there was no difference in FAI levels between nonhirsute women with and without hair loss. The mean BMI was also significantly elevated in hirsute women (P < 0.01) but there was no difference in BMI between nonhirsute women with and without hair loss. The mean sebum excretion was higher in hirsute women than nonhirsute women but the difference was not statistically significant. There was no difference in sebum excretion between nonhirsute women with and without hair loss. There was no correlation between hair density and sebum excretion. CONCLUSIONS: Our results show that sebum excretion is not elevated in women with female pattern hair loss. This may indicate that different androgen-response pathways operate in controlling hair growth and sebum excretion. The alternative explanation is that nonandrogenic mechanisms are involved in mediating hair loss in some women.

Adolescent↗

Notch4, a non-HLA gene in the MHC is strongly associated with the most severe form of alopecia areata.

Alopecia areata (AA) is a disorder primarily affecting the hair and nails in which associated autoimmune or atopic disease is common. Genetically, it is a complex trait with evidence of a role for genes of the major histocompatibility complex (MHC), the interleukin-1 cluster and chromosome 21 in the pathogenesis. The strongest association is with HLA class II alleles, although whether this indicates a direct contribution to the pathogenesis or results merely from linkage disequilibrium with nearby disease genes is unknown. Notch4 is a recently defined gene in the HLA class III region. Notch signalling is a direct determinant of keratinocyte growth arrest and entry into differentiation. A possible role for Notch in hair growth has been indicated by transgenic mouse findings that activation of the Notch pathway in the hair cortex leads to aberrant differentiation of adjacent hair-shaft layers. Notch4 is therefore a plausible candidate gene for AA. We have examined two polymorphisms in the coding sequence of the Notch4 gene at positions +1297 and +3063 in a case-control study of 116 AA patients and 142 ethnically matched, healthy control subjects. The initial analysis showed a significant association of AA in the overall data set with the Notch4(T+1297C) polymorphism (P<0.001) but not with Notch4(A+3063G). To confirm this association, we genotyped an additional 62 patients and found that the risk for disease was higher in Notch4(+1297C) homozygotes [odds ratio (OR) 3.43 (1.63, 7.19)] than in heterozygotes [OR 2.58 (1.57, 4.24)]. On classifying the patients by severity of disease, the association appeared to be confined to the severest form (alopecia universalis) [OR 4.02 (1.64, 9.88), P=0.0014]. These results support previous findings showing that different HLA susceptibility alleles are associated with mild and severe AA.

Alleles↗

Role of the autoimmune regulator (AIRE) gene in alopecia areata: strong association of a potentially functional AIRE polymorphism with alopecia universalis.

Alopecia areata is characterized by a reversible form of patchy or complete hair loss associated with T-cell infiltration of hair follicles. The lifetime disease risk of approximately 1.4% in the general population is increased to more than 30% in autoimmune polyendocrinopathy candidiasis ectodermal dysplasia syndrome (APECED), a recessive condition resulting from a mutation of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. Aire protein is thought to have transcriptional regulatory activity but its role is not well defined at present. In this study, we have examined the possible involvement of AIRE in the pathogenesis of alopecia areata. On screening the AIRE coding sequence, we identified 20 variants. Two of these at positions, G961C and T1029C, give rise to amino acid changes, S278R and V301A, located in the DNA-binding segment (SAND) and PHD1 zinc finger motif, respectively. We found no difference in the frequency of the AIRE T1029C polymorphism between the control and patient groups. We genotyped 202 alopecia areata patients and 175 matched Caucasian controls for the AIRE G961C alleles. The frequency of the rare allele (961G) was 0.08 in the controls and there was a significant increase to 0.13 in alopecia areata overall and 0.20 in severe disease (alopecia universalis). We found no association between the AIRE G961G variant and mild (patchy) alopecia areata or alopecia totalis. However, the AIRE 961G allele is a potent risk factor (> 3) for the severest form of alopecia areata, and for disease of early age at onset (at 30 years). The change from serine to arginine in the SAND domain of AIRE protein may have a significant effect on AIRE DNA-binding activity. Moreover, our results could provide a rational explanation of the unusually high frequency of AA in APECED patients, supporting the concept of AA as an autoimmune disease.

Adolescent↗

Female pattern hair loss.

Female pattern hair loss is a common condition characterized by a diffuse reduction in hair density over the crown and frontal scalp with retention of the frontal hairline. The prevalence increases with advancing age. It has been widely thought to be the female counterpart of male balding and is often referred to as female androgenetic alopecia. However, the role of androgens is not fully established. Scalp hair loss is undoubtedly a feature of hyperandrogenism in women but many women with female pattern hair loss have no other clinical or biochemical evidence of androgen excess. Female pattern hair loss is probably a multifactorial genetically determined trait and it is possible that both androgen-dependent and androgen-independent mechanisms contribute to the phenotype. In managing patients with female pattern hair loss the physician should be aware that the adverse effects on quality of life can be quite severe and do not necessarily correlate with the objective degree of hair loss. The treatment options are currently limited but modest improvements in hair density are achievable in some women.

Alopecia↗

Hair density, hair diameter and the prevalence of female pattern hair loss.

BACKGROUND: Female pattern hair loss is common but estimates of its prevalence have varied widely. The relationships between the clinical diagnosis of female pattern hair loss and objective measurements of hair density and hair diameter have not previously been evaluated. OBJECTIVES: To determine the prevalence of female pattern hair loss and to relate the clinical findings to hair density and hair diameter. METHODS: We examined 377 women, aged 18--99 years, who presented to a general dermatology clinic with complaints unrelated to hair growth (the unselected sample). A second group of 47 women referred with typical female pattern hair loss was included in analyses of the relationships between hair density, hair diameter and the clinical diagnosis. Hair density was measured using a photographic method. In each subject the major and minor axis diameters were measured in a random sample of 50 hairs. RESULTS: Six per cent of women aged under 50 years were diagnosed as having female pattern hair loss, increasing to 38% in subjects aged 70 years and over. The mean +/- SEM hair density was 293 +/- 61.3 hairs cm(-2) at age 35 years, falling to 211 +/- 55.1 hairs cm(-2) at age 70 years. Hair density showed a normal distribution in the unselected sample. Most women classified as having female pattern hair loss had hair densities within the lower half of the normal distribution. The perception of hair loss was determined mainly by low hair density (ANOVA P < 0.001), but there was overlap in hair density between women classified as having Ludwig I hair loss and the no hair loss group, which was partly accounted for by differences in mean hair diameter (ANOVA P < 0.001). Low hair density was associated with fewer hairs of all diameters. CONCLUSIONS: Hair density in women is distributed as a normal variable, indicating that it is determined as a multifactorial trait. Women with female pattern hair loss have a hair density which falls below the mean but lies within the spectrum of the normal distribution, although other factors, including hair diameter, may affect the subjective impression of hair loss. The hair diameter data suggest that low hair density is not due to progressive diminution in hair follicle size and that follicular miniaturization may occur within the space of a single hair cycle.

Adolescent↗

Reversal set formation in the visually decorticate rat.

Rats given large visual cortex lesions demonstrated a simultaneous task reversal deficit previously reported to follow more extensive cortical ablation. However, no deficit appeared in an operant discrimination that deemphasized visuospatial cues, and the simultaneous task deficit vanished when translucent eye occluders were applied to eliminate spatial, but not intensity, cue use. Because the lesion subjects showed an impairment only when visuospatial cues were available and relevant to correct reversal performance, they seemed hindered by their incompetent processing of visuospatial information. The results are interpreted as support for spatial rather than learning approaches to visual cortex function.

Animals↗

Genetic factors predispose to balding and non-balding in men.

Male pattern balding is a common androgen-dependent trait. The frequency of balding in the population increases with age but not all men develop balding even in old age. It is well-known that balding tends to run in families but the nature of the underlying genetic predisposition and the mode of inheritance are unknown. In this study we examined scalp hair status across a wide age range in 572 men and took family histories of balding in first degree male relatives. The results confirmed that there is an increased frequency of balding in the fathers of young bald men and a high relative risk of balding in young subjects with a balding father but these effects declined with increasing subject age. In contrast, there was a pronounced increase in the frequency of non-balding in the fathers of non-bald elderly subjects and an increased relative risk of non-balding in elderly subjects with a non-bald father, which were not evident in younger subjects. Analysis of the frequencies of balding and non-balding in the brothers of balding and non-balding elderly men, categorised by paternal hair status, failed to show that either balding or non-balding is due to the action of a single gene. Nevertheless, our results indicate that there is a genetic influence on balding in young men and on non-balding in elderly men. It is possible that the same genes are responsible for determining predisposition to balding and to non-balding but, at this stage, we cannot assume that this is necessarily the case. Genetic analysis of balding in young men is complicated by the fact that the destiny of hair status in non-bald siblings is unknown. This difficulty is partly overcome by studying non-balding in elderly men where balding and non-balding in similarly aged siblings are more fully expressed, which may make this age group a better target for future studies in this field.

Adolescent↗