Notes: Background  Adrenomedullin (AM) is a regulatory peptide that is synthesized and secreted by a wide number of cells and tissues. AM is a potent vasodilator, but also exerts other functions, such as regulating cell growth and antimicrobial defence. Two receptors, L1 and calcitonin receptor-like receptor (CRLR), which are able to bind AM, have been cloned and characterized.Objectives  To investigate expression of AM protein and its receptors in human skin and during different stages of the human hair cycle and, moreover, because of the suggested antimicrobial function of AM in skin, to investigate AM immunoreactivity (IR) in inflammatory acne lesions compared with healthy pilosebaceous follicles.Methods  We used immunohistochemistry to determine the distribution of AM and its receptors in human skin and during different stages of the human hair cycle. AM IR in inflammatory acne lesions was investigated to evaluate the antimicrobial function of the protein, and hair follicle cultures were performed to examine the role of AM in differentiation and proliferation of hair follicle keratinocytes.Results  Strong IR for AM and its receptors was present in the suprabasal epidermis, in the melanocytes of the epidermis, and in sweat and sebaceous glands. In the hair follicle, AM protein was strongly expressed in the basal and suprabasal layers of the hair bulb and the proximal outer root sheath (ORS). In the distal ORS, AM expression was increasingly suprabasal, especially in proximity to the bulge region where the basal cell layer was free of IR. IR for the CRLR revealed a similar expression pattern to that seen for AM. In contrast, L1 IR showed a suprabasal pattern of IR throughout the ORS. Similar expression of AM and its receptors was observed in catagen and early anagen follicles. AM expression was not markedly upregulated in acne lesions, suggesting a minor role for this antimicrobial peptide in acne. Despite its well-documented mitogenic effects, particularly in oral and skin keratinocytes, AM had no significant effect on hair follicle growth in vitro.Conclusions  AM and its receptors are expressed in human hair follicles, and both AM and its receptors are colocalized in the same compartments and cell types of the skin. This finding is consistent with the proposed autocrine/paracrine mechanism in the physiology of AM.

Notes: Background  Werner syndrome (WS) is a rare autosomal recessive progeroid disorder caused by mutations of the WRN gene encoding a protein of the RecQ-type family of DNA helicases.Objectives  To develop a rapid and simple reverse transcription-polymerase chain reaction (RT-PCR) strategy for mutation analysis of the WRN gene, to identify pathogenic mutations in a German patient with WS and to determine the effects of the pathogenic mutations on WRN mRNA stability.Methods  Allele-specific RT-PCR, semiquantitative RT-PCR, DNA sequencing.Results  We describe a novel and rapid RT-PCR-based method for mutation analysis in WS and report a German patient with WS carrying a previously reported (1396delA) as well as a novel nonsense mutation (2334delAC) of the WRN gene. By semiquantitative RT-PCR analysis we demonstrate that this compound heterozygous genotype leads to WRN transcript decay.Conclusions  In previous studies WS was primarily attributed to a loss of function of stable truncated WRN gene products. Our findings indicate that mutations can also lead to markedly decreased WRN transcript stability.

Notes: Summary Netherton syndrome (NS) is a rare autosomal recessive disease with variable expression. It is defined by a triad of symptoms: congenital ichthyosiform erythroderma, trichorrhexis invaginata and atopy. Recently, genetic linkage has been established to the SPINK5 gene locus on chromosome 5q32 encoding the serine protease inhibitor LEKTI. In this study, we present a recurrent homozygous mononucleotide deletion (153delT) resulting in a severe case of NS exhibiting exfoliative erythroderma with lethal outcome at the age of 4 months and its application in prenatal testing in a subsequent pregnancy of the mother.