Hairy pinnae after orchiectomy and chemotherapy for testicular cancer: acquired localized hypertrichosis of the ears.

Acquired localized hypertrichosis has rarely been reported. Here, we describe a patient with localized hypertrichosis of the pinnae that occurred 4 months after orchiectomy and chemotherapy for a testicular carcinoma. To our knowledge, this is the first case of an acquired hypertrichosis of the pinnae after cancer therapy. We propose that in our patient either hypogonadism or the hormonal imbalance caused by the cancer therapy led to the development of the hairy pinnae, perhaps alongside a genetic predisposition for hairy ears.

[Status of scalp hair and therapy of alopecia in men in Switzerland]. / Stellenwert der Kopfhaare und Therapie von Haarverlust bei Männern in der Schweiz.

A community-based interview and a questionnaire of men visiting the dermatologist for treatment of hair loss were conducted in Switzerland, to characterize the significance of scalp hair and self-perception of hair loss in Swiss men, and to evaluate current treatment of hair loss. 508 men, aged 15-74 years, regardless of the degree of hair loss, were interviewed by telephone, and 308 patient questionnaires were completed by 19 dermatologists. The questions addressed by the interview were: degree of self-rated hair loss, time invested for hair care, use or reasons for rejecting hair growing agents, relevant criteria for scalp hair, self-assessment with respect to different "hair communication types". The questionnaire analysed the causes of hair loss, prior and current treatment modalities, and follow-up at the dermatologist. Respondents rated their hair loss on a 5-point, textual scale that ranged from 'no hair loss' to 'bald areas'. 43% reported hair loss to some extent. For 42% a full head of hair was very important, especially for men under 29 years, who invested more time for hair care and had not lost hair. Of men with hair loss, 26% previously applied hair growing agents. Of men consulting the dermatologist for hair loss, 90% had androgenetic alopecia. 37% were previously treated: prior treatment was in 59% minoxidil, in 4% finasteride (Propecia), in 7% Aminexil, in 7% dietary supplements, and in 6% conducted by the hair dresser. In 79% treatment was switched to Propecia: of these, 73% adhered to the follow-up consultations at the dermatologist.

Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein.

The epidermal cornified cell envelope (CE) is a complex protein-lipid composite that replaces the plasma membrane of terminally differentiated keratinocytes. This lamellar structure is essential for the barrier function of the skin and has the ability to prevent the loss of water and ions and to protect from environmental hazards. The major protein of the epidermal CE is loricrin, contributing approximately 70% by mass. We have generated mice that are deficient for this protein. These mice showed a delay in the formation of the skin barrier in embryonic development. At birth, homozygous mutant mice weighed less than control littermates and showed skin abnormalities, such as congenital erythroderma with a shiny, translucent skin. Tape stripping experiments suggested that the stratum corneum stability was reduced in newborn Lor(-/-) mice compared with wild-type controls. Isolated mutant CEs were more easily fragmented by sonication in vitro, indicating a greater susceptibility to mechanical stress. Nevertheless, we did not detect impaired epidermal barrier function in these mice. Surprisingly, the skin phenotype disappeared 4-5 d after birth. At least one of the compensatory mechanisms preventing a more severe skin phenotype in newborn Lor(-/-) mice is an increase in the expression of other CE components, such as SPRRP2D and SPRRP2H, members of the family of "small proline rich proteins", and repetin, a member of the "fused gene" subgroup of the S100 gene family.

Monosymptomatic Loa loa infection.

We report the case of a 17-year-old student from Cameroon who presented an atypical, mono-symptomatic form of Loa loa infection, characterized only by rare subcutaneous movements of adult worms.

Norwegian scabies in a patient with acquired immunodeficiency syndrome.

We report the case of a 42-year-old man with symptomatic HIV infection (C3 CDC stage) who presented widespread hyperkeratotic skin lesions diagnosed as Norwegian scabies. The CD4 count was 87 cells/mm3. The patient has been the source of a nosocomial outbreak (20 individuals affected). He was treated successfully with combined topical treatment (permethrin 5% cream plus keratolytic agents) and oral ivermectin.

Apocrine cystadenoma, apocrine hidrocystoma, and eccrine hidrocystoma: three distinct tumors defined by expression of keratins and human milk fat globulin 1.

Eccrine hidrocystomas and apocrine cystadenomas are morphologically related cystic sweat gland tumors. To elucidate their cellular differentiation we examined by immunohistochemistry the expression of keratins and of human milk fat globulin 1 in 12 of each of these tumors, diagnosed using established conventional histological criteria. All tumors diagnosed as apocrine cystadenomas by these criteria were characterized by a keratin pattern of secretory type. In addition, they expressed human milk fat globulin 1. Tumors diagnosed as eccrine hidrocystomas expressed a keratin pattern of excretory type. A part of the tumors with an excretory keratin pattern expressed human milk fat globulin, while others did not. Some presumed eccrine hidrocystomas expressed the very same antigens as apocrine cystadenomas. Thus, our study reveals three distinct types of tumors, in contrast to the conventional distinction of only eccrine hidrocystomas and apocrine cystadenomas. Apocrine cystadenomas differentiate towards the secretory coil of apocrine sweat glands. Presumed eccrine hidrocystomas may represent cystic tumors of the eccrine sweat duct, or they may represent cystic tumors of the apocrine duct. Thus, the name hidrocystoma should be used without further specification of an eccrine or apocrine nature, unless certainty is reached by immunohistochemical characterization. Also, hidrocystomas often prove to be histologically misdiagnosed apocrine cystadenomas because of a flattened cyst wall secondary to increased intraluminal pressure.

Congenital alopecia areata.

Alopecia areata has never been documented in a newborn. Thus, it is generally assumed that alopecia areata is acquired only postnatally, and it is believed that the presence of an alopecia at birth virtually excludes its diagnosis. In this report we document a case of alopecia areata in a premature newborn.

The small proline-rich proteins constitute a multigene family of differentially regulated cornified cell envelope precursor proteins.

Loricrin, involucrin, small proline-rich protein (SPRR)1, SPRR2, and SPRR3 genes are located within a cluster of 1.5 Mbp on chromosome 1q21 and most likely evolved from a common ancestor. Monospecific polyclonal antibodies and cDNA probes were produced to investigate SPRR transcripts and proteins. SPRR expression was restricted to terminally differentiating squamous cells, preferentially located at the cell periphery, and immunoreactivity was greatly reduced in cells with a mature cornified cell envelope. Furthermore, detectable SPRR2 and SPRR3 levels were strongly increased in differentiating keratinocyte cultures after addition of LTB-2, a specific inhibitor of transglutaminases, suggesting that they are precursor proteins of the cornified cell envelope. In normal epidermis, SPRR1 was restricted to appendageal areas, SPRR2 was expressed coherently, and SPRR3 was completely absent. In the upper digestive tract, SPRR1 was expressed in sublingual and tongue epithelium, SPRR2 was mostly restricted to lingual papillae, and SPRR3 was abundant in oral and esophageal epithelium. In psoriatic epidermis, SPRR1 and SPRR2 were expressed at much higher levels than in normal epidermis. Addition of 10(-7) M retinoic acid to cultured differentiating keratinocytes significantly down-regulated the expression of SPRR2 and SPRR3 transcripts and slightly decreased that of SPRR1. Thus, SPRR1, SPRR2, and SPRR3 are differentially expressed in vivo and in vitro, suggesting that the SPRR multigene family evolved to serve as highly specialized cornified cell envelope precursor proteins in stratified epithelia.

Human scalp hair follicle development from birth to adulthood: statistical study with special regard to putative stem cells in the bulge and proliferating cells in the matrix.

The depths of hair follicle compartments, and in particular of the bulge, the putative site of hair follicle stem cells, have not yet been determined in human scalp skin from infants, children or adolescents. This information is necessary in order to use the scalp safely as a donor site for skin grafts. We therefore investigated the development of the infundibulum, the bulge, Adamson's fringe, the B-fringe and the matrix by measuring the depths of these five follicular compartments in parietal scalp biopsy specimens from 100 patients ranging in age from 2 weeks to 21 years. The thickness of the epidermis and the dermis were also assessed. The correlations of these measurements with age were determined by regression analysis. The regression equation for the bulge was found to be b (microns) = 683.3 + 30.8y (r = 0.73; SEM = 145.5) where y is the age in years, and for the matrix it was m (microns) = 1616.2 + 90.4y (r = 0.76; SEM = 406.5); P < 0.0001 for the null hypothesis. The growth of the inferior portion below the bulge was not parallel but proportional to that of the superior portion. The relative position of the bulge in the dermis was stable, whereas the inferior portion moved progressively more deeply into the subcutis. These findings provide evidence for the postulated biologically advantageous localization of the bulge, and thus is a further argument in favour of the bulge as the site of follicular stem cells.

The 'mantle hair of Pinkus'. A review on the occasion of its centennial.

The 'mantle hair' is a hair follicle which is characterized by a circumferential proliferation of basaloid epithelial cells emanating from the base of its infundibulum. These cells show varying sebaceous differentiation. The mantle hair was first described 100 years ago. Since then, this type of hair follicle with its particular sebaceous gland has been forgotten repeatedly, to be rediscovered anew. Thus, a confusing terminology has evolved, and concepts of its nature are controversial. In this article we present a review of the 100-year history of the mantle hair.

Involucrin mRNA is more abundant in human hair follicles than in normal epidermis.

Involucrin is a precursor protein of the cornified cell envelope in epidermal keratinocytes, where it has been located by immunohistochemistry in the upper spinous and granular layers of human epidermis. In the hair follicle, involucrin has been found in the inner root sheath and in the upper layers of the infundibulum and the isthmus (upper outer root sheath), whereas its presence in the lower outer root sheath and the cortex has been controversial. Therefore, we analyzed the distribution of involucrin mRNA in adult scalp by Northern blotting and in situ hybridization. Northern blots showed more abundant involucrin mRNA in the follicular fraction than in the epidermal fraction of dissected scalp. In situ hybridization matched the immunohistologic results; transcripts of involucrin were expressed not only in the infundibulum and isthmus, but also in the hair cortex and medulla, in all layers of the inner root sheath, and in the inner cells of the lower outer root sheath (all of which lack a cell envelope at the ultrastructural level). However, involucrin was absent in the hair cuticle, which is the only compartment of the follicle possessing a morphologically distinct cell envelope. Our results suggest, first, that involucrin does not serve as a precursor protein of the cornified cell envelope in adult hair follicles, and second, that it is perhaps not necessary for the formation of the cell envelope in keratinocytes of the hair cuticle, as we did not find this precursor protein with highly sensitive methodology.

p53 protein in benign and malignant sweat gland tumors.

Mutation of the p53 gene and increased levels of p53 protein are among the most frequent alterations in human cancers. To date, very little is known about the mechanisms underlying the development of sweat gland carcinomas. In this study, we analyzed 43 benign and 39 malignant sweat gland tumors for p53 protein level using the antibody PAB1801. Nine (23%) of 39 sweat gland carcinomas were positive for p53 protein. Among these carcinomas, six of 12 cases of extramammary Paget's disease were positive using immunohistochemistry. No other correlation between tumor subtype and p53 reactivity was detected. Among 43 benign sweat gland tumors, only one case displayed staining for p53. We conclude that p53 protein plays a role in a subset of sweat gland tumors, especially in extramammary Paget's disease.

Coexpression of cytokeratin and vimentin intermediate filaments in benign and malignant sweat gland tumors.

The coexpression of cytokeratin and vimentin intermediate filaments has been immunohistochemically evaluated in 124 benign and malignant sweat gland tumors of various types in comparison to normal sweat glands. In addition, all neoplasms have been stained by an antibody to alpha-smooth muscle actin. Epithelial cells reacted with the pan-cytokeratin antibody lu-5. In normal sweat glands, vimentin immunoreactivity was restricted to myoepithelial cells and to some cells of the coiled duct. In benign sweat gland tumors (n = 88), coexpression of vimentin and alpha-smooth muscle actin was frequently found in basal cells of neoplasms considered to differentiate towards the secretory coil of the eccrine or apocrine gland. These included eccrine spiradenoma, apocrine cystadenoma, hidradenoma papilliferum, syringocystadenoma papilliferum, and cylindroma. Thus, in these tumors, vimentin-reactive cells corresponded to myoepithelial cells. Vimentin-positive cells were also found in 14 of 36 sweat gland carcinomas, including 1 case of sclerosing sweat duct carcinoma, 1 case of porocarcinoma, 4 cases of eccrine adenocarcinoma, 1 case of mucinous eccrine carcinoma, and 5 cases of apocrine adenocarcinoma. Co-expression of vimentin and alpha-smooth muscle actin was observed in some cells of eccrine and apocrine adenocarcinomas. Therefore, in these neoplasms, some vimentin-positive cells appear to represent myoepithelial cells. In contrast, vimentin-positive cells in all other malignant tumors did not express alpha-smooth muscle actin. Our results indicate that coexpression of cytokeratin and vimentin may be frequently found in a variety of benign and malignant sweat gland tumors. In the majority of these neoplasms, vimentin-positive cells correspond to myoepithelial cells. Because vimentin is not specific for myoepithelial cells, additional stains for alpha-smooth muscle actin should be performed to prove the myoepithelial nature of vimentin-positive cells.

Expression patterns of loricrin in various species and tissues.

In this study we analyzed the expression patterns of loricrin in various species and tissues using immunohistochemistry, immunoblotting and Northern blots. Loricrin is a glycine-, serine- and cysteine-rich protein expressed very late in epidermal differentiation in the granular layers of normal mouse and human epidermis. Later on in differentiation, loricrin becomes crosslinked as a major component into the cornified cell envelope by the formation of N epsilon-(gamma-glutamyl)lysine isopeptide bonds. This process either occurs directly or by the intermediate accumulation in L-keratohyaline granules of mouse epidermis and human acrosyringia. Loricrin was identified in all mammalian species analyzed by virtue of its highly conserved carboxy-terminal sequences revealing an electric mobility of approximately 60 kDa in rodents, rabbit and cow and of approximately 35 kDa in lamb and human on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Loricrin is expressed in the granular layer of all mammalian orthokeratinizing epithelia tested including oral, esophageal and fore-stomach mucosa of rodents, tracheal squamous metaplasia of vitamin A deficient hamster and estrogen induced squamous vaginal epithelium of ovary ectomized rats. Loricrin is also expressed in a few parakeratinizing epithelia such as BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine]-induced murine bladder carcinoma and a restricted subset of oral and single vaginal epithelial cells in higher mammals. Our results provide further evidence that the program of squamous differentiation in internal epithelia of the upper alimentary tract in rodents and higher mammals differ remarkably. In addition, we also have noted the distinct distribution patterns of human loricrin and involucrin, another major precursor protein of the cornified cell envelope.

Cloning and sequencing of two Candida parapsilosis genes encoding acid proteases.

Candida parapsilosis secretes an inducible acid protease (ACP) when cultivated in the presence of bovine serum albumin as the sole nitrogen source. In order to clone the ACP gene (ACP) of C. parapsilosis, a genomic library was screened with C. tropicalis ACP as the probe. Two different ORFs, ACPR and ACPL, were found to hybridize with the C. tropicalis ACP. ACPR contained a DNA sequence in agreement with the N-terminal amino acid sequence of C. parapsilosis ACP isolated from culture supernatants. ACPR was shown to be expressed and functional in a C. tropicalis acid protease mutant (acp) and with SDS-PAGE the protein product showed the same mobility as the ACP secreted by C. parapsilosis. These results imply that ACPR encodes the C. parapsilosis ACP. The deduced amino acid sequence of ACPR is similar to the amino acid sequence of proteases of the pepsin family. As in the case of the C. tropicalis and C. albicans ACP, the 5' extremity of ACPR revealed a propeptide containing two Lys-Arg amino acid pairs that have been identified as peptidase processing sites in several yeast-secreted peptides and protein precursors. As judged from the deduced amino acid sequences, the ACPL product would be similar to that of ACPR; however, a protein corresponding to ACPL was not found in supernatants from C. parapsilosis liquid cultures. In addition, ACPL did not complement the C. tropicalis acp mutant. We conclude that ACPL is a pseudogene or serves an as yet unidentified function.

[Eccrine syringofibroadenoma. Report of clinical aspects and histology of two cases with review of the literature]. / Das ekkrine Syringofibroadenom. Bericht über Klinik und Histologie zweier Fälle mit Literaturübersicht.

Eccrine syringofibroadenoma is a rare benign neoplasm with differentiation towards eccrine ducts. Its recognition depends on the histopathological examination; it is to be differentiated mainly from fibroepithelial basal cell carcinoma. Two new cases which occurred in a 70-year-old woman and a 39-year-old woman are presented. Clinically the two neoplasms were each a solitary hyperkeratotic, partially oozing nodule. On microscopic examination they both showed proliferation of small neoplastic cells in a reticular pattern; immature or mature eccrine ductal structures were seen within them. The neoplastic cells in the two cases differed in their content of PAS-positive glycogen.

Disruption of the gene encoding the secreted acid protease (ACP) in the yeast Candida tropicalis.

The gene for the secreted acid protease (ACP), a potential virulence factor of Candida species, was inactivated in Candida tropicalis by gene disruption. The disruption was performed by cotransformation of an ade2 C. tropicalis mutant with a linear DNA fragment carrying a deletion in ACP, and the replicative vector pMK16 which carries a selectable ADE2 gene marker. Few of the transformants exhibited lower protease secretion levels and were shown to have one deleted and one unaffected ACP copy, since C. tropicalis is a diploid yeast. These transformants were rendered homozygotic for this deletion by mild UV-treatment. One of the homozygotic acp deletion mutants obtained was completely devoid of extracellular protease activity and grew poorly on bovine serum albumin-containing medium. This mutant could be complemented by an ACP fragment inserted in pMK16, but also by an acid protease gene isolated from C. parapsilosis.

[Naevus follicularis keratosus: clinical aspects, histology and histogenesis]. / Naevus follicularis keratosus: Klinik, Histologie und Histogenese.

The clinical, histological and histogenetic aspects of naevus follicularis keratosus (NFK) ("naevus comedonicus") are reported. Clinically, NFK appears mostly as linear and unilateral groups of dark comedo-like plugs. Clinical forms include variants with minimal and distinctive deviations from the basic form. Recurrent inflammation is not mandatory. Histological examination reveals keratin-filled infundibula, with granular layers that are always present but though not always equally obvious. This finding corresponds to the mode of keratinization in the follicular infundibulum. Overall, the findings are indicative of a harmartoma of the follicular infundibulum with additional rudimentary sebaceous glands.