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R Happle

Publications and source records attributed to R Happle.

At least 37 records · Page 2Linked to original sources
PubMed2002

17alpha-estradiol induces aromatase activity in intact human anagen hair follicles ex vivo.

For topical treatment of androgenetic alopecia (AGA) in women, solutions containing either estradiol benzoate, estradiol valerate, 17beta- or 17alpha-estradiol are commercially available in Europe and some studies show an increased anagen and decreased telogen rate after treatment as compared with placebo. At present it is not precisely known how estrogens mediate their beneficial effect on AGA-affected hair follicles. We have shown recently that 17alpha-estradiol is able to diminish the amount of dihydrotestosterone (DHT) formed by human hair follicles after incubation with testosterone, while increasing the concentration of weaker steroids such as estrogens. Because aromatase is involved in the conversion of testosterone to estrogens and because there is some clinical evidence that aromatase activity may be involved in the pathogenesis of AGA, we addressed the question whether aromatase is expressed in human hair follicles and whether 17alpha-estradiol is able to modify the aromatase activity. Herewith we were able to demonstrate that intact, microdissected hair follicles from female donors express considerably more aromatase activity than hair follicles from male donors. Using immunohistochemistry, we detected the aromatase mainly in the epithelial parts of the hair follicle and not in the dermal papilla. Furthermore, we show that in comparison to the controls, we noticed in 17alpha-estradiol-incubated (1 nM) female hair follicles a concentration- and time-dependent increase of aromatase activity (at 24 h: 1 nM = +18%, 100 nM = +25%, 1 micro M = +57%; 24 h: 1 nM = +18%, 48 h: 1 nM = +25%). In conclusion, our ex vivo experiments suggest that under the influence of 17alpha-estradiol an increased conversion of testosterone to 17beta-estradiol and androstendione to estrone takes place, which might explain the beneficial effects of estrogen treatment of AGA.

Adult↗
PubMed2002

Differences of skin irritation between Japanese and European women.

BACKGROUND: After using cosmetics, Japanese women frequently complain about sensitive, stinging skin. We wondered whether Japanese women's skin is more sensitive than that of Caucasians. OBJECTIVES: To examine possible racial differences of skin irritation and subjective sensations. METHODS: We performed patch testing on the forearm with sodium lauryl sulphate (SLS) at different concentrations (0.25%, 0.5%) and 24-h exposure time. Skin reaction was evaluated by measurement of transepidermal water loss (TEWL), stratum corneum hydration, sebum secretion, laser Doppler flowmetry (LD), content of melanin and erythema. During a stinging test with 10% lactic acid (applied to one side of the cheeks) the subjects were asked to describe the present intensity of any sensation. We used a Chromameter to measure skin colour before and after application of lactic acid. This study was performed in Marburg, Germany, with healthy Japanese and German women living in Marburg. RESULTS: After SLS testing, we found no significant differences of the barrier function in the stratum corneum, but we found significant subjective sensory differences between Japanese and German women. CONCLUSIONS: Japanese women may complain about stronger sensations reflecting a different cultural behaviour rather than measurable differences in skin physiology; however, a faster penetration of SLS in Japanese cannot be excluded.

Adult↗
PubMed2002

Changes in skin physiology during bath PUVA therapy.

BACKGROUND: Frequent bathing leads to a skin barrier damage with various changes in physiological skin parameters. Conversely, ultraviolet (UV) irradiation may improve the impaired skin barrier by reducing inflammatory reactions. OBJECTIVES: The aim of this study was to investigate the changes of physiological skin parameters during a therapy with 8-methoxypsoralen (8-MOP) bathing and subsequent UVA irradiation. METHODS: Thirty patients with a skin disease without barrier disruption were treated with daily bathing in a 8-MOP solution (0.0005%) and subsequent UVA irradiation. Multiple physiological skin parameters (transepidermal water loss, skin blood flow, skin colour, sebum content, skin hydration) were measured repeatedly on clinically non-affected skin on the back, forearm and forehead. In addition, patch testing with sodium lauryl sulphate (SLS) (0.5%) was performed on the forearm and on the back. RESULTS: We found a moderate but significant disturbance of skin barrier and hydration on the forearm and the back (bathing + irradiation) after increasing dosages of therapy. In addition, SLS testing leads to stronger reactions. CONCLUSIONS: We conclude that on clinically healthy skin the impairment of skin barrier by frequent bathing cannot be completely compensated by subsequent UVA irradiation. When conducting a treatment with 8-MOP bathing and UVA irradiation a concomitant therapy supporting the recovery of skin barrier, e.g. with moisturizer, should be performed.

Adult↗
PubMed2002

HID and KID syndromes are associated with the same connexin 26 mutation.

BACKGROUND: Keratitis-ichthyosis-deafness (KID) syndrome is a debilitating ectodermal dysplasia that predisposes patients to develop squamous cell carcinomas in addition to leading to profound sensory deafness and erythrokeratoderma. We recently demonstrated that KID can be caused by a specific missense mutation in connexin 26 (GJB2). Another syndrome, called hystrix-like ichthyosis-deafnesss (HID) syndrome, strongly resembles the KID syndrome. These disorders are distinguished mainly on the basis of electron microscopic findings. We hypothesized that KID and HID syndromes may be genetically related. OBJECTIVE: To demonstrate by mutation analysis that HID and KID syndromes are genetically indistinguishable. METHODS: DNA was extracted from paraffin-embedded tissue samples of the first HID syndrome patient described in the literature. Since the KID syndrome mutation abolishes an AspI restriction site, we were able to screen the patient's DNA by polymerase chain reaction and subsequent restriction enzyme analysis. RESULTS: Restriction analysis of the connexin 26 gene in HID syndrome demonstrated the presence of the KID syndrome mutation that we previously described. This result was confirmed by direct DNA sequencing. CONCLUSIONS: We show that KID and HID syndromes are identical at the molecular level and confirm the clinical impression that these syndromes are one and the same. That previous clinical reports made a distinction may be a consequence of sampling artefacts; alternatively, genetic background effects such as the presence of concurrent mutations in other skin-expressed genes may modify the phenotype.

Connexin 26↗
PubMed2001

Phylloid pattern of pigmentary disturbance in a case of complex mosaicism.

Among the various types of pigmentary disturbances associated with mosaicism, the phylloid pattern (Greek phyllon = leaf, eidos = form) is characterized by multiple leaf-like patches reminiscent of an art nouveau painting. The number of cases displaying this unusual pattern is so far limited. We describe a phylloid pattern of hypomelanosis in a 3-year-old girl with multiple congenital anomalies including microcephaly, midfacial hypoplasia, cleft lip, coloboma, posteriorly rotated ears, pectus carinatum, and pronounced mental and physical retardation. In addition, this child had oval or oblong patches of hyperpigmentation involving the trunk in a horizontal arrangement dissimilar from the phylloid hypomelanotic pattern. In peripheral blood lymphocytes a karyotype 46,XX,-13,+t(13q;13q) was consistently found, whereas cultured skin fibroblasts showed a complex form of mosaicism comprising three different abnormal cell lines (46,XX,-13,+t(13q;13q)/45,XX,-13/45,XX,-13,+frag). This case provides further evidence that the phylloid pattern represents a separate category of pigmentary disturbance to be distinguished from other types of cutaneous mosaicism such as the lines of Blaschko or the checkerboard arrangement.

Abnormalities, Multiple↗
PubMed2001

[Phylloid hypomelanosis and mosaic trisomy 13: a new etiologically defined neurocutaneous syndrome].

The term phylloid hypomelanosis is proposed to denote a new etiologically defined neurocutaneous syndrome. The hallmark of this trait is a pattern of hypopigmentation consisting of round or oval lesions, large asymmetrical areas reminiscent of the leaves of a begonia, as well as pear-shaped areas or oblong macules. The term phylloid pattern is derived from Greek phyllon=leaf and eidos=form. In 5 out of 6 cases in which cytogenetic findings were reported, a mosaic trisomy 13 or translocation trisomy 13 was found. All patients showed CNS defects with mental retardation. In addition, absence of corpus callosum, conductive hearing loss, choroidal and retinal coloboma,cranio-facial defects as well as brachydactyly,clinodactyly, camptodactyly and other skeletal anomalies were reported. In contrast to hypomelanosis of Ito which is associated with many different forms of genetic mosaicism, phylloid hypomelanosis most likely represents a cytogenetically rather uniform neurocutaneous phenotype.

Adolescent↗
PubMed2001

[Prurigo pigmentosa].

Prurigo pigmentosa is rather frequently observed in Japan. By contrast, this skin disease has so far rarely been reported in German speaking countries or elsewhere in Europe. In order to make the European dermatologists familiar with this peculiar skin disease, the epidemiological features as well as the clinical and histopathological findings are reviewed. The disease can be discriminated from prurigo simplex subacuta by the typical reticular hyperpigmentation, by the sparing of arms and legs and by the response to treatment with dapsone or minocycline. Additional differential diagnostic possibilities include lichen amyloidosus and confluent and reticulate papillomatosis of Gougerot-Carteaud. Diabetes or malnutrition may represent etiological factors. Because this unusual skin disease may also occur in Europe, dermatologists here should include prurigo pigmentosa in the differential diagnosis of acquired pigmentary disorders.

Adolescent↗
PubMed2001

[Segmental type 2 manifestation of autosome dominant skin diseases. Development of a new formal genetic concept].

The prevailing theory says that mosaic forms of autosomal dominant skin diseases originate from postzygotic new mutations. This theory is no longer generally valid. According to a new rule of dichotomy, we can distinguish two types of segmental manifestations. The type 1 reflects heterozygosity for a postzygotic new mutation, whereas the type 2 results from loss of the corresponding wildtype allele occurring in a heterozygous embryo and reflects either homozygosity or hemizygosity for the underlying mutation, giving rise to rather pronounced segmental lesions that are superimposed on the ordinary nonsegmental phenotype. Autosomal dominant skin diseases exemplifying the concept of type 2 segmental manifestation so far include neurofibromatosis 1, tuberous sclerosis, cutaneous leiomyomatosis, glomangiomatosis, Buschke-Ollendorff syndrome, multiple syringomas, multiple trichoepitheliomas, multiple basaloid follicular hamartomas, multiple nevoid basal cell carcinomas, Darier disease, Hailey-Hailey disease, epidermolytic hyperkeratosis of Brocq, KID syndrome, disseminated superficial actinic porokeratosis and autosomal dominant dyskeratosis congenita. A strikingly high frequency of type 2 segmental involvement has been documented in cutaneous leiomyomatosis, glomangiomatosis and disseminated superficial actinic porokeratosis. It should be noted that there is so far no molecular proof for the proposed rule of dichotomy that has been developed from clinical dermatology. According to present knowledge, however, it is very likely that molecular analysis will confirm the described concept that can explain some so far enigmatic features as observed in autosomal dominant genodermatoses.

Alleles↗
PubMed2001

Which bioengineering assay is appropriate for irritant patch testing with sodium lauryl sulfate?

For testing with sodium lauryl sulphate (SLS), measurements of transepidermal water loss (TEWL) and cutaneous blood flow with laser Doppler (LD) are considered to be the most reliable methods. The aim of this study was to determine which method of measurement should be preferred when conducting SLS testing under varying conditions. Patch testing with SLS at different concentrations and exposure times was performed. TEWL values were compared with those of LD. TEWL values showed distinct changes at low SLS concentrations and short application periods. By contrast, higher SLS concentrations were necessary to increase LD values. Short application of patches changed TEWL rather than LD values. When evaluating SLS patch testing by bioengineering methods, TEWL measurement appears to be more suitable for a test procedure that provokes mild skin reactions (SLS concentration <1%), whereas LD measurement is more appropriate to evaluate pronounced skin reactions (SLS concentration >or=1%).

Dermatitis, Irritant↗
PubMed2001

The feasibility of quantitative analysis of androgen metabolism by use of single dermal papillae from human hair follicles.

Androgenetic alopecia (AGA) is a dihydrotestosterone-mediated process, characterized by continuous miniaturization of androgen sensitive hair follicles (HF). Although increased 5 alpha-reductase (5aR) activity in affected HF is a key feature in the pathogenesis of AGA, only little is known about the in vivo expression of 5aR within AGA-affected HF. Recent studies have shown that the dermal papilla (DP) is the predominant site of type 2 5aR expression within the human HF, but direct measurements of 5aR activity in intact DP of AGA-affected HF have not been reported so far, mainly because of technical problems. Hence there is a need for a reliable and sensitive method of measuring 5aR activity in fresh tissues. As a novel approach, we used freshly isolated, intact DP and a highly sensitive HPLC-radiomatic flow scintillation system to measure 5aR. In this way we were able to measure 5aR even in small DPs from miniaturized HF. Our results show that DP from the occipital scalp express ex vivo considerable amounts of 5aR activity, but the measurable enzyme activities of individual DP differ considerably. Therefore the use of only one or two DP is at present not a reliable tool to analyze 5aR activity ex vivo.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2001

Irritant patch testing with sodium lauryl sulphate: interrelation between concentration and exposure time.

BACKGROUND: It is well known that the degree of skin reaction to an irritant depends on its concentration and exposure time. OBJECTIVES: To determine the interrelationship between the concentration of sodium lauryl sulphate (SLS) and exposure time in both weak (subclinical) and severe reactions. METHODS: Patch testing with SLS was performed at different concentrations (0.125%, 0.25%, 0.5%, 1.0% and 2.0%) and with different exposure times (3, 6, 12, 24 and 48 h). Evaluation was conducted by measurement of transepidermal water loss and by laser-Doppler flowmetry both 30 min and 24 h after patch removal. RESULTS: We found more reliable and constant skin reactions 24 h after patch removal, and a higher correlation between SLS concentration and skin reaction. CONCLUSIONS: We conclude that the concentration of SLS influences the test outcome to a larger degree than the exposure time. We present formulae by which the outcome of SLS patch testing at various SLS concentrations ranging from 0.125% to 2% and any exposure time between 3 and 24 h can be estimated.

Adolescent↗
PubMed2001

Murine auricular transepidermal water loss -- a novel approach for evaluating irritant skin reaction in mice.

UNLABELLED: The standard method for evaluating contact allergy in mice is the ear swelling technique. However, in experimental irritant contact dermatitis, the epidermal barrier disruption, that represents a predominant effect of irritants, cannot be assayed by this METHOD: An appropriate method to evaluate barrier disruption is the measurement of transepidermal water loss (TEWL) but to date this has so far been possible only on the trunk of hairless or shaved mice. We therefore developed a new technique to measure the TEWL of mice ears (murine auricular TEWL: MATEWL). After patch testing with irritants and allergens, respectively, we found that the ear swelling method is most suitable for evaluating allergic skin reactions, whereas MATEWL is most appropriate for evaluating irritant skin reactions.

Animals↗
PubMed2001

The lines of Blaschko on the head and neck.

BACKGROUND: The system of Blaschko's lines has been insufficiently documented on the head and neck. OBJECTIVE: The aim of the study was to elaborate this pattern in a comprehensive way. METHOD: One hundred eighty-six figures showing skin lesions following Blaschko's lines on the head and neck were collected from literature and patient files, transposed into drawings, and subsequently categorized according to 3 standard perspectives. Transparent sheets were superimposed to delineate an archetypical pattern. RESULTS: The definite lines are presented in a frontal, lateral, and dorsal view. On the face they show an hourglass-like configuration converging on the nasal root. However, in several areas these lines intersect at an angle of almost 90 degrees. On the scalp they form a spiral configuration. CONCLUSION: The system of Blaschko's lines on the head and neck as elaborated by this study is more precise than previously published diagrams. Remarkably, this archetypical pattern shows definite crossing of lines.

Facial Dermatoses↗
PubMed2001

Cutaneous leiomyomatosis with type 2 segmental involvement.

A 21-year-old man had histologically-confirmed diffuse cutaneous leiomyomatosis. The lesions showed a peculiar distribution in that they predominantly involved several segments of the right side of his body; in addition, less extensive, nonsegmental lesions were present on both sides of the body. Although this case was apparently sporadic, the genetic mechanism of loss of heterozygosity provides a plausible explanation for this unusual presentation. If the patient were heterozygous for the underlying mutation, at an early developmental stage a postzygotic event of loss of heterozygosity would have given rise to a type 2 segmental involvement, resulting in pronounced lesions superimposed on the disseminated tumors of the ordinary phenotype.

Adult↗