Search PubMed⌕ Search

Biomedical subjects

R Happle

Publications and source records attributed to R Happle.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2001

Didymosis aplasticosebacea: coexistence of aplasia cutis congenita and nevus sebaceus may be explained as a twin spot phenomenon.

BACKGROUND: Co-occurrence of aplasia cutis congenita and nevus sebaceus has sometimes been observed. OBJECTIVE: We propose a genetic mechanism that may explain this coexistence of two different congenital skin disorders. METHODS AND RESULTS: We review 15 cases as reported in the literature and present an additional case. To explain the temporal and spatial proximity of the two skin lesions we advance the concept of twin spotting for which we propose the term didymosis (Greek didymos = twin). In an embryo heterozygous for two different recessive mutations localized on either of a pair of homologous chromosomes, an event of somatic recombination would occur at an early developmental stage, giving rise to two different cell clones homozygous for either mutation. CONCLUSION: The concept of didymosis aplasticosebacea is so far hypothetical. Future molecular research may show whether this concept holds true.

Child↗
PubMed2001

Paradominant inheritance may explain familial occurrence of Cutis marmorata telangiectatica congenita.

Cutis marmorata telangiectatica congenita (CMTC) is a rare congenital vascular anomaly that virtually always occurs sporadically and in a patchy, quadrant, unilateral or otherwise segmental manifestation. This would suggest mosaicism of a postzygotic mutation. Some authors, however, described CMTC occurring in several members of a family. This paradox may be explained by the concept of paradominant inheritance. Heterozygous individuals carrying a 'paradominant' mutation are, as a rule, phenotypically normal. The mutation can therefore be transmitted unperceived through many generations. The trait only becomes manifest when a postzygotic mutation occurring during early embryogenesis gives rise to loss of heterozygosity and forms a mosaic population of cells being either homozygous or hemizygous for the mutation. This concept may explain the occasional familial occurrence of CMTC.

Child, Preschool↗
PubMed2001

Current and potential agents for the treatment of alopecia areata.

Alopecia areata is considered to be a T-cell mediated autoimmune disease of the hair follicle. Current immunosuppressive approaches and immunomodulatory treatment with contact sensitizers such as diphenylcyclopropenone and squaric acid dibutylester are dealt with in this review article. The efficacy of the various modes of treatment is evaluated by a review of literature and their mode of action is discussed. In accordance with the mechanism of autoimmune pathogenesis of AA, improved future treatments may be immunosuppressive or immunomodulatory, or they should otherwise protect the hair follicle from the injurious effects of the inflammation. Such possible future therapeutic approaches include the use of liposomes as an improved vehicle, application of immunosuppressive cytokines like TGF-beta and IL-10, inhibition of apoptosis mediated by the Fas-FasL system, inhibition of the lymphocyte homing receptor CD44v10, induction of tolerance as well as principles of gene therapy.

Adjuvants, Immunologic↗
PubMed2000

Nonsyndromic type of hereditary multiple basal cell carcinoma.

An autosomal dominant phenotype characterized by multiple superficial basal cell carcinomas (BCC) without associated anomalies is postulated on the ground of the following data. There are several reports on multiple BCC occurring in two generations of a family, including male-to-male transmission. There are also three reports of a strictly unilateral manifestation of multiple superficial BCC, suggesting mosaicism. The father of one of the patients with unilateral involvement was affected with multiple disseminated BCC, which suggests a type 2 segmental manifestation in the son, reflecting loss of heterozygosity that occurred at an early stage of embryogenesis. The three cases of unilateral arrangement would be difficult to explain without the assumption that multiple nonsyndromic superficial BCC may occur as a distinct mendelian trait.

Adult↗
PubMed2000

Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome.

We report for the first time that CHILD syndrome (MIM 308050), an X-linked dominant, male-lethal trait characterized by an inflammatory nevus with striking lateralization and strict midline demarcation, as well as ipsilateral hypoplasia of the body is caused by mutations in the gene NSDHL located at Xq28 (NAD(P)H steroid dehydrogenase-like protein) encoding a 3beta-hydroxysteroid dehydrogenase functioning in the cholesterol biosynthetic pathway. SSCA and genomic sequence analysis of NSDHL identified in 6 patients with CHILD syndrome, including one boy as well as a mother and her daughter, mutations potentially impairing protein function. This phenotype is distinct from, but shares various clinical and biochemical findings with chondrodysplasia punctata (CDPX2, MIM 302960). CDPX2 is due to mutations affecting a delta8-delta7 sterol isomerase (EBP, emopamil binding protein, at Xp11.22-p11.23) that functions downstream of NSDHL in a later step of cholesterol biosynthesis. EBP was unaffected in the patients analyzed by us demonstrating that CHILD syndrome and CDPX2 are not caused by allelic mutations. Two mouse X-linked dominant male-lethal traits, bare patches (Bpa) and striated (Str) had previously been associated with mutations in Nsdhl. They provide animal models for the study of CHILD syndrome, a further human condition due to mutations in a gene of the cholesterol synthesis pathway.

3-Hydroxysteroid Dehydrogenases↗