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Biomedical subjects

R Happle

Publications and source records attributed to R Happle.

At least 55 records · Page 3Linked to original sources
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↗
PubMed2000

[Alternative medicine: really an alternative to academic medicine?].

Numerous courses on alternative medicine are regularly advertised in Deutsches Arzteblatt, the organ of the German Medical Association. The present German legislation likewise supports this form of medicine, and this explains why Iscador, an extract of the mistletoe, is found in the Rote Liste, a directory of commercially available medical drugs, under the heading "cytostatic and antimetastatic drugs" although such beneficial effect is unproven. To give another example, a German health insurance fund was sentenced to pay for acupuncture as a treatment for hepatic failure. This judgement is characteristic of the present German judicial system and represents a victory of "oracling irrationalism" (Popper). The astonishing popularity of alternative medicine can be explained by a revival of romanticism. An intellectually fair opposite position has been delineated by Karl Popper in the form of critical rationalism. It is important to realize, however, that our decision to adhere to rational thinking is made in the innermost depth of our heart but not on the basis of rational arguing. Rather, the decision in favor of reason has a moral dimension.

Complementary Therapies↗
PubMed2000

[Lichen striatus or Blaschkitis in the adults. Variations of the same entity?].

A 64-year-old woman presented with extensive erythematous papulosquamous lesions along the lines of Blaschko on the right half of the trunk and the right leg. The clinical and histological features led to the diagnosis of lichen striatus, a dermatosis which usually appears during childhood. Treatment with acitretin led to marked improvement. Lichen striatus and its differential diagnoses--particularly "blaschkitis of adulthood" as first described in 1990--are discussed.

Biopsy↗
PubMed2000

[Mapping and molecular analysis of hereditary skin diseases. The status of current research].

The revolutionary advances of molecular genetics have made it possible in recent years to map the genes and identify the gene products of numerous hereditary skin diseases. The number of newly recognized gene loci responsible for genodermatoses is increasing almost every week. In this review, the gene locations of approximately 200 genodermatoses, categorized into various nosological groups, are presented and their genes or gene products, if already known, are documented in a tabular form. In this way novel, etiologically oriented criteria of classification emerge. On the one hand, dissimilar phenotypes can be attributed to one single gene locus, and on the other hand some clinically uniform genodermatoses have to be assigned to a number of different gene loci. Moreover, this review shows for which phenotypes additional research is particularly needed because we know the gene loci but so far not the underlying genes or gene products.

Chromosome Mapping↗
PubMed2000

Linear verrucous hemangioma.

A 16-year-old male patient had multiple angiokeratotic lesions arranged in a linear pattern on his left arm. Histopathologic examination showed characteristic features of verrucous hemangioma. This entity should be distinguished from angiokeratoma or simple hemangioma. The linear arrangement of lesions as observed in this case may reflect genetic mosaicism. Deep surgery is the best treatment for verrucous hemangioma.

Adolescent↗
PubMed2000

Treatment with an anti-CD44v10-specific antibody inhibits the onset of alopecia areata in C3H/HeJ mice.

A murine CD44v10-neutralizing antibody has been reported to impair delayed-type hypersensitivity reactions. Because alopecia areata is characterized by a delayed-type hypersensitivity-like T cell mediated immune response, we addressed the question whether an anti-CD44v10-antibody influences the onset of alopecia areata. Therefore, we used the C3H/HeJ mouse model with the induction of alopecia areata in unaffected mice by the grafting of lesional alopecia areata mouse skin. Six grafted mice were injected (intraperitoneally) with anti-CD44v10, six grafted mice with anti-CD44standard, and six with phosphate-buffered saline only. After 11 wk phosphate-buffered saline injected animals on average had developed alopecia areata on 36.8% of their body. The onset of hair loss was slightly delayed and its extent reduced to 17.2% of their body in anti-CD44standard-treated mice. By contrast, five of six anti-CD44v10-treated mice did not show any hair loss and one mouse developed alopecia areata on only 1% of the body. Immunohistochemical examination revealed a marked reduction of perifollicular CD8+ lymphocytes and, to a lesser degree, CD4+ cells as well as a decreased expression of major histocompatibility complex class I on hair follicle epithelium in anti-CD44v10-treated mice as compared with phosphate-buffered saline or anti-CD44 standard-treated mice. Our data show that anti-CD44v10 is able to inhibit the onset of alopecia areata in C3H/HeJ mice. This might be accomplished by an anti-CD44v10-triggered impairment of immune cell homing (e.g., CD8+ T cells), resulting in a decrease of their number in target tissues.

Alopecia Areata↗
PubMed2000

Molecular genetics of the hair follicle: the state of the art.

For those who are interested in the biology of skin and its derivatives, these are interesting times indeed. In a mere 5 years, the field has been revolutionized by the application of molecular genetics to human congenital skin disorders. Where dermatology first was limited to observation and empirics, there are now DNA-diagnostics, rational drug design, and perhaps even gene therapy available soon. In particular, the study of rare human syndromes involving abnormalities of hair growth and structure has yielded new insights into the regulation of cell growth and differentiation in the hair follicle. As this structure shows a cyclic pattern of differentiation, it may give new information concerning the regulation of cell differentiation in general. This review covers the recent developments in this fast-moving field. First, we will give a short introduction to (structural) hair biology. Next, we will try to fit these data into the framework of what is already known and attempt to present a unified model for hair follicle growth and differentiation.

Animals↗