Search PubMed⌕ Search

Biomedical subjects

R Happle

Publications and source records attributed to R Happle.

At least 127 records · Page 7Linked to original sources
PubMed1997

Cancer proneness of linear porokeratosis may be explained by allelic loss.

BACKGROUND: It is well known that porokeratosis, a genetically heterogeneous disorder characterized by the histopathological feature of the cornoid lamella, shows an increased proneness to develop carcinoma. On the other hand, a significant mechanism in the origin of many forms of cancer is loss of heterozygosity or allelic loss. OBJECTIVE: Because it has recently been proposed that linear porokeratosis may result from allelic loss, one might expect that linear porokeratosis is especially prone to malignant degeneration. In order to test this hypothesis, a review of case reports was performed. METHOD: Cases of cancer-associated porokeratosis were collected from the European language literature and assigned to one of 5 different types [plaque type of Mibelli (PM); disseminated actinic superficial porokeratosis (DSAP); porokeratosis palmaris, plantaris et disseminata (PPPD); porokeratosis punctata palmaris et plantaris (PPPP); linear porokeratosis (LP)]. RESULTS: Malignant or premalignant lesions were reported in 9 cases of PM, 15 cases of DSAP, 3 cases of PPPD, 1 case of PPPP and 21 cases of LP. CONCLUSION: This analysis supports the view that among the various forms of porokeratosis, the linear type is particularly susceptible to malignant degeneration. Arguments are presented in favor of the assumption that the genetic mechanism of allelic loss giving rise to LP may represent an initial step in the development of cancer.

Alleles↗
PubMed1997

Phacomatosis pigmentokeratotica: a patient with the rare melanocytic-epidermal twin nevus syndrome.

We describe a 10-year-old girl affected with a speckled lentiginous nevus and an epidermal nevus of the organoid type on corresponding parts of the body. On histopathological examination, the lesions showed epidermal hyperpigmentation and melanocytic hyperplasia on the one hand and verrucous epidermal acanthosis with sebaceous hyperplasia on the other hand. Except for a minor deviation of the spine, the patient had no obvious extracutaneous symptoms. Happle et al. have recently interpreted the rare co-occurrence of these two types of nevi in spatial proximity as an example of twin spotting in human skin and proposed the name 'phacomatosis pigmentokeratotica'. In most cases, additional skeletal or neurological anomalies are found. These are dissimilar from the extracutaneous symptoms of the sebaceous nevus syndrome, from which phacomatosis pigmentokeratotica should be distinguished. Molecular studies are needed to prove the concept of twin spotting and to reveal a link to the extracutaneous manifestations.

Child↗
PubMed1997

Phorbol-myristate-acetate, but not interleukin-1 beta or insulin-like growth factor-I, regulates protein kinase C isoenzymes in human dermal papilla cells.

The in vitro growth of human hair follicles is inhibited by interleukin (IL)-1 beta and phorbol esters, such as phorbol-myristate-acetate (PMA), but enhanced by insulin-like growth factor (IGF)-I. Although this process is only incompletely understood, the dermal papilla as a pivotal part of the hair follicle is almost certainly involved. Since protein kinase C (PKC) isoenzymes are activated by phorbol esters and are key enzymes in signalling pathways of several hormones, neurotransmitters, and growth factors, we addressed the question whether the action of the above-mentioned hair growth-modulating substances may affect PKC isoenzymes in cultured dermal papilla cells (DPC). By Western blot analysis, protein kinase C alpha, -epsilon, -gamma, -iota, -lambda, and the RACK1 receptor protein were detected in dermal papilla cell cultures, whereas the isoenzymes delta and mu were expressed only at low levels and protein kinase C-beta, -theta, and -zeta, were not present. After PMA stimulation, the PKC alpha, -epsilon, and -gamma were translocated from the cytosol to the membrane fraction and subsequently down-regulated. PKC iota was down-regulated but not translocated, and PKC lambda and RACK1 were not affected by PMA. Neither, IL-1 beta nor IGF had an effect on PKC or RACK1 expression. We conclude that cultured DPC express a distinct PKC isoenzyme pattern and that the PMA-induced growth arrest in cultivated hair follicles may be transmitted via protein kinases, whereas the effects of IL-1 beta or IGF may be transduced via other signal transduction pathways or other cell types.

Blotting, Western↗
PubMed1997

Patchy dermal hypoplasia as a characteristic feature of Proteus syndrome.

BACKGROUND: The diagnostic criteria of Proteus syndrome include various lesions of localized overgrowth such as digital gigantism, hemihyperplasia with unilateral macrocephaly, epidermal nevus, and mesodermal hamartomas such as lipoma, lymphangioma, hemangioma, or fibroma. Hyperplasia of the plantar dermal tissue may result in a characteristic cerebriform appearance. However, hypoplastic lesions involving various tissues such as subcutaneous fat or muscles also may be observed in this syndrome. This paradoxical phenomenon has so far been underestimated, and the presence of circumscribed lesions of dermal hypoplasia has been entirely ignored. OBSERVATIONS: We report 4 cases of Proteus syndrome associated with large patches of dermal hypoplasia, resulting in a more prominent appearance of venous vasculature. CONCLUSIONS: Patchy dermal hypoplasia appears to be a characteristic feature within the spectrum of Proteus syndrome. The anomaly should not be confused with partial lipohypoplasia that may likewise be associated with this multisystem birth defect. From a review of the literature, we conclude that patchy dermal hypoplasia may have occurred in several previous cases. In the future, recognition of this cutaneous anomaly may help to establish the diagnosis in otherwise doubtful cases. To explain the coexistence of lesions of dermal hyperplasia and hypoplasia, we propose the genetic concept of "twin spotting." At the gene locus of Proteus syndrome the embryo would carry 1 allele giving rise to dermal overgrowth, whereas the corresponding allele would be responsible for a diminished proliferation of cutaneous fibroblasts. Somatic recombination may result in 2 different populations of cells homozygous for either allele.

Child↗
PubMed1997

In vivo formation of prostaglandin E1 and prostaglandin E2 in atopic dermatitis.

Immunological and biochemical alterations in atopic dermatitis have been attributed to a deficient conversion of omega-6 fatty acids (i.e. linoleic acid, gamma-linolenic acid, and dihomo-gamma-linolenic acid) to prostaglandin (PG) E1. In patients with atopic dermatitis, however, the formation of PGE1 has not been evaluated so far. We therefore measured plasma concentrations of 15-keto-13,14-dihydro-PGE1, which reflects endogenous PGE1 release, by gas chromatography-mass spectrometry in 31 patients with atopic dermatitis (aged 18-41 years, median 26 years) and in 31 healthy, age- and sex-matched control subjects. In order to exclude a metabolic shift from PGE1 to PGE2, we also measured the plasma levels of 15-keto-13,14-dihydro-PGE2. There was no difference between patients and control subjects with respect to plasma concentrations of 15-keto-13,14-dihydro-PGE1 (3.9-49.6, median 10.3 pg/ml vs. 3.2-80.4, median 8.3 pg/ml, P = 0.22), 15-keto-13,14-dihydro-PGE2 (11.6-201.0, median 24.8 pg/ml vs. 8.6-201.0, median 19.6 pg/ml, P = 0.10), and the ratio of 15-keto-13,14-dihydro-PGE1 to 15-keto-13,14-dihydro-PGE2 (0.17-1.39, median 0.41 vs. 0.2-1.17, median 0.45, P = 0.29). These results indicate that the endogenous formation of both PGE1 and PGE2 is normal in our patients. The results do not confirm the pivotal role that other authors have attributed to a deficient PGE1 formation in the pathogenesis of atopic dermatitis.

Adolescent↗
PubMed1997

Superciliary upsweep or tented eyebrows. A distinct mendelian trait.

Facial appearance is influenced by the anatomic relationship of the eyebrows and eyelids. Anatomic variants may characterize members of a pedigree and thus constitute a family mark. We studied three white families with circumscribed upward slanting eyebrows. In one pedigree the family mark was inherited over four generations, suggesting an autosomal dominant inheritance. In the other two families the eyebrow variation was documented in three members over two generations, compatible with an autosomal dominant mode of transmission. In two families the expression of the trait varied in the form of both bilateral and unilateral involvement. No diseases or malformations were associated with this eyebrow anomaly.

Eyebrows↗
PubMed1997

A rule concerning the segmental manifestation of autosomal dominant skin disorders. Review of clinical examples providing evidence for dichotomous types of severity.

It is well known that autosomal dominant skin disorders may sometimes become manifest in a mosaic form, involving the body in a linear, patchy, or otherwise circumscribed arrangement. Such cases can be explained by an early postzygotic mutation. The segmental lesions usually show the same degree of severity as that found in the corresponding nonmosaic trait. Occasionally, however, the intensity of involvement observed in the circumscribed area is far more pronounced. This phenomenon can be explained by delineating a rule of dichotomous segmental manifestations reflecting different states of zygosity. Heterozygosity for the mutation results in severity corresponding to that in the nonsegmental phenotype; loss of heterozygosity for the same allele causes markedly more severe involvement.

Chromosome Aberrations↗
PubMed1996

CHILD syndrome in a boy.

CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects) occurs, as a rule, exclusively in girls because the underlying X-linked gene exerts a lethal effect on male embryos. In this report the characteristic manifestations of CHILD syndrome are described in a 2-year-old boy with a normal chromosome constitution 46,XY. This exceptional case is best explained by the assumption of an early somatic mutation and thus compatible with the concept of X-linked dominant male-lethal inheritance of this trait.

Child, Preschool↗
PubMed1996

Cytokines and growth factors influence hair growth in vitro. Possible implications for the pathogenesis and treatment of alopecia areata.

Factors that influence the growth of the anagen hair follicle or initiate the switch to a catagen growth pattern have so far not been definitely determined, but there is increasing evidence that cytokines and growth factors play an important role during these processes. Recently we detected an aberrant in situ expression pattern of cytokines of the Th1 type (IFN gamma, IL-2) plus IL-1 beta expression in untreated alopecia areata (AA), and a switch to high levels of IL-10 TGF-beta 1 expression after successful treatment with the contact allergen diphenylcyclopropenone (DCP). Hence the question arose as to whether cytokines are able to arrest hair growth and whether IL-10 or TGF beta 1 have the capacity to antagonize this process. Using whole-organ cultures of microdissected human hair follicles we studied the effect of a panel of cytokines and growth factors on hair growth and on the gross morphology of the hair follicles in vitro. IL-2, IL-10 and IFN-gamma had no effect in this regard, whereas TGF beta 1 partially inhibited hair growth and EGF, TNF alpha and IL-1 beta completely abrogated it. EGF and TNF alpha induced the formation of a club-like hair follicle, similar to catagen morphology of the hair bulb, whereas hair follicles grown in the presence of IL-1 beta or TGF beta 1 showed no particular morphological changes. We conclude that cytokines and growth factors are pivotal regulators of hair growth at least in vitro. IL-1 is suggested as playing an important role during the pathogenesis of AA. Possible mediators of therapeutic contact dermatitis (IL-10, TGF beta 1, TNF alpha, PGE2) are, at least in vitro, not able to antagonize the IL-1 beta-triggered hair growth inhibition. Therefore, we infer that these mediators rather "modulate' the immune response in AA.

Alopecia↗
PubMed1996

[Perifollicular fibroma of the skin and colonic polyps: Hornstein-Knickenberg syndrome].

The syndrome of perifollicular fibromas and colonic polyps was delineated 20 years ago by Hornstein and Knickenberg; it probably occurs more frequently than suggested by the literature. Multiple perifollicular fibromas were found in a mother and daughter. The mother also had colonic polyps. This dermo-intestinal syndrome varies in its clinical manifestations, but it is probably an autosomal dominant trait. We believe that the Horn-stein-Knickenberg syndrome and the Birt-Hogg-Dubé syndrome are identical. If perifollicular fibromas are observed and cannot be explained as postinflammatory sequelae of acne, the patient should be examined for colonic polyps as an appropriate from of cancer screening.

Adenomatous Polyposis Coli↗
PubMed1996

[The sodium lauryl sulfate test. A noninvasive functional evaluation of skin hypersensitivity].

The purpose of this study was to determine whether 24 hour patch testing with 0.5% sodium lauryl sulphate (SLS) could reliably predict skin susceptibility to an irritant when compared with the alkali resistance test (ART), a widely used method employing sodium hydroxide. After having given informed consent, 40 patients (age range from 20 to 60 years) with an active irritant contact dermatitis (ICD), 40 patients in whom ICD had cleared, as well as 40 healthy volunteers serving as controls were tested. The skin responses to SLS were assessed both visually and by measurement of transepidermal water loss (TEWL) as an indicator of stratum corneum integrity. SLS significantly increased the erythema scores and TEWL in patients with healed ICD, and the increase of TEWL was even more pronounced in patients with active ICD. By contrast, a decrease in alkali resistance was found in patients with active ICD only but not in patients with healed ICD. The data obtained indicate that the SLS test, unlike ART, may provide a non-invasive tool predicting a possible constitutional skin susceptibility or indicating a subclinically impaired epidermal barrier function. However, because of the relatively high interindividual variation, a cut-clear statement concerning the skin susceptibility cannot be made by this test. On the other hand, the ART seems only to be useful for following and documenting the healing period following ICD.

Adult↗
PubMed1996

Topical immunotherapy in alopecia areata. What, how, and why?

At present the induction and elicitation of an ACD with potent contact allergens such as DCP appear to be the most effective, but still not definitively curative, approach in treating extensive forms of AA. Experimental data suggest that cytokines and growth factors such as IL 1 beta are involved in the pathogenesis of AA as well as the therapeutic effect mediated by contact sensitizers. It seems reasonable to assume that factors inherent in the late phase of ACD modulate a T-cell mediated mechanism responsible for AA, thus inducing hair regrowth. Such counteracting activities are most likely mediated by proinflammatory cytokines such as TNF-alpha, IL-10, or TGF-beta 1. This hypothesis may oversimplify the underlying immunologic mechanisms, but the effectiveness of topical immunotherapy in AA would be compatible with this concept. This mode of treatment is, however, a rather rough approach and recurrences are possible. It is hoped that advances in basic science will eventually allow us to find a more specific mode of treatment.

Administration, Topical↗
PubMed1996

Palmar papillomatous lesions reminiscent of epidermal nevus in a case of focal dermal hypoplasia: a nosological consideration.

A 40-year-old woman with focal dermal hypoplasia had a palmar papillomatous lesion showing a linear arrangement and histopathological features compatible with a diagnosis of epidermal nevus. This unusual manifestation of focal dermal hypoplasia is difficult to categorize. Undoubtedly the lesion reflects functional X-chromosome mosaicism. Although the mechanism of lyonization may give rise to true epidermal nevi such as CHILD nevus, we prefer to classify the present skin lesion as a nevoid disorder and not as an epidermal nevus.

Adult↗