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Biomedical subjects

R Happle

Publications and source records attributed to R Happle.

At least 253 records · Page 14Linked to original sources
PubMed1989

[Gregor Mendel and dysplastic nevi].

In contrast to what has so far generally been believed, dysplastic nevi do not appear to be mendelizing, but rather due to polygenic inheritance. In order to explain this contrasting idea, the following six theses are presented: (1) All dysplastic nevi are inherited in the same manner. (2) Dysplastic nevi constitute a continuous trait. (3) A "dysplastic nevus syndrome" in the form of a monogenic autosomal dominant trait probably does not exist. (4) A nonhereditary dysplastic nevus syndrome does not exist. (5) The number of the underlying genes that, considered separately, do of course follow the rules of mendelian inheritance is so far unknown. (6) A search for a single underlying gene defect is probably hopeless.

Chromosome Mapping↗
PubMed1988

Recruitment of quiescent (G0) cells following epidermal injury is initiated by activation of the phosphoinositol cycle.

Under normal circumstances, the rate of production of new cells by the epidermis is rather low, but injury results in a burst of mitotic activity that continues until repair is complete. It is now recognized that most cells of the germinative population are in a resting (G0) state, and "postinjury cell renewal" is the consequence of G0 cells entering the mitotic cycle. The biochemical events triggering this process, however, are unknown. Here we show that phorbol myristate acetate (PMA) is able to induce G0 mobilization in the epidermis of the nude mouse. Further, we demonstrate that amiloride (an inhibitor of the membrane Na+-H+ pump), applied topically to human skin, abolishes almost completely the regenerative response after experimental injury. We suggest that activation of the phosphoinositol cycle may initiate recruitment of G0 cells in the epidermis.

Adult↗
PubMed1988

Epidermolytic palmoplantar keratoderma of Vörner: is it the most frequent type of hereditary palmoplantar keratoderma?

In a retrospective study, we reevaluated the biopsies that had been obtained, during the past 11 years, from 26 patients presenting with hereditary palmoplantar keratoderma (PPK). Twelve out of 26 biopsies disclosed the histological features of epidermolytic hyperkeratosis, consistent with the diagnosis of epidermolytic PPK of Vörner. A review of the histologically examined cases of the literature revealed a comparable predominance of this hereditary PPK. We conclude that, in contrast to the current opinion, epidermolytic PPK of Vörner represents the most frequent type of hereditary PPK.

Child, Preschool↗
PubMed1988

Intra-epidermal accumulation of polymorphonuclear leukocytes in persistent palmoplantar pustulosis during treatment with acitretin.

Six patients with persistent palmoplantar pustulosis were treated with acitretin, and the clinical response was compared with the effect on the intra-epidermal accumulation of polymorphonuclear PMN leukocytes. A prompt improvement of pustule formation and subsequently decreased scaling and erythema was seen in all patients. Following discontinuation of therapy, a relapse occurred within 2 weeks. With dosages of 45 or 55 mg/day, the clinical scores were only slightly better than with 25 or 35 mg/day. In patients using 25 mg acitretin a day, the leukotriene B4-induced intra-epidermal accumulation of polymorphonuclear leukocytes was not affected. However, a dosage of 35 mg/day resulted in a significant inhibition of PMN accumulation, dosages of 45 and 55 mg/day causing an even more pronounced inhibition of this process. Although the effect of different dosages of acitretin is not clearly expressed in the severity scores, the dose-dependent effect on PMN chemotaxis in vivo might be of relevance when combination therapies are considered, in order to achieve a complete clinical clearance.

Acitretin↗
PubMed1988

Acne of the fulminans type following testosterone therapy in three excessively tall boys.

Ulcerative acne was observed in three boys who underwent long-term treatment with high doses of testosterone for excessively tall stature. Even after withdrawal of testosterone therapy, this devastating type of acne still persisted for several months. After starting isotretinoin treatment, two cases progressed to full-blown acne fulminans with systemic manifestations. In these two cases, oral isotretinoin therapy induced multiple lesions of hyperproliferative granulation tissue resembling pyogenic granuloma. Topical steroid treatment proved to be beneficial for this adverse effect. Systemic corticosteroid treatment was administered in one case. High testosterone levels during puberty may be an important trigger mechanism of acne fulminans and may explain why this disease almost exclusively affects male adolescents.

Acne Vulgaris↗
PubMed1988

[Goltz-Gorlin syndrome without focal dermal hypoplasia].

An unusual type of pigmentary disturbance is described in a 24-year-old man. The skin lesions consisted of patchy hyperpigmentation and hypopigmentation intermingled with teleangiectasias. They were distributed in a nevoid pattern following the lines of Blaschko. The patient had, in addition, multiple skin-colored papules in the cranial area of the gluteal fold, a fovea coccygea, and mild clinodactyly of both hands. Histopathologically, the dermis was of normal thickness and herniation of subcutaneous adipose tissue was absent in all five biopsies. This phenotype can be best explained as a case of Goltz-Gorlin syndrome without focal dermal hypoplasia. If this holds true, focal dermal hypoplasia in terms of a reduced thickness of the dermis is no longer a prerequisite for the diagnosis of the Goltz-Gorlin syndrome.

Adult↗
PubMed1987

Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin.

A genetic concept is advanced to explain the origin of several sporadic syndromes characterized by a mosaic distribution of skin defects. It is postulated that these disorders are due to the action of a lethal gene surviving by mosaicism. The presence of the mutation in the zygote will lead to death of the embryo at an early stage of development. Cells bearing the mutation can survive only in a mosaic state, in close proximity with normal cells. The mosaic may arise either from a gametic half chromatid mutation or from an early somatic mutation. This concept of origin is proposed to apply to the Schimmelpenning-Feuerstein-Mims syndrome, the McCune-Albright syndrome, the Klippel-Trenaunay syndrome, the Sturge-Weber syndrome, and neurocutaneous melanosis. Moreover, this etiologic hypothesis may apply to two other birth defects that have recently been delineated, the Proteus syndrome (partial gigantism of hands or feet, hemihypertrophy, macrocephaly, linear papillomatous epidermal nevus, subcutaneous hemangiomas and lipomas, accelerated growth, and visceral anomalies), and the Delleman-Oorthuys syndrome (orbital cyst, porencephaly, periorbital appendages, and focal aplasia of the skin.

Abnormalities, Multiple↗
PubMed1987

Abnormal expression of class I and class II major histocompatibility antigens in alopecia areata: modulation by topical immunotherapy.

Fifty-eight scalp biopsies were immunohistologically investigated with monoclonal antibodies against HLA-ABC, HLA-DR, and T6 antigens. The following 3 groups were compared: control biopsies obtained from healthy volunteers (n = 5) or patients with unrelated scalp diseases (n = 6); biopsies from untreated alopecia areata (AA), obtained either from untreated patients (n = 19) or from the untreated side in patients receiving unilateral treatment with the contact allergen diphencyprone (DCP) (n = 13); biopsies obtained from the treated side in patients receiving unilateral treatment with DCP (n = 13). While HLA-ABC antigens were strongly expressed by epidermal keratinocytes and the infundibular epithelium of hair follicles in all biopsies, these antigens were either not detectable or only faintly expressed on the subinfundibular epithelium and the hair matrix in the control series. By contrast, 30 out of 32 biopsies from untreated AA showed expression of HLA-ABC antigens on hair matrix epithelium, and the subinfundibular epithelium was HLA-ABC-positive in 15 out of 32 cases. In the biopsies from treated AA, HLA-ABC antigens were expressed on hair matrix epithelium in 9 out of 13 cases, and on the subinfundibular epithelium in 1 case. In the controls and untreated AA, HLA-DR expression was confined to dendritic cells in the epidermis and the follicular infundibulum. Its expression on hair matrix epithelium was found in 15 out of 32 biopsies from untreated AA and in 4 out of 13 biopsies from treated AA. In the control series, intrabulbar T6+ dendritic cells were either absent or present in low numbers. High numbers of intrabulbar T6+ cells were present in 7 out of 32 biopsies from untreated AA and in 0 out of 13 biopsies from treated AA. The data show that abnormal expression of class I major histocompatibility (MHC) antigens on hair matrix epithelium is a constant feature in AA, whereas class II MHC antigens are less frequently expressed. Topical immunotherapy with DCP, which induced expression of HLA-DR in epidermal keratinocytes in 6 out of 13 cases, reduced the abnormal expression of both HLA-ABC and -DR antigens in the epithelium of lower hair follicles in AA.

Alopecia Areata↗
PubMed1987

Multiple agminate Spitz naevi: review of the literature and report of a case with distinctive immunohistological features.

We describe a 13-year-old girl with multiple pigmented nodules and plaques arranged in a cluster in the right lumbar region, which had developed since infancy. Eleven of 15 lesions which were examined histologically were found to be Spitz naevi. The remaining four lesions were compound naevocellular naevi, and two of them showed focal dysplasia. Eight Spitz naevi were investigated immunohistologically with monoclonal antibodies against HLA-antigens and malignancy-associated melanocytic antigens which are rarely present in common naevi. Naevus cells in all lesions expressed HLA-ABC antigens, but lacked HLA-DR antigens in seven of the eight lesions. All naevi were positive for 'constitutive' (KG-6-56) and 'early' (K-1-2) markers of naevomelanocytic cells. In five of the eight Spitz naevi, at least one of the three malignancy-associated melanocytic antigens PAL-M1, A-1-43 and A-10-33 was found. The expression of malignancy-associated antigens in multiple agminate Spitz naevi is at variance with their benign clinical course.

Adolescent↗
PubMed1987

Retinoids in disorders of keratinization: their use in adults.

Hereditary disorders of keratinization may be a considerable handicap. Oral treatment with retinoids has been shown to be effective in many of these diseases. In the group of ichthyoses, the best results can be obtained in the various types of nonbullous congenital ichthyosis (erythrodermic autosomal recessive lamellar ichthyosis, nonerythrodermic autosomal recessive lamellar ichthyosis, autosomal dominant lamellar ichthyosis). It should be borne in mind, however, that retinoid therapy alone cannot lead to a complete response of these forms of ichthyosis and that this treatment cannot replace an appropriate topical treatment. During continuous treatment with etretinate a reduction of the dosis to 0.5 mg/kg is often necessary. Etretinate treatment of bullous congenital ichthyosiform erythroderma is more difficult, and it is advisable to begin with a low dosis of 0.25-0.5 mg/kg. The epidermolytic form of palmoplantar keratoderma is in our opinion no indication for retinoid treatment which seems to result inevitably in large erosions. Good or excellent results have been seen in other forms of palmoplantar keratoderma including mal de Meleda, Papillon-Lefèvre syndrome, erythrokeratodermia variabilis, verrucous epidermal nevi, Darier disease and pityriasis rubra pilaris. In patients with Darier disease it is wise to begin with a relatively low dosage of 0.5 mg/kg and to adjust the dosage to the further course of the disease. The same is true for the ichthyosis seen in the Netherton syndrome, which may be either a diffuse hyperkeratosis or ichthyosis linearis circumflexa. In view of the fact that any inherited keratinization disorder requires long-term treatment, the risk of bone toxicity should be carefully weighed against the benefit of this therapy. The results so far obtained indicate that the effect of etretin is comparable to that of etretinate in the treatment of inherited keratinization disorders. Intermittent therapy should be tried whenever possible. A combination therapy seems reasonable in pityriasis rubra pilaris of the adult type. We have seen good results by combination with PUVA treatment. Autosomal dominant ichthyosis vulgaris and X-linked recessive ichthyosis are inappropriate to treat with oral retinoid therapy because these diseases are too mild. Papillomatous epidermal nevi should also be excluded because they do not respond to the drug. Hailey-Hailey disease may even be worsened by this treatment. According to our experience, oral retinoid therapy has no effect in monilethrix.

Acitretin↗
PubMed1987

Substrate specific sulfatase activity from hair follicles in recessive X-linked ichthyosis.

Recessive X-linked ichthyosis (RXLI) has its biochemical basis in a defect of the enzyme steroid sulfatase. Since several studies have reported a simultaneous deficiency of arylsulfatase C and steroid sulfatase it has been hypothesized that both enzymes are identical. In human hair follicles, however, hydrolytic activity for 4-methylumbelliferone sulfate, the substrate for arylsulfatase C, is found, while dehydroepiandrosterone sulfate is not hydrolyzed at all. These findings suggested the possible existence of two different enzymes. In the present paper structure-activity studies and molecular energy calculations are used for the demonstration that the remaining sulfatase activity in hair follicles of RXLI patients can be explained on the basis of the assumption that the enzyme has not lost its total function but has become less efficient.

Adolescent↗