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Biomedical subjects

B M Henz

Publications and source records attributed to B M Henz.

At least 127 records · Page 7Linked to original sources
PubMed1996

Retinoic acid affects the expression rate of the differentiation-related genes aryl hydrocarbon receptor, ARNT and keratin 4 in proliferative keratinocytes only.

The environmental contaminant dioxin exerts most of its effects by activating the aryl hydrocarbon receptor (AhR). The AhR is considered to play not only a role in the regulation of xenobiotic metabolism, but also for development, growth, and differentiation. The transcript levels of the AhR and its associated translocator protein (ARNT) were found to increase with ongoing differentiation in the human keratinocyte cell line HaCaT. Correspondingly, in situ hybridization studies in normal human skin revealed an absence of AhR-expression in proliferating basal cells and increasing transcript levels in upper cell layers, in dependence of keratinocyte differentiation. AhR expression in differentiation-deficient hyperproliferative psoriatic skin was markedly decreased. When keratinocytes were continuously treated with 1 microM retinoic acid (RA), the upregulation of AhR- and ARNT-mRNA levels was inhibited as was keratin 4-expression, a marker of HaCaT-keratinocyte differentiation. In contrast, treatment of already differentiated cells with RA did not down-regulate these transcript levels. The mRNA levels of the prevalent retinoic acid receptors in keratinocytes, RAR gamma and RXR alpha, were not influenced by the process of differentiation or by addition of RA. Our data suggest that the regulation of AhR-, ARNT- and keratin 4-expression by RA is indirect and mediated by a yet to be identified factor.

Aryl Hydrocarbon Receptor Nuclear Translocator↗
PubMed1996

Topical calcitriol enhances normal hair regrowth but does not prevent chemotherapy-induced alopecia in mice.

Using a murine model that mimics chemotherapy-induced alopecia (CIA) in humans particularly well, we show here that in contrast to previously reported CIA-protective effects in neonatal rats, topical calcitriol does not prevent CIA in adolescent mice but enhances the regrowth of normally pigmented hair shafts. When, prior to injecting 1 X 120 mg/kg cyclophosphamide i.p., 0.2 microg calcitriol or vehicle alone were administered topically to the back skin of C57BL/6 mice with all hair follicles in anagen, no significant macroscopic differences in the onset and severity of CIA were seen. However, hair shaft regrowth after CIA, which is often retarded and patchy, thus displaying severe and sometimes persistent pigmentation disorders, was significantly accelerated, enhanced, and qualitatively improved in test compared with control mice. Histomorphometric analysis suggests that this is related to the fact that calcitriol-pretreated follicles favor the "dystrophic catagen pathway" of response to chemical injury, ie., a follicular repair strategy allowing for the unusually fast reconstruction of a new, undamaged anagen hair bulb. Thus, it may be unrealistic to expect that topical calcitriol can prevent human CIA, but topical calcitriols may well enhance the regrowth of a normal hair coat.

Administration, Cutaneous↗
PubMed1996

[Histaminosis].

Explore the source record for details and available documents.

Angioedema↗
PubMed1996

AP-2 gene expression and modulation by retinoic acid during keratinocyte differentiation.

The transcription factor AP-2 has been suggested to participate in keratinocyte gene regulation, but its precise role in the processes of keratinocyte proliferation and differentiation is largely unknown. We here report on an increase of AP-2 transcripts in proliferating HaCaT keratinocytes preceding the expression and upregulation of the differentiation-related genes keratin 4 (K4) and Ah-receptor (AhR), but a decrease of AP-2 transcript levels during the process of keratinocyte differentiation. Continuous treatment of the keratinocyte cell cultures with retinoic acid (RA) resulted in a premature downregulation of AP-2 mRNA levels, and the transcripts of K4 and AhR remained at basal levels. Furthermore, addition of RA to already differentiated cells failed to exert any effect on K4- and AhR-mRNA levels. The data suggest a role for AP-2 as an intermediate factor in the pathway of RA action in keratinocyte differentiation, explaining both the downregulation of K4 and AhR transcript levels in proliferative keratinocytes and the loss of RA effects in already differentiated cells. It appears thus that AP-2 plays a pivotal role at the onset of differentiation in still proliferating keratinocytes.

Actins↗
PubMed1996

[Correlation between chronic urticaria and depression/somatization disorder].

In a multicenter study, 100 patients with chronic urticaria were examined with a standardized personality test (Giessen test), a standardized symptom questionnaire (Giessener Beschwerdebogen) and a specially developed questionnaire concerning symptoms, history and behaviour during symptomatic periods. Almost one third of the patients showed elevated scores both for depression and for symptoms that are often associated with depression. It therefore seems worth-while examining such persons more specifically and possibly treating them by psychosomatic methods. The present results do not allow the classification of chronic urticaria as a somatization disorder. Since one-third of the patients had symptoms of depression, combined dermatological and psychosomatic approach may make it possible to offer them an appropriately targeted treatment.

Adolescent↗
PubMed1996

[Women in dermatology. German and other European clinics in a comparison].

The situation of women in dermatology was evaluated with the aid of questionnaires in spring 1994. A questionnaire was sent to 33 clinics in Germany and 46 in other European countries, asking about the proportions of male and female physicians in each department. In addition, individual department members were asked in another questionnaire about their reasons for choosing dermatology and about possible sex discrimination. The clinic questionnaires were returned from 22 German and 37 other European clinics and the individual questionnaires by 548 German physicians and 1164 physicians from the other countries (overall 52% women). We found that 41.8% of the dermatologists in German clinics were women, as against 43.4% in the other countries. Women made up about half of the fully qualified specialists, but accounted for only a small percentage of those in higher positions (10.8% in Germany, 27.9% in other countries). Of the 1712 physicians who answered the individual questionnaire, the majority had chosen dermatology because of their interest in the specialty. Slightly more women than men gave other reasons, such as more free time--mostly for family matters--or less physical strain. Clearly more women than men felt they were discriminated against professionally because of their sex. The reasons for this related primarily to the biological and social role of women in society. Overall, women are thus well represented in our specialty, except in leading positions.

Career Choice↗
PubMed1996

[Plasmapheresis and immunopathogenetic aspects of toxic epidermal necrolysis].

Drug-induced toxic epidermal necrolysis (TEN) is a rare but frequently lethal disease of the skin and mucosa of unknown etiology. Toxic metabolic and immunologic products in the serum have been discussed as possible causes. For this reason we have performed plasmapheresis on these patients for many years. Results regarding survival and healing of the lesions are quite favorable, as exemplified with two patients described here who benefited from the procedure despite their old age. In order to gain insight into possible disease mechanisms that would explain the beneficial effect of plasmapheresis, we did immunohistochemical studies on these patients before and in one case after the procedure. In dermis and epidermis, there was a striking increase of macrophages and a relative increase of CD8-positive lymphocytes which might act as cytotoxic effector cells; these findings can be interpreted as the result of an immunological reaction. An increased staining of lesional epidermis with TNF alpha, as previously noted by other authors, should be interpreted with caution since necrotic cells are involved. On the basis of the clinical results, the pathogenetic considerations, and in view of the lack of specific treatment modalities, clinical studies concerning plasmapheresis for the treatment of toxic epidermal necrolysis are recommended, particularly since this procedure is widely available and generally well tolerated.

Aged↗
PubMed1996

[Successful treatment of chronic discoid lupus erythematosus with argon laser].

We report on a patient with chronic discoid lupus erythematosus who was treated with argon-laser. The patient suffered from long-standing lesions and had been pretreated with various drugs; with no or slight improvement. After a few argon-laser applications, the treated skin lesions improved dramatically while the untreated lesional skin showed continuous disease activity. Histological and immunohistological investigations of biopsies from treated and untreated lesional skin suggest that endothelial mechanisms play a role in the generation and maintenance of discoid lesions in lupus erythematosus. This is the first reported case of successful treatment of chronic discoid skin lesions of a lupus erythematosus patient with argon-laser.

Adult↗
PubMed1996

Metastatic potential of human melanoma cells in nude mice--characterisation of phenotype, cytokine secretion and tumour-associated antigens.

Incidence and mortality of human malignant melanoma has risen rapidly over recent decades. Although the notorious resistance to treatment is characteristic for metastatic malignant melanoma, only a few experimental models have been established to study the metastatic cascade or to test new alternative treatment modalities. Thus, new human models are wanted. Here, we describe the metastatic behaviour of seven human melanoma cell lines derived from two primary cutaneous melanomas (WM 98-1, WM 1341) and five metastases established from liver (UKRV-Mel-4), skin (M7, M13), pleural effusion (UKRV-Mel-2) and lymph node (MV3). All cell lines were analysed for their capacity to grow in nude mice after s.c. and i.v. administration. M13 cells developed liver metastases spontaneously after s.c. injection, and subsequent passages of M13 and M7 melanoma cells caused liver metastases after i.v. injection, whereas MV3 and WM98-1 gave rise to lung metastases, using the same inoculation route. In contrast, WM 1341, UKRV-Mel-2 and UKRV-Mel-4 grew only very slowly in nude mice after s.c. injection and did not cause any metastases after i.v. or s.c. administration. The pattern of metastases or growth kinetics did not correlate with the interleukin 8 or tumour necrosis factor secretion of cell lines. Adhesion molecules and growth factor receptor expression on the cell lines differed widely, as determined by flow cytometry, with the low metastatic cell lines (UKRV-Mel-2, UKRV-Mel-4 and WM 1341) demonstrating a marked reduction in VLA-1 and VLA-5 expression compared with the metastatic lines (M7, M13, MV3 and WM 98-1). Expression of pigment-related proteins such as tyrosinase, TRP-1, TRP-2, Melan-A/MART-1, gp100, MAGE1 or MAGE-3 was not associated with growth and metastatic characteristics of the melanoma cell lines analysed. In conclusion, the established human melanoma cell lines exhibited diverse growth behaviour in nude mice in congruence with some early established prognostic markers such as VLA-1 and VLA-5. The xenografts provide good models for further study of metastatic processes as well as for evaluation of alternative treatment modalities including new pharmaceutical drugs and gene therapeutic targeting using tissue-specific gene regulatory elements for gene targeting.

Animals↗
PubMed1996

Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo.

Human malignant melanoma is notoriously resistant to pharmacological modulation. We describe here for the first time that the synthetic retinoid CD437 has a strong dose-dependent antiproliferative effect on human melanoma cells (IC50: 5 x 10(-6) M) via the induction of programmed cell death, as judged by analysis of cell morphology, electron microscopical features, and DNA fragmentation. Programmed cell death was preceded by a strong activation of the AP-1 complex in CD437-treated cells as demonstrated by gel retardation and chloramphenicol transferase (CAT) assays. Northern blot analysis showed a time-dependent increase in the expression of c-fos and c-jun encoding components of AP-1, whereas bcl-2 and p53 mRNA levels remained constant. CD437 also exhibited a strong growth inhibitory effect on MeWo melanoma cells in a xenograft model. In tissue sections of CD437-treated MeWo tumors from these animals, apoptotic melanoma cells and c-fos overexpressing cells were colocalized by TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ hybridization. Taken together, this report identifies CD437 as a retinoid that activates and upregulates the transcription factor AP-1, leading eventually to programmed cell death of exposed human melanoma cells in vitro and in vivo. Further studies are needed to evaluate whether synthetic retinoids such as CD437 represent a new class of retinoids, which may open up new ways to a more effective therapy of malignant melanoma.

Animals↗
PubMed1996

Production of interleukin-6 by human mast cells and basophilic cells.

Since mast cells and basophils are thought to play a central role in several types of cutaneous inflammatory and allergic reactions, and since interleukin-6 (IL-6) is an important mediator in these processes, we have studied the ability of the human mast cell line HMC-1, the human basophilic cell line KU812, and human skin mast cells to produce IL-6. All three cell types proved to be potent sources of this cytokine after appropriate stimulation. Transcription of IL-6 mRNA was first detectable 2 h after stimulation with the ester phorbol myristate acetate (PMA) and the calcium ionophore A23187 in both cell lines, as evidenced by semiquantitative reverse transcriptase polymerase chain reaction analysis. Whereas resting cells did not produce IL-6 protein, PMA/A23187-stimulated cells released immunoreactive and biologically active IL-6, as demonstrated and quantitated by enzyme-linked immunosorbent assay and by the use of TEPC 1033 cells, an IL-6-dependent murine plasmacytoma cell line. Stimulated KU812 cells secreted sevenfold more IL-6 (up to 15 ng/ml) than HMC-1 cells (up to 2.4 ng/ml). Immunoblotting of HMC-1- and KU812 cell-derived IL-6 revealed several IL-6 forms in the molecular weight range of 21 to 30 kDa. Immunoelectron microscopic studies of human skin biopsies provided evidence that unstimulated mast cells do not contain preformed IL-6 but accumulate IL-6 in cytoplasmic and extruded granules after IgE-dependent stimulation. These findings suggest that IL-6 secreted by human mast cells and basophils potentially contributes to allergic, other immunologically mediated and nonspecific inflammatory responses.

Basophils↗
PubMed1996

Release of stem cell factor from a human keratinocyte line, HaCaT, is increased in differentiating versus proliferating cells.

Stem cell factor, a recently discovered growth factor for hematopoietic stem cells, mast cells, and melanocytes, was initially reported to be produced by fibroblasts. In this study, we investigated the secretion of this factor from human HaCaT cells during in vitro culture and compared it to synthesis by cells in the skin. Release of stem cell factor from freshly cultured keratinocytes was comparable to that of HaCaT cells and was nearly half that produced by fibroblasts and umbilical vein endothelial cells. No stem cell factor was detectable in culture supernatants of melanocytes. HaCaT cells underwent spontaneous differentiation after a period of proliferation until confluency. Depending on duration of culture, they released increasing amounts of stem cell factor (approximately 150 pg/10(6) cells on day 3 (proliferating cells) vs approximately 450 pg/10(6) cells on day 14 (differentiating cells) measured by enzyme-linked immunosorbent assay. Stimulation for 24 h with the calcium ionophore A 23187 (10(-6) to 10(-8) M) further enhanced release. Western blot analysis of HaCaT cell lysates with a stem cell factor antibody revealed two proteins with the known molecular weights of membrane-bound and soluble stem cell factor. By semiquantitative reverse transcriptase polymerase chain reaction, full-length as well as spliced type stem cell factor mRNA was found to be increased in differentiating versus proliferating HaCaT cells. Keratinocytes are thus potentially important sources of stem cell factor in human skin, and HaCaT cells provide a useful model for further studies of stem cell factor from keratinocytes.

Base Sequence↗
PubMed1996

Interactions of immature human mast cells with extracellular matrix: expression of specific adhesion receptors and their role in cell binding to matrix proteins.

Interactions of cells with their extracellular matrix (ECM) are central to tissue-specific migration, localization, and function of migratory cells. Since mast cells circulate as immature precursor cells and home to tissues in a characteristic distribution, with increases in various disease states, we used the immature human mast cell line HMC-1 as a model to investigate the poorly understood mast cell-ECM interactions in humans. Functional adhesion studies showed that HMC-1 cells spontaneously adhere to fibronectin and laminin (80% at 6 and 12 microgram/ml, respectively) and to collagen type I and III (50% at 20 microgram/ml), whereas binding to vitronectin and collagen type IV required cell activation by phorbol myristate acetate. HMC-1 cells did not adhere to hyaluronic acid. Moreover, both fibronectin and laminin supported pronounced cytoplasmatic spreading with formation of isolated lamellipodia, whereas these cells exhibited a round cell shape on collagen and vitronectin, as shown by scanning electron microscopy. On flow cytometric analysis, HMC-1 cells expressed several adhesion molecules including the integrins beta 1, alpha 2 through alpha 6, alpha v, and alpha v beta 5, as well as CD44. Adhesion to fibronectin and vitronectin was found to be divalent cation- and arginine-glycine-aspartic acid-dependent, and could be blocked by antibodies to beta 1 or alpha 5, and alpha v or alpha v beta 5, respectively. In contrast, binding to laminin and collagen could not be blocked by monoclonal antibodies to any of the cell surface adhesion receptors expressed. Our results show that immature mast cells are able to modify their adhesive behavior in response to various ECM proteins and activating stimuli, and that this phenomenon is partly integrin mediated. These findings may be important for our understanding of the mechanisms leading to tissue-specific localization of mast cells.

Cell Adhesion↗
PubMed1996

High-dose ultraviolet A1 (UVA1), but not UVA/UVB therapy, decreases IgE-binding cells in lesional skin of patients with atopic eczema.

In order to further elucidate the mechanisms by which high-dose ultraviolet A1 (UVA1) therapy leads to improvement in patients with atopic eczema, we assessed skin sections from patients before and after high-dose UVA1 therapy (n = 5) or conventional UVA/UVB therapy (n = 4) for changes in Langerhans cells and mast cells expressing the high-affinity IgE receptor Fc epsilon RI and in surface-bound IgE by histochemical and immunohistochemical techniques. The two treatment groups exhibited different patterns of changes in the number of Fc epsilon RI+, CD1a+, and mast cells within the dermis: The density of both Langerhans cells and mast cells was decreased after high-dose UVA1 therapy, but not after UVA/UVB therapy. High-dose UVA1 and UVA/UVB therapy significantly increased the number of CD1a+ cells within the epidermis, but only high-dose UVA1 reduced the relative number of IgE+ intraepidermal Langerhans cells typically found in atopic eczema. Reduction of numbers of dermal Langerhans cells and mast cells, as well as relative numbers of intraepidermal IgE+ Langerhans cells, was closely linked to significant clinical improvement by high-dose UVA1, but not UVA/UVB therapy. These studies support the notion that IgE-binding cutaneous cells are involved in the pathogenesis of atopic eczema. We propose that UVA1 radiation exerts its effects in atopic eczema, at least in part, by inhibiting Langerhans cell migration out of the epidermis and, in particular, by reducing the number of IgE-bearing Langerhans cells and mast cells in the dermis.

Cell Count↗