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Biomedical subjects

T Hunziker

Publications and source records attributed to T Hunziker.

At least 73 records · Page 4Linked to original sources

Topical photodynamic therapy in verrucae. A pilot study.

BACKGROUND: Topical photodynamic therapy (PDT) has shown good response rates in solar keratoses and superficial skin cancers. OBJECTIVE: To investigate the efficiency and tolerance of PDT in refractory verrucae vulgares. METHOD: In an open pilot study, 6 patients were treated with 5-aminolevulinic acid-PDT and followed up for 2 months. RESULT: One patient showed a complete response, the other 5 patients were treatment failures. CONCLUSION: Topical PDT is probably not efficient in treating verrucae vulgares.

Administration, Cutaneous↗

Outer root sheath (ORS) cells organize into epidermoid cyst-like spheroids when cultured inside Matrigel: a light-microscopic and immunohistological comparison between human ORS cells and interfollicular keratinocytes.

In organotypic cultures, outer root sheath (ORS) cells of the human hair follicle develop into a stratified epithelium largely reminiscent of the epidermis; this apparently reflects their importance during wound healing. In the present study, ORS cells were grown inside a three-dimensional network of extracellular matrix proteins (Matrigel), together with different mesenchymal cells, in an attempt to mimic their follicular environment. Thus, inside Matrigel, ORS cells formed spheroids differentiating toward the center and showing all the markers of epidermal keratinization. Under identical conditions, normal epidermal keratinocytes developed similar spheroids, but of a significantly smaller size. Human dermal fibroblasts and dermal papilla cells, cocultured in the matrix, had a positive influence on both the proliferation and differentiation within both types of spheroids. Epidermal differentiation markers, such as suprabasal keratins, involucrin, filaggrin, gp80 and pemphigoid antigen, were readily expressed in ORS spheroids, whereas hard (hair) keratins were not detectable by immunostaining. Cells positive for an epithelial membrane antigen, strongly expressed in sebaceous glands, were seen in numerous spheroids. In contrast to organotypic "surface" epithelia, the expression and location of different integrin chains was normalized in ORS spheroids, indicating an enhanced mesenchymal influence in this in vitro system.

Biomarkers↗

Complement profiles in human skin lymph during the course of irritant contact dermatitis.

Using microsurgery a superficial peripheral lymph vessel draining the skin of the upper and medial part of the foot was cannulated on the lower leg of two healthy human volunteers. An irritant contact dermatitis was induced 2 days later by the application of 10% sodium lauryl sulphate to the drained skin area. After a further 3 days the spontaneously regressing skin reaction was treated with clobetasol propionate. Lymph was continuously collected in two aliquots per day for 7 days. The levels of total protein, of albumin and globulins, and of complement components of the classical, the alternative and the lytic pathway as well as the C4A and C4B gene products and the regulatory proteins FB, C1INH, C4BP, FH and FI were determined by ELISA and radial immunodiffusion techniques. Postoperatively, the levels of complement proteins and globulins in the lymph were 5-10 times lower than those in normal human serum, but increased during the course of the skin reaction, while the irritant contact dermatitis did not induce a change in their plasma concentration. In comparison to the baseline, the mean values for C1q, C1r, C2, C5, C6, C7, C8, C9, FB, C1INH, C4BP, FH and FI exhibited a 3-5-fold increase, C3, total C4, albumin and the alpha 1-globulin fraction a 6-9-fold increase, and C1s, C4A, C4B, FB and alpha 2-, beta- and gamma-globulins a 10-20-fold increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Comparative analysis of surface antigens in cultured human outer root sheath cells and epidermal keratinocytes: persistence of low expression of class I MHC antigens in outer root sheath cells in vitro.

In the anagen human hair follicle, the epithelial cells from the infrainfundibular portion and the hair matrix cells express markedly lower numbers of major histocompatibility complex class I molecules than interfollicular epidermal keratinocytes. During the catagen phase of the hair cycle, class I expression on these cells increases, and activated macrophages aggregate around the follicle, which has led to the hypothesis that the cells to be resorbed are recognized by virtue of their low class I antigen expression. In the present study, we showed that, in vitro, outer root sheath cells also maintain a lower constitutive expression of MHC class I molecules compared with epidermal keratinocytes. In contrast, other surface antigens such as HLA-DR, -DP and -DQ, ICAM-1, LFA-3 and CD29, which are all known to participate in leucocyte-keratinocyte interactions, were similarly expressed in both cell types. Furthermore, interferon gamma strongly upregulated MHC class I and II and ICAM-1 expression in both cell types, whereas CD29 and LFA-3 remained unaffected. Tumour necrosis factor alpha, to a lesser extent, also upregulated MHC class I and ICAM-1 expression, but not class II expression. The differences in constitutive surface antigen expression of infrainfundibular outer root sheath cells compared with interfollicular epidermal keratinocytes emphasizes a distinct role of this cell type in the hair cycle, and possibly also in alopecia areata.

Adolescent↗

Childhood epidermolysis bullosa acquisita.

We report a 6-year-old boy suffering from acquired epidermolysis bullosa, who presented with extensive lesions of the mucous membranes and disseminated, herpetiform and 'cluster of jewels'-like vesicles and bullae arising on erythematous plaques. Direct immunofluorescence showed linear deposits of IgG and C3 at the epidermal basement membrane zone. Indirect immunofluorescence demonstrated circulating autoantibodies (titre 1:128-1:256) directed at the blister floor of human NaCl-split skin, and reacting specifically with collagen VII of the anchoring fibrils, as demonstrated by immunoblotting. The disease was controlled with a combination of dapsone and prednisone. This case demonstrates the importance of modern immunological techniques in classifying childhood autoimmune bullous diseases, as precise diagnosis is important in determining an appropriate therapeutic regimen.

Autoantibodies↗

Frequency of sensitization to 13 common preservatives in Switzerland. Swiss Contact Dermatitis Research Group.

From February 1989 to January 1990, the Swiss Contact Dermatitis Research Group conducted a 1-year study to examine the frequency of sensitization to a series of 13 common preservatives. A group of 2295 consecutive outpatients with suspected allergic contact dermatitis (age range 7-90 years, with a mean age of 42; 911 males, 1384 females) was tested. The %s of positive reactions to the preservatives studied are as follows, in descending order: formaldehyde 5.7%, benzalkonium chloride 5.5%, Kathon CG 5.5%, thimerosal 4.2%, chlorhexidine digluconate 2.0%, DMDM hydantoin 1.7%, paraben mix 1.7%, chloroacetamide 1.5%, Bronopol 1.2%, imidazolidinyl urea 1.0%, quaternium 15 1.0%, triclosan 0.8%, 2,4-dichlorobenzyl alcohol 0.4%. These relatively high values suggest a heavy exposure of the Swiss population to topical preservatives. Compared to previous studies, the sensitization rate to Kathon CG has stabilized in Switzerland over the last 2 years. Sensitization to formaldehyde portrayed impressive geographical variation, with sensitization rates up to 9% in western and only 3% in eastern Switzerland. The low sensitization rate to parabens argues for their inclusion in a medicament or preservative series, rather than in the standard series.

Administration, Cutaneous↗

Organotypic cocultures as models to study cell-cell and cell-matrix interactions of human hair follicle cells.

In the hair follicle complex interactions of specialized epithelial and mesenchymal cells as well as extracellular components are crucial for regulation of proliferation and differentiation. In order to mimic this situation in vitro, techniques to cultivate follicular cells such as outer root sheath (ORS) cells, hair matrix cells (HMC) and hair papilla cells (HPC) were developed. Human dermal fibroblasts (HDF) and HPC markedly enhanced proliferation of ORS cells when cocultured spatially separated in a two-chamber system, which was more pronounced with postmitotic than with mitotic mesenchymal cells. In organotypic cocultures of ORS cells on HDF- or HPC-populated collagen gels lifted at the air-medium interface, stratified epithelia developed largely reminiscent of the epidermis. The morphology was well structured and differentiation markers were expressed (e.g. suprabasal keratins, filaggrin, involucrin, basement membrane components). Both proliferation and differentiation were dependent on the presence of HDF or HPC. When grown embedded in extracellular matrix (Matrigel) without HDF, ORS cells formed large spheroids with inward directed differentiation. Also herein HDF or HPC sustained both cell growth and balanced, epidermistype differentiation. While in organotypic cocultures with HDF, HMC also organized into stratified epithelia, epidermis-type stratification was prevented by HPC. Similarly, in the presence of HDF, HMC in Matrigel formed keratinizing spheroids, whereas this was largely suppressed in the presence of HPC. However, hair-type differentiation was not observed, suggesting a crucial role of other yet unknown components or of the surrounding matrix.

Antigens, Differentiation↗

Effects of acute, low-dose UVB radiation on the induction of contact hypersensitivity to diphenylcyclopropenone in man.

Healthy volunteers (n = 14, age range 20-31 years, mean 23) were irradiated on the inside of the left forearm on four consecutive days with their individual minimal erythemal dose of ultraviolet B (UVB) prior to sensitization in the same skin area with a 2% solution of diphenylcyclopropenone (DPCP). The reaction patterns were compared with 14 alopecia areata patients (age range 16-69 years, mean 40) starting topical immunotherapy with DPCP, sensitized without prior UVB treatment. Primary allergic reactions occurred in ten volunteers and in four alopecia areata patients. Patch testing on the upper back with serial dilutions of DPCP (1% to 10(-8)%) showed minimal dermatitis-eliciting concentrations ranging from 1 to 10(-4)% (mean 0.19%) in the volunteers as compared with 10(-1) to 10(-8)% (mean 0.025%) in the alopecia areata patients. Two patterns were discernible within the volunteers with respect to the intensity of the primary allergic and elicitation reactions. Ten volunteers reacted in a similar way to the alopecia areata patients, whereas four probands demonstrated very high minimal dermatitis-eliciting concentrations and overall less severe reactions. The DPCP-specific T-cell response using blood macrophages and B lymphocytes as antigen-presenting cells was measured in an in vitro assay in two alopecia areata patients and two volunteers having similar skin reactions as well as in two volunteers with overall less severe skin reactions. B lymphocytes from the alopecia areata patients and the volunteers with similar skin reactions induced a significant DPCP-specific T-cell proliferation exceeding the responses obtained using macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Soluble factors from human hair papilla cells and dermal fibroblasts dramatically increase the clonal growth of outer root sheath cells.

Depending on environmental influences, follicular outer root sheath (ORS) cells in vivo can differentiate either towards interfollicular keratinocytes or, as demonstrated in the rat vibrissa, hair matrix cells. Crucial regulators of both their proliferation and differentiation are the mesenchymal cells of the respective tissues. The interactions of human ORS cells with human hair papilla cells (HPC) or human dermal fibroblasts (HDF) were studied using a two-chamber model separating the two cell types either by a microporous membrane or additionally by a medium layer. The results of 3H-thymidine incorporation studies indicated that ORS cell growth was markedly enhanced in co-culture with either HPC or HDF, the highest stimulatory effect resulting when ORS cells were in close association with the mesenchymal cells. No correlation was found between ORS cell proliferation and IL-6 production in the co-culture system, thus pointing to the secretion by HPC and HDF of growth-promoting soluble factors that are different form IL-6 as well as from EGF, bFGF and insulin present in the culture medium.

Biological Factors↗

Effects of 1 alpha,25-dihydroxy-vitamin D3 and calcipotriol on organotypic cultures of outer root sheath cells: a potential model to evaluate antipsoriatic drugs.

In the human hair follicle, outer root sheath (ORS) cells constitutively express the hyperproliferation-associated keratins 6, 16 and 17 instead of keratins 1 and 10 found in interfollicular epidermis. In organotypic cultures. ORS cells form a stratified epithelium which in many respects resembles psoriatic skin: it has a hyperplastic tissue architecture and a poorly developed granular layer, and expresses hyperproliferation-associated keratins. Therefore, we studied the effects of the antipsoriatic compounds 1 alpha,25-dihydroxy-vitamin D3 (1 alpha,25-(OH)2-D3) and its synthetic derivative calcipotriol on cultured ORS cells. In monolayer cultures, 10(-6) M 1 alpha,25-(OH)2-D3 or calcipotriol completely blocked ORS cell proliferation. This inhibitory effect was substantially reduced at 10(-8) M. Incubation of organotypic ORS cultures with both vitamin D analogues resulted in a marked thinning of the living cell compartment concomitant with a thickening of the horny layer. A reduced expression of differentiation markers such as keratins 10, 16 and 17, involucrin and filaggrin paralleled the thinning of the stratum Malpighi. As determined by quantification of BrdU-positive cells, ORS cell proliferation was apparently not affected by the vitamin D analogues, indicating that these compounds mainly operate by accelerating the differentiation pathway within the suprabasal living cell compartment. No alteration in the expression of the alpha 6- and beta 1-integrin chains was found.

Adult↗

Large increase of Langerhans cells in human skin lymph derived from irritant contact dermatitis.

In order to monitor the kinetics of Langerhans cells in the afferent lymph during contact dermatitis, a superficial peripheral lymph vessel draining the skin of the upper and medial part of the foot was cannulated by means of microsurgery on the lower leg of four healthy volunteers. After 2 days an irritant contact dermatitis was induced by application of 10% sodium lauryl sulphate to the area of skin drained by the cannulated lymph vessel. Three days later the spontaneously regressing skin reaction was treated with clobetasol propionate in two of the subjects. Lymph was collected twice daily for 8 days. Langerhans cells were identified by immunofluorescence microscopy of cytocentrifuge slide preparations from the lymph, using a monoclonal anti-CD1a antibody. In the late phase of the contact dermatitis the output, i.e. both the absolute number and the percentage of Langerhans cells in the lymph dramatically increased. At the end of the experiment, when there were no remaining clinical signs of contact dermatitis, the Langerhans cell output still markedly exceeded the initial values. These results are the first direct evidence in humans that migration of Langerhans cells from the skin to the regional lymph nodes is a major feature of irritant contact dermatitis.

Adult↗

Phenotype of Langerhans cells in human afferent skin lymph derived from allergic contact dermatitis.

By means of microsurgical lymph cannulation human skin lymph derived from the late phase of an elicitation reaction to diphenylcyclopropenone was sampled. Cells were isolated by centrifugation and then treated with mouse anti-CD1a monoclonal antibodies and sheep antimouse antibody-coated Dynabeads. Ultrastructural and immunocytochemical analyses revealed anti-CD1a/Dynabead-rosetted CD1a- and protein S-100-positive cells which did not express monocyte surface markers, but surface antigens such as HLA-DR, ICAM-1 and, in part, LFA-3. In comparison to freshly prepared human epidermal Langerhans cells (LC), a large fraction of these cells contained no or markedly fewer Birbeck granules and exhibited extensive ruffling of the surface. These data suggest that the phenotype of LC in skin lymph derived from the elicitation phase of allergic contact dermatitis is similar to LC cultured in vitro. In the functional concept of LC of our time, these cells correspond to the dendritic cells designated as "veiled".

Adult↗

Pigmentation following long-term bismuth therapy for pneumatosis cystoides intestinalis.

In the recent literature, only a few reports deal with generalized pigmentation caused by bismuth treatment. We report a patient developing generalized pigmentation of the skin and mucous membranes without further signs of chronic bismuth poisoning following long-term administration of bismuth for pneumatosis cystoides intestinalis. Bismuth deposits were documented in a skin biopsy.

Aged↗

Chronic cutaneous infection caused by Mycobacterium gordonae.

We report on a patient with a chronic nodular cutaneous infection histologically presenting with tuberculoid granulomas and growing Mycobacterium gordonae in culture from a biopsy. The lesions were treated surgically. M. gordonae is a potentially pathogenic environmental mycobacterium only rarely causing skin infections.

Chronic Disease↗

Phenotypic modulation of human hair matrix cells (trichocytes) by environmental influence in vitro and in vivo.

Trichocytes, i.e. precursor cells of the hair cortex and medulla, isolated from plucked human scalp hair follicles (HF) were propagated on feeder layers of post-mitotic human dermal fibroblasts (HDF). Cell isolates from five HF routinely yielded about 0.5-1 x 10(5) cells within 3 weeks. When grown as 'surface epithelia' in vitro (on dermal equivalents exposed to air), trichocytes organized into stratified epithelia largely reminiscent of epidermis with regard to both tissue architecture and localization of epidermal differentiation products (keratins K1 and K10, involucrin, filaggrin). However, when HDF in the collagen matrix were replaced by dermal papilla cells (DPC) epidermoid differentiation was largely prevented while still allowing growth and stratification. Epidermal differentiation (keratinization) was virtually complete when trichocytes grown on collagen gels with HDF were transplanted onto nude mice; this was apparent by tissue organization, expression of K1 and K10 and the nearly regular epidermal localization of involucrin. In addition, the deposition of basement membrane components (laminin, type IV collagen, bullous pemphigoid antigen) at the epithelium-collagen interface further increased and was more regular in transplants than in vitro. Cells embedded in Matrigel together with HDF developed large spheroidal structures with inward-directed differentiation and all the epidermal markers found in 'surface' cultures, while only small keratinizing spheroids formed without HDF. In this system co-culture of trichocytes with DPC suppressed almost completely epidermal keratinization. Although typical hair proteins were not detectable, our data clearly demonstrate that: (1) bona fide trichocytes inherit the options for alternative directions of differentiation, and (2) external (in part mesenchymal cell-mediated) influences play a pivotal role in this determination.

Animals↗

[Squamous epithelial cancer of the skin].

The cutaneous squamous cell carcinoma (SCC) is a malignant skin tumor that arises from epithelial keratinocytes and shows some degree of maturation towards keratin formation. After the basal cell carcinoma, it is the second most common form of skin cancer. The occurrence of cutaneous SCC is usually related to the cumulative exposure to ultraviolet light. Therefore, older people are primarily affected, and the main sites are on the head and on the back of the hands. People with fair skin, especially those who sunburn easily but tan poorly, are at increased risk. Other risks factors are exposure to ionizing radiation or chemical carcinogens as well as some chronic inflammatory or degenerative conditions like scars and chronic ulcers. Immunocompromised patients also are at increased risk. This tumor is curable, the main approach is surgical. But in addition to the danger of local tissue destruction, some tumors have a significant rate of metastasis. Once metastasis on lymph nodes or distant sites has occurred, the chances for cure are greatly diminished.

Carcinoma, Squamous Cell↗

[Psoriasis, an autoimmune disease?].

Whereas psoriasis is well defined as a clinical entity for more than a century, the pathogenesis of psoriasis is still open to debate, despite demonstration of multiple abnormalities in cell-kinetics, histomorphology and biochemistry. Recent research indicates altered immune function in psoriatic skin, which may explain some of the phenomena typical for this disease. The role of immunological pathomechanisms in psoriasis is further substantiated by the well-known success of immunosuppressive treatments. However, as long as putative auto-antigens, which are presumed to perpetuate the pathological immune reactions, are not identified, psoriasis cannot be classified as an autoimmune disease.

Autoantibodies↗