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Biomedical subjects

T Hunziker

Publications and source records attributed to T Hunziker.

At least 109 records · Page 6Linked to original sources

Post-mitotic human dermal fibroblasts efficiently support the growth of human follicular keratinocytes.

For growth at low seeding densities, keratinocytes isolated from human tissues like epidermis or hair follicles are dependent on mesenchyme-derived feeder cells such as the 3T3-cell employed so far. As an alternative method, the present study describes the use of post-mitotic human dermal fibroblasts sublethally irradiated or mitomycin C-treated. Special emphasis was put on efficient growth of primary keratinocyte cultures plated at very low seeding densities. Thus, outer root sheath cells isolated from two anagen human hair follicles and plated in a 35-mm culture dish (3 - 6 X 10(2) attached cells) grew to confluence within 3 weeks (6 - 8 X 10(5) cells). Similar results were obtained for interfollicular keratinocytes. A crucial point for the function of these fibroblast feeder cells is plating at appropriate densities, considering their tremendous increase in cell size at the post-mitotic state. Plating densities of 4 - 5 X 10(3/cm2 allow full spreading of the feeder cells and do not impede the settling and expansion of the keratinocytes. Major advantages of this system include easier handling and better reproducibility than using 3T3-cells. Moreover, homologous fibroblast feeders mimic more closely the physiologic situation and therefore might provide a valuable tool for studying interactions between human mesenchymal and epithelial cells. Finally, potential hazards of using transformed feeder cells from a different species in keratinocyte cultures raised for wound covering in humans could be thus avoided.

Cell Division↗

[Extensive acrodermatitis chronica atrophicans involving the face].

We report on an 81-year-old woman suffering from extensive acrodermatitis chronica atrophicans with facial involvement. This unusual manifestation may be related to an immunodeficiency state in the course of multiple malignancies. The cutaneous lesions cleared significantly during an aminopenicillin therapy administered orally over 4 weeks.

Acrodermatitis↗

Use of cultured keratinocytes in the treatment of severe burns.

A 6 1/2-year-old child was admitted to the emergency ward for third degree burn injuries representing 40% of body surface. Shock therapy was first applied. After débridement and in a series of operating sessions hands were grafted with full-thickness skin and most other wounds were covered with mesh grafts. On the 14th day after admission a piece of approximately 5 cm2 split thickness scalp skin was used to expand the keratinocytes by cell culture techniques according to the method of Rheinwald and Green (7). After 20 days 4 sheets of cells of first subculture, each 10 cm in diameter, representing a surface of approximately 300 cm2, were implanted on the front of the left thigh, which was burnt third-degree deep. Light microscopy of punch biopsies from mesh grafted and keratinocyte implanted sites taken 5 months after grafting showed a well differentiated epidermis overlying scar tissue. The following conclusions were drawn: Autologous keratinocytes did take on a third degree wound. No basic difference was observed neither clinically nor histologically between mesh-grafted and keratinocyte-implanted sites. The epidermis formed by keratinocyte implantation lacked pigmentation but presented an aesthetically better appearance than the mesh-graft treated sites. Given the scarcity of donor sites and the results obtained by implanting keratinocyte cultures, this latter technique may be resorted to in any extended and deep burn injury.

Burns↗

Plasmin induces acantholysis in skin organ cultures.

Addition of human plasminogen to three different pemphigus plasma samples showed a synergistic effect on acantholysis in the skin organ culture model. Human plasmin itself, without addition of pemphigus plasma, induced typical acantholytic changes in the skin explants, causing different types of acantholysis in a dose- and time-dependent manner: in the presence of 3 CU plasmin per ml culture medium, focal suprabasilar acantholysis of pemphigus vulgaris type could be detected after 72 h incubation, whereas 15 CU/ml caused extended acantholysis of pemphigus foliaceus type in the upper epidermal layers after 24 h, and extended acantholysis of benign chronic pemphigus (Hailey-Hailey disease) type comprising all layers of the epidermis after 48 h incubation. Plasminogen activator levels (Mr 55,000 urokinase type) in tissue extracts of skin explants and in culture media were reduced after 24 and 48 h incubation with pemphigus IgG as compared to control experiments with normal human IgG; this probably resulted from urokinase inactivation by reaction with inhibitors. These results lend support to the hypothesis proposed by Hashimoto et al. in 1983 that the plasminogen activator-plasmin system could play an essential role in the protease mechanisms of pemphigus acantholysis.

Acantholysis↗

Fibronectin in pemphigus.

In the skin organ culture model of pemphigus, fibronectin concentrations of 300 and 500 micrograms/ml inhibited pemphigus plasma-induced acantholysis and intraepidermal binding of the pemphigus antibodies examined by direct immunofluorescence. A direct interaction of fibronectin with pemphigus antibodies could not be demonstrated by chromatography of pemphigus plasma on immobilized fibronectin or by incubation with fibronectin and subsequent precipitation with antifibronectin. We then measured fibronectin concentrations in the plasma of 15 patients suffering from various types of pemphigus and presenting different activities of their disease. Immunoreactive fibronectin levels in untreated patients with active disease were generally in the low normal or even clearly in the subnormal range. They had the tendency to decrease when the disease subsided during therapy with high doses of glucocorticoids, sometimes in combination with azathioprine. The fibronectin concentration in the blister fluid of a patient with acute, untreated pemphigus vulgaris was similar to that in a plasma sample taken at the same time. Skin biopsies of pemphigus patients exhibited an essentially normal fibronectin pattern in direct immunofluorescence. We discuss a possible protective role of fibronectin in pemphigus e.g., by reducing the permeability for pemphigus antibodies in the dermal-epidermal junction zone.

Acantholysis↗

["Aqua-SUP" in chronic palmoplantar dermatoses].

In 11 of 15 patients suffering from chronic dermatoses of the palms and soles (psoriasis inversa, palmoplantar pustulosis, palmoplantar hyperkeratotic eczema and idiopathic pompholyx), an improvement was achieved with "aqua-SUP" therapy. Trials using this therapeutic modality, which is a combination of balneotherapy and selective UV phototherapy (SUP), have only rarely been reported so far. In addition, five patients received internal medication (mainly aromatic retinoid) that had previously not been effective enough, three of them in combination with local corticosteroids. Four more patients were administered local corticosteroids in addition to "aqua-SUP". Four patients experienced local pain in the treated area, especially in the initial phase of phototherapy, and a mild erythematobullous reaction occurred in three of them. No other side-effects were observed. The efficacy of "aqua-SUP" for the treatment of the above-mentioned dermatoses lies in the same range as that of local PUVA, which has been used up to now. However, as "aqua-SUP" is easily manageable, it is more convenient for the patient and does not involve the problems of photosensitization.

Adult↗

[Peroral long-term treatment of psoriasis using fumaric acid derivatives].

Oral treatment of psoriasis on an outpatient basis, using a preparation containing fumaric acid derivatives, was evaluated as initial monotherapy (3 months) and as long-term basic therapy (12-14 months) in 13 and 11 patients, respectively. The course of the disease was analysed in each individual case. After completion of both parts of the trial, half of the patients that had only responded poorly to conventional antipsoriatic therapy showed a significant improvement which occurred after several weeks of treatment. In 4 patients the medication had to be stopped because of abdominal pain. No severe side effects, particularly of a renal, hepatic or haematological nature, could be established. Studies in mice and rats disclosed only a low acute toxicity of the fumaric acid derivatives used. In additional analyses, hypotheses were dealt with concerning the mechanism of action of fumaric acid in psoriasis. To establish fumaric acid derivatives in the treatment of psoriasis, studies on chronic toxicity and pharmacokinetics will have to be conducted. Further clinical trials should evaluate a single fumaric acid derivative instead of mixtures.

Animals↗

[Peroral nickel provocation in nondyshidrosiform and dyshidrosiform nickel eczema].

The flare-up of pompholyx-type nickel eczema induced by oral nickel challenge has been dealt with in several publications. To compare the reactivity of non-pompholyx and pompholyx-type nickel eczema, we challenged three groups of female volunteers (7 with non-pompholyx-type and 12 with pompholyx-type nickel eczema plus 10 control subjects without nickel allergy) with an oral dose of 2.5 mg nickel. By patch testing we additionally determined the degree of cutaneous nickel sensitivity using a series of nickel sulfate dilutions (5.0-0.00001%) and an possible cobalt allergy using 1% cobalt chloride. In 8 of the 19 patients with nickel allergy, the oral nickel challenge was positive (rash, flare-up at sites of healed eczema and former nickel patch tests, and worsening of preexisting eczema; acute pompholyx lesions only in patients with pompholyx-type eczema). The positive results showed the same frequency in non-pompholyx eczema (43%) as in the pompholyx type (42%). Moreover, no substantial difference was found in the degree of cutaneous nickel sensitivity between the two groups of eczema, and there was no correlation between these results and the outcome of the oral nickel challenge. An additional cobalt allergy was recorded significantly more often in pompholyx-type eczema (P = 0.048), yet there was no influence on the oral nickel challenge. The laboratory parameters examined (differential white cell count and total IgE) did not differ in either of the two eczema groups and did not change substantially during nickel challenge reactions.

Administration, Oral↗

[Removal of tattoos with the Nd:YAG laser].

Irradiation of 20 tattoos using the Q-switched Nd:YAG laser (energy density 3-5 J/cm2, asymmetrical pulse shape with 50% energy output in 18 ns, spot size 3 mm in diameter) gave the impression that black ink tattoos can be completely removed without scarring. Some patients needed several treatments. The results continued to improve even some months after the irradiation. In preliminary experiments on excised tattooed and untattooed skin the non-Q-switched Nd:YAG laser had distinct burning effects. It was therefore not tested in patients. The results of chemical, physical, and histological examinations are discussed with special reference to toxic side-effects that might be induced by laser irradiation.

Humans↗

Thalidomide-induced peripheral neuropathy. A prospective clinical, neurophysiological and pharmacogenetic evaluation.

Prospective clinical and electrophysiological follow-up was performed on nine patients under thalidomide treatment in order to detect the very beginning of possible drug-induced peripheral neuropathy. For neurophysiological assessment, nerve conduction measurements of the median, peroneal and sural nerves (7 conduction parameters) and needle EMG examination of the anterior tibial muscle were performed. The results of a first control after about 3 months of treatment were compared with the starting point examination, and the patients were then classified as "affected" or "not affected" according to clinical and neurophysiological criteria. At this point, three patients showed clinical and electrophysiological, and another two only electrophysiological alterations suggesting early neuropathy. This classification did not change after further clinical and electrophysiological controls. Without starting-point values, the early detection of neuropathy would not have been possible in all patients. No single reliable neurophysiological parameter for detection of thalidomide-induced neuropathy could be found. Pharmacogenetic classification with regard to hydroxylation and acetylation phenotypes was then performed in some patients and interpreted with relation to thalidomide neurotoxicity. A possible relationship between slow acetylators and development of thalidomide-induced neuropathy was found.

Acetylation↗