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T Hunziker

Publications and source records attributed to T Hunziker.

At least 19 recordsLinked to original sources
PubMed2001

Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (BRAK) in macrophage development.

Although numerous chemokines act on monocytes, none of them is specific for these cells. Here, we show that breast and kidney-expressed chemokine (BRAK) is a highly selective monocyte chemoattractant. Migration efficacy and Bordetella pertussis toxin-sensitive Ca(2+) mobilization responses to BRAK were strongly enhanced after treatment of monocytes with the cyclic AMP-elevating agents prostaglandin E(2) and forskolin. BRAK is the first monocyte-selective chemokine, as other types of blood leukocytes or monocyte-derived dendritic cells and macrophages did not respond. Expression in normal skin keratinocytes and dermal fibroblasts as well as lamina propria cells in normal intestinal tissues suggests a homeostatic rather than an inflammatory function for this chemokine. In addition, macrophages were frequently found to colocalize with BRAK-producing fibroblasts. We propose that BRAK is involved in the generation of tissue macrophages by recruiting extravasated precursors to fibroblasts, which are known to secrete essential cytokines for macrophage development.

Cell Differentiation↗
PubMed2000

[Eosinophilic fasciitis (Shulman syndrome)].

We report on a 35-year-old female with eosinophilic fasciitis (Shulman's syndrome). The characteristic features of this disease are scleroderma-like skin indurations, predominantly on the extremities, with joint contractures and intermittent blood eosinophilia. Histologic findings include fibrosis of muscle fascia and eosinophilic infiltration. Systemic corticosteroid therapy usually results in remission of symptoms. In this case refractory to systemic corticosteroids, we report for the fist time a successful therapy using cyclophosphamide.

Adult↗
PubMed2000

IgG, IgA and IgE autoantibodies against the ectodomain of BP180 in patients with bullous and cicatricial pemphigoid and linear IgA bullous dermatosis.

BACKGROUND: Bullous pemphigoid (BP), linear IgA bullous dermatosis (LABD) and cicatricial pemphigoid (CP) are clinically distinct autoimmune bullous skin diseases characterized by autoantibodies against components of the epidermal basement membrane. Like most patients with BP, a significant subgroup of patients with CP has circulating IgG specific for BP180, a transmembraneous protein of hemidesmosomes. Moreover, sera of patients with LABD contain IgA autoantibodies reactive with a 97/120-kDa protein, LABD antigen 1, which is highly homologous to the extracellular portion of BP180. OBJECTIVES: We aimed to determine whether, in these diseases, autoantibody reactivity to BP180 is restricted to distinct immunoglobulin subtypes. METHODS: Utilizing a baculovirus-encoded form of the ectodomain of BP180, sera from patients with BP (n = 10), CP (n = 9), LABD (n = 10) and normal human control sera (n = 10) were analysed by immunoblot for IgG, IgA and IgE reactivity against BP180. RESULTS: All of 10 BP sera displayed IgG, IgA and IgE reactivity with BP180. Six and seven of nine CP sera, respectively, contained IgG and IgA autoantibodies reactive with BP180, but none of nine sera contained BP180-specific IgE. Nine of 10 LABD sera contained IgA, and six of 10 IgG, which was reactive with BP180, but none of 10 sera showed IgE reactivity to BP180. CONCLUSIONS: The presence of IgG and IgA autoantibody responses to BP180 in patients with three clinically distinct autoimmune bullous diseases indicates that an autoimmune response to the same distinct adhesion protein may lead to different clinical manifestations. It is therefore conceivable that variable epitopes of BP180 are targeted by the different autoantibody isotypes, resulting in the distinct clinical pictures.

Adult↗
PubMed2000

IgG autoantibodies from bullous pemphigoid patients recognize multiple antigenic reactive sites located predominantly within the B and C subdomains of the COOH-terminus of BP230.

Bullous pemphigoid is a subepidermal bullous disorder characterized by an autoantibody response against the bullous pemphigoid antigen 230 (BP230) and the bullous pemphigoid antigen 180 (BP180), a cytoplasmic component and a transmembrane component, respectively, of hemidesmosomes. Although immunodominant sequences within the extracellular domain of BP180 have been identified, characterization of the antigenic sites on BP230 is still incomplete. To identify autoantibody-reactive sites on BP230 and to examine whether the targeted regions are contained within functionally important domains, recombinant fragments encompassing almost the entire BP230 were used to assess the reactivity of 25 bullous pemphigoid sera by immunoblotting. Our results demonstrate that (i) the region bearing the B and C subdomains of the COOH-terminus of BP230 contains immunodominant sequences recognized by the majority of bullous pemphigoid sera; (ii) additional autoantibody- reactive sites are present over extended regions of the NH2-terminal half of BP230 without evidence for antigenic cross-reactivity between the NH2- and COOH-termini of BP230; and, finally, (iii) autoantibodies reacting with the BP230 tail predominantly belong to the IgG4 and IgG1 subclasses, suggesting that both autoreactive TH2 and autoreactive TH1 cells regulate the autoantibody response to immunodominant sequences of BP230. As the COOH- terminus of BP230 mediates the attachment of keratin intermediate filaments to the hemidesmosomal plaque, whereas its NH2-terminus contains sequences important for its interaction with other constituents of hemidesmosomes, autoantibodies to BP230 might precipitate subepidermal blister formation and perpetuate the disease not only by eliciting an inflammatory reaction but also by interfering with the function of BP230 and thus the stability of hemidesmosomes.

Aged↗
PubMed2000

Tumorlike eosinophilic granuloma of the skin.

In 1952, Kuske reported on a patient with a peculiar tumor on the dorsum of the right hand; histological analysis revealed a dense dermal infiltrate with numerous eosinophils. Not aware of any similar case report in the literature, he coined the descriptive term "tumor-like eosinophilic granuloma of the skin." In 1995, a 55-year-old white man with cancer of the prostate presented with a 4-month history of two reddish-brown, solid skin tumors on his left forearm and on the right side of his abdomen, respectively. Histologic examination revealed a dense, superficial and deep, tumorlike dermal inflammatory infiltrate consisting mainly of eosinophils as well as neutrophils and in part epithelioid, in part foamy histiocytes. Flame figures were absent. Immunohistochemical analysis was negative for S-100 protein, whereas sporadic cells in the infiltrate were CD1a positive and many mononuclear-histiocytic cells reacted with MAC 387. Stains as well as cultures for bacteria, mycobacteria, and fungi were negative. The descriptive diagnosis of tumorlike eosinophilic granuloma of the skin was made. Seven weeks after prostatectomy, both tumors resolved spontaneously and so far has not recurred. In our opinion, this is the second report of Kuske's tumorlike eosinophilic granuloma of the skin. Perhaps tumorlike eosinophilic granuloma of the skin, eosinophilic ulcer of the mucosa, and transient eosinophilic nodulomatosis should be considered a mucocutaneous reaction pattern as is seen in cats. In humans, hypersensitivity reactions or atopy could emerge as an etiological link.

Adenocarcinoma↗
PubMed1999

Human melanocytes grown in epidermal equivalents transfer their melanin to follicular outer root sheath keratinocytes.

Because outer root sheath (ORS) cells are valuable substitutes for interfollicular epidermal keratinocytes, we wanted to determine whether epidermal equivalents generated from ORS cells and containing cultured melanocytes can serve as an in vitro model for skin pigmentation. In such epidermal equivalents prepared with ORS cells and melanocytes from donors of phototypes II, III and VI, a stratified epithelium resembling normal epidermis developed within 14 days, as documented by histological, ultrastructural (e.g. basement membrane-like structure, keratohyalin granules, keratinosomes) and immunohistochemical (e.g. keratins, integrins, gp80, involucrin, filaggrin) criteria. The melanocytes were localized in the basal layer and accounted for 10% of the total cell number. Heavily pigmented melanocytes from black donors contained regular melanosomes in all stages of maturation, whereas melanocytes derived from white donors contained predominantly melanosomes of stages I and II. Melanosome-laden dendrites were readily detected extending from the heavily pigmented melanocytes, while they were less conspicuous in melanocytes from white donors. The extent of melanosome transfer was independent of the racial origin of the ORS cells. Melanosomes could also be transferred "through racial barriers". Melanosomes, mainly of stages III and IV, were detected in the ORS cells, being distributed either as single or compound melanosomes, again irrespective of the racial origin of the ORS cells. In conclusion, pigmented epidermal equivalents generated from ORS cells offer practical advantages over other in vitro pigmentation models: (1) the ORS cells are easily and repeatedly available from any donor regardless of age; (2) primary cultures of ORS cells are free of contaminating melanocytes, a bias if using interfollicular epidermal keratinocytes; (3) a high degree of epidermal differentiation is maintained for 3 weeks in fully defined medium, enabling labelling and stimulation experiments to be performed and compounds interfering with melanin pigmentation to be tested.

Biological Transport↗
PubMed1999

Pmg-1 and pmg-2 constitute a novel family of KAP genes differentially expressed during skin and mammary gland development.

The epidermis, by invagination of the undifferentiated ectodermal cells, gives rise to several distinct structures including hair, sebaceous, eccrine sweat and mammary glands. We have recently isolated a novel gene, pmg-1, expressed in the pubertal mouse mammary gland. While investigating its genomic structure, we identified a related gene in close proximity, which we have termed pmg-2. pmg-1 and pmg-2 are intron-less, are transcribed in opposite directions and are separated by a potential promoter region of 2.8 kb containing putative binding motifs for the developmental transcription factors Lef-1, Sox5 and D-STAT. pmg-1 and pmg-2 encode small proteins rich in G, S, F, Y and Q and contain characteristic repeats reminiscent of the keratin-associated proteins (KAPs). Both genes are expressed in growing hair follicles in skin as well as in sebaceous and eccrine sweat glands. Interestingly, expression is also detected in the mammary epithelium where it is limited to the onset of the pubertal growth phase and is independent of ovarian hormones. Their broad, developmentally controlled expression pattern, together with their unique amino acid composition, demonstrate that pmg-1 and pmg-2 constitute a novel KAP gene family participating in the differentiation of all epithelial cells forming the epidermal appendages.

Amino Acid Sequence↗
PubMed1999

Drug-induced linear IgA bullous dermatosis associated with ceftriaxone- and metronidazole-specific T cells.

BACKGROUND: Previous reports indicate that various drugs may induce linear IgA bullous dermatosis (LABD). The role of T cells and T-cell-derived cytokines in the pathomechanism of such skin lesions, however, has remained unclear. OBJECTIVE: To describe a case of LABD induced by ceftriaxone and metronidazole in an 80-year-old female suffering from cholelithiasis with concomitant cholecystitis and provide evidence that drug-specific T cells and their cytokines may contribute to the development of LABD lesions. METHODS: We performed flow cytometry analysis of peripheral blood T cells during LABD, epicutaneous testing (scratch-patch) and lymphocyte proliferation analysis (LTT) with the suspected drugs, routine histological and immunohistochemical examination of the acute skin lesions during LABD as well as of the positive epicutaneous test reactions and measurement of cytokines (IL-4, IL-5, IL-10, TNF-alpha, IFN-gamma) in the supernatant of the LTT cultures. RESULTS: An increased number mainly of activated CD8+ cells was detected in the peripheral blood during LABD. T cell sensitization to ceftriaxone and metronidazole was confirmed by epicutaneous testing and LTT, indicating that these methods may be useful in identifying the causative drugs. Enhanced cytokine levels, particularly of IL-5, were found in the supernatant of the LTT stimulated with ceftriaxone and metronidazole. Furthermore, in situ expression of IL-5 was confirmed in the patient's skin lesions by immunohistochemistry. CONCLUSION: Our findings suggest that in addition to IgA antibodies drug-specific T cells and their subsequent release of cytokines may play an important role in the pathogenesis of drug-induced LABD.

Aged↗
PubMed1998

Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin.

Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a severe adverse drug reaction in which keratinocytes die and large sections of epidermis separate from the dermis. Keratinocytes normally express the death receptor Fas (CD95); those from TEN patients were found to express lytically active Fas ligand (FasL). Antibodies present in pooled human intravenous immunoglobulins (IVIG) blocked Fas-mediated keratinocyte death in vitro. In a pilot study, 10 consecutive individuals with clinically and histologically confirmed TEN were treated with IVIG; disease progression was rapidly reversed and the outcome was favorable in all cases. Thus, Fas-FasL interactions are directly involved in the epidermal necrolysis of TEN, and IVIG may be an effective treatment.

Adolescent↗
PubMed1998

Circadian elevation of IL-6 levels in Muckle-Wells syndrome: a disorder of the neuro-immune axis?

Muckle-Wells syndrome (MWS) is a rare autosomal dominant hereditary disorder characterized by chronic recurrent urticaria, arthralgia, sensorineural deafness, and in some cases nephropathy due to amyloidosis (AA type). We report a 21-year-old woman and her father, both suffering from this syndrome, in whom elevated serum levels of IL-6 could be documented during the flares of urticaria, and discuss the relevance of this finding for MWS.

Acute Disease↗
PubMed1997

[Atopic dermatitis].

Atopic dermatitis is a type of eczema determined by polygenic inheritance which is often associated with further phenotypes of the atopic syndrome such as extrinsic asthma and allergic rhinoconjunctivitis. Discussion of pathogenesis includes complex immunological and biochemical disorders as well as various triggering environmental factors. Characteristic patterns of distribution and morphology of the lesions vary with the patient's age. In addition, there is a broad spectrum of clinical variants. Diagnosis is based on stage-dependent eczematous morphology, if necessary validated by histology, family and personal history and clinical features of atopy, as well as on the results of allergologic assessment primarily comprising intra- and epicutaneous testing. Topical corticosteroids still are the main therapeutic approach.

Administration, Topical↗
PubMed1997

[Erythema elevatum diutinum. A rare dermatosis with a broad spectrum of associated illnesses].

Erythema elevatum diutinum (EED) is a rare disease presenting with persistent red to yellow-brown papules or plaques which are mainly localized symmetrically on the extensor aspects of the hands and fingers, the elbows and the knees. The histology shows a leucocytoclastic vasculitis in early lesions and fibrosis of the dermis later on. Dapsone is the treatment of choice. Today, EED is usually assigned to the neutrophilic dermatoses in which an association with hematological disturbances is well documented. We report on a patient with EED and glioma WHO grade IV, a coincidence unreported hitherto. Additionally, we review the literature on diseases associated with EED.

Adult↗