Search PubMed⌕ Search

Biomedical subjects

E Christophers

Publications and source records attributed to E Christophers.

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

Co-localized overexpression of GRO-alpha and IL-8 mRNA is restricted to the suprapapillary layers of psoriatic lesions.

Epidermal infiltration by polymorphonuclear cells is a prominent feature in psoriatic lesions. Expression of neutrophil-specific chemoattractants by lesional keratinocytes could play an important role in the regulation of this infiltration process. We therefore examined the mRNA expression of GRO-alpha, a well-characterized peptide with neutrophil-specific activation profile in psoriatic lesions by in situ hybridization. Clusters of clearly detectable and in some cases highly abundant GRO-alpha hybridization signals could be demonstrated in the differentiated layers of psoriatic epidermis. The signals were clearly associated with keratinocytes, with no nearby neutrophils detectable by microscopic examination. When additional tissue sections of GRO-alpha-expressing lesions were examined with an interleukin-8/neutrophil-activating peptide-8 (IL-8)-specific anti-sense probe, IL-8 expression was detectable and confined to areas also expressing GRO-alpha. Expression of both GRO-alpha and IL-8 is focally upregulated by an as yet unknown mechanism in lesional psoriatic keratinocytes, ultimately leading to neutrophil tissue infiltration. We suggest that the focal expression of GRO-alpha and IL-8 in the epidermal layers above the dermal papillae may be involved in the "squirting papilla" reaction described as a characteristic feature of psoriatic plaque-type lesions.

Cadherins↗
PubMed1996

[LILAs (lipid-like leukocyte activators) isolated from Saccharomyces cerevisiae induce calcium mobilization in human neutrophilic granulocytes[].

Recently, we isolated some new and functionally identical panchemotactic factors (Lipid-like leucocyte activators = LILAs) from Candida albicans, Saccharomyces cerevisiae and various dermatophytes, which are chemotactic for human neutrophilic and eosinophilic granulocytes as well as for monocytes. In order to answer the question, whether human neutrophilic granulocytes express a specific receptor for LILA, we now investigated the mobilisation of the intracellular second messenger calcium within human neutrophils which were stimulated with LILA. Furthermore, LILA-mediated activation of neutrophils was subjected to desensitisation experiments with the well known neutrophil activators 5-oxo-eicosatetraenoic acid, leukotriene B4, platelet activating factor, C5a, Interleukin-8, and N-for-myl-methionyl-leucyl-phenylalanin (FMLP). The intracellular calcium concentration was measured by use of the fluorescence indicator FURA-2/AM. As a result we were able to show a significant dose-dependent increase in the intracellular calcium concentration after stimulation of human neutrophils with LILA. The desensitisation experiments revealed no cross-desensitisation between LILA and the well known stimuli. Our results show that LILA induces an intracellular calcium signal in addition to its panchemotactic activities. Therefore, calcium may act as second messenger in LILA-stimulated activation of neutrophils. Since LILA-mediated activation was maintained in the desensitisation experiments, LILA-specific receptors may be present on human neutrophils.

Calcium↗
PubMed1996

Psoriasis: mechanisms and entry points for possible therapeutic interventions.

Psoriasis is a heterogeneous disorder not only in regard to its variability in clinical expression and age at onset, but also in the degree to which genetic and immunological factors such as T cells and cytokines contribute. A Psoriasis Treatment Index' is proposed according to clinical severity and hence suggested treatment regimens. Recent and new treatments include FK 506, cyclosporin, a fusion protein of human interleukin 2 with fragments of diphtheria toxin, topical tumour necrosis factor inhibitors, topical retinoids, T cell receptor peptide vaccines and intercellular adhesion molecule 1 (ICAM-1) antisense oligonucleotides.

Clinical Trials as Topic↗
PubMed1996

The immunopathology of psoriasis.

Psoriasis affects approximately 2% of the population in Western countries. Although clinically rather monomorphic, the disease presents with a number of phenotypically distinct and heterogeneous subgroups showing differences in their pathogenetic pathways. Patients with type I (early onset) psoriasis demonstrate inflammatory lesions with epidermal hyperproliferation and the presence of activated T cells as well as intraepidermal polymorphs as principal features. In contrast to pustular types of psoriasis, these patients show genetic susceptibility and strong association with MHC class I and class-I haplotypes. There is evidence for a T-cell-mediated pathomechanism leading to a large spectrum of regulatory mediators including cytokines and growth factors as well as lipid mediators which are abnormally expressed. Pathogenetically psoriasis shows features in common with chronic relapsing T-cell-mediated diseases including Crohn's disease, rheumatoid arthritis and others.

Humans↗
PubMed1996

Nodular balloon cell component in a cutaneous melanoma of the superficial spreading type.

The rare histopathologic feature of a nodular balloon cell component in a malignant melanoma of the superficial spreading type in a 46-year-old male patient is presented. Immunohistochemical analyses proved the tumor cells to express the melanocytic markers S100 protein, NK1/C3 and HMB 45 antigens in an intense and distinct pattern. The controversial theories of the pathogenesis of balloon cell changes in melanocytic neoplasms are discussed.

Biomarkers↗
PubMed1996

Interleukin-8 immunoreactivity in malignant tumours of the skin.

In the past, interleukin-8 (IL-8) could be demonstrated within keratinocytes in normal epidermis and inflammatory skin diseases, like psoriasis and eczema. Using monoclonal antibodies, the distribution of IL-8 immunoreactivity was inversely related to the density of inflammatory infiltrate. Other in vitro observations indicated IL-8 to be a growth factor for keratinocytes. These results prompted an immunohistochemical examination of IL-8 immunoreactivity in malignant and semimalignant epithelial tumours of human skin. Whereas IL-8 could not be detected within the transformed cells of epithelial tumours or melanoma, some tumour cells within well differentiated squamous cell carcinoma and Bowen's disease showed IL-8 immunoreactivity. Thus, loss of IL-8 immunoreactivity can be a sign of malignant transformation. This indicates an important role in growth regulation as well as terminal differentiation of human keratinocytes.

Bowen's Disease↗
PubMed1996

Foil bath PUVA in the treatment of prurigo simplex subacuta.

Prurigo simplex subacuta is a chronic pruritic condition of unknown aetiology. The skin lesions respond to topical corticosteroids, UV-A and UV-B therapy only to a limited degree. Ten patients suffering from prurigo simplex subacuta were treated with foil bath PUVA at a concentration of 0.5 mg 8-methoxypsoralen/l. Using the foil bath method the volume of the psoralen/bath-water solution is restricted to 10 l with the aid of polyethylene foil. The group required a median of 13 (95% CI: 9-19) baths for clearance. The total UV-A dose for the whole group was 19 (95% CI:5-30) J/cm2. Bath PUVA is a safe and well-tolerated therapy in the treatment of prurigo simplex subacuta.

Adult↗
PubMed1996

Role of eosinophil-chemotactic C-C chemokines in cutaneous inflammation.

In the dermal sites of atopic skin, eosinophil (Eo) granule protein or more rarely intact Eos represent a characteristic histological feature. We addressed the question of whether lesional scales of patients with various eosinophilic skin disorders contain Eo attractant and tried to characterize it biochemically. In scales of a patient with drug reaction, heparin-binding Eo attractants could be identified. High-performance liquid chromatographic analyses together with specific ELISA and Western blot analyses revealed identity with RANTES. No other heparin-binding Eo chemotaxin could be identified. HPLC analysis of pooled lesional scale extracts of patients with atopic dermatitis showed fractions containing only weak heparin-binding Eo-chemotactic activity, which, however, showed RANTES immunoreactivity. In experiments to elucidate the putative cellular origin of Eo-attracting chemokines in human skin we investigated supernatants of atopic skin we investigated supernatants of atopic skin-derived T lymphocytes as well as supernatants of stimulated dermal fibroblasts for Eo-chemotactic factors. Unexpectedly, we did not find any heparin-bound Eo attractants in supernatants of stimulated cultured atopic skin-derived T lymphocyte clones, whereas fibroblasts produced RANTES as well as granulocyte-macrophage colony-stimulating factor. Therefore, fibroblasts are likely source of eosinophil attractant cells, which could contribute to the Eo infiltrate. Selectivity of the infiltrate might come from selective induction of RANTES and/or induction of other as yet unidentified Eo-specific chemokines.

Animals↗
PubMed1996

Eruptive vellus hair cysts and steatocystoma multiplex. variants of one entity?

Eruptive vellus hair cysts and steatocystoma multiplex are two clinically similar conditions which show multiple papules and nodules, mainly located over the anterior chest wall. Most cases can be differentiated on histological examination, but in some patients overlapping histological features have been described. We present a patient who showed features of both entities and interpret this as suggesting that eruptive vellus hair cysts and steatocystoma multiplex are variants of one disorder which originates in the pilosebaceous duct.

Adult↗
PubMed1995

Lesional elastase activity in psoriasis. Diagnostic and prognostic significance.

Human leukocyte elastase, a neutrophil-derived serine protease, is present in psoriatic lesions in an enzymatically active form. Our purpose was to assess the significance of human leukocyte elastase determinations in estimating the inflammatory activity of psoriatic lesions. A standardized method was used to analyse lesional elastase activity. Elastase activities were correlated with erythema, induration and hyperkeratosis of psoriatic lesions in 54 patients. Lesional elastase activities were also determined during treatment with salt-water bathing and UVB irradiation. Lesional elastase activity correlated with skin induration and was inversely correlated with hyperkeratosis of the lesions. Psoriatic lesions with high elastase activity responded well to therapy, whereas lesions with low elastase activity appeared to be comparatively resistant. This study shows that by quantitative determination lesional elastase activities it is possible to distinguish predominantly inflammatory from predominantly hyperproliferative psoriasis. The latter shows delayed responsiveness to topical therapy with salt-water bathing plus UVB irradiation.

Adult↗
PubMed1995

[Von Recklinghausen neurofibromatosis and dermal melanocytic nevi].

Neurofibromas, café au lait macules and freckles in the axillary or inguinal regions are common manifestations of von Recklinghausen's neurofibromatosis (NF-1). Less known is the simultaneous appearance of dermal melanocytic naevi. We describe the case of a 21-year-old Vietnamese woman who showed generalized, multiple neurofibromas, a solitary plexiform neurofibroma in the left gluteal region and Lisch nodules. In addition, there were several large grey-blue macules histologically characterized by fusiform pigment-bearing cells in the dermis, which we diagnosed as persistent aberrant mongolian spots. In the right zygomatic region she presented a grey-blue, hair-bearing macule, which we saw as a variant of Ota's naevus. A genetic background for this coincidence of a systemic with a local phakomatosis can be supposed, as both Schwann's cells and melanocytes are derived from the neural crest. Such pathologic rearrangement in the embryogenesis of the cellular elements could be important for the pathogenesis of NF-1 and dermal melanocytic nevi.

Adult↗
PubMed1995

Disease concomitance in psoriasis.

BACKGROUND: Psoriasis is a multifactorial disease of unknown origin. OBJECTIVE: Our purpose was to determine the frequency of skin disorders concomitantly seen in patients with psoriasis. METHODS: We analyzed data from more than 40,000 patients and calculated sex- and age-adjusted ratios of expected and observed incidence rates of associated disorders. RESULTS: The results demonstrate that, compared with age-matched control patients without psoriasis, cutaneous immune disorders such as allergic contact dermatitis, atopic dermatitis, and urticaria are underrepresented in patients with psoriasis. In contrast, certain systemic disorders such as diabetes, heart insufficiency, and obesity occur significantly more often in patients with psoriasis than in control subjects. Increased resistance to cutaneous bacterial infections was noted only in patients with early-onset psoriasis. CONCLUSION: Our observations show that a distinct pattern of associated diseases exists in patients with psoriasis. Although systemic disorders such as obesity, diabetes, and heart disease may be related to dietary habits and nutritional status, the relative resistance to cutaneous infections together with decreased immune responsiveness suggest a genetically determined selection.

Adult↗
PubMed1995

Long-term maintenance therapy with cyclosporine and posttreatment survey in severe psoriasis: results of a multicenter study. German Multicenter Study.

BACKGROUND: Although cyclosporine has been found to be effective therapy for severe psoriasis, only limited data exist about efficacy and safety during long-term treatment with a low-dose regimen. Furthermore, little is known about the course of psoriasis after drug withdrawal. OBJECTIVE: Our purpose was to assess the results of long-term therapy with cyclosporine for severe psoriasis with particular regard to efficacy and safety, as well as the disease course after stopping treatment. METHODS: A multicenter study of 217 patients treated with 1.25, 2.5, or 5.0 mg/kg per day of cyclosporine was performed. Duration of treatment ranged from 6 to 30 months followed by a posttreatment period of 3 months. Efficacy was assessed by the Psoriasis Area and Severity Index and safety was monitored by clinical and laboratory investigations. RESULTS: Patients with severe psoriasis showing a reduction in the Psoriasis Area and Severity Index of 75% with their individual dose of cyclosporine maintained clinical improvement during continuous maintenance therapy. Newly occurring side effects were less frequent during the maintenance phase than in the induction phase. After withdrawal of cyclosporine, worsening of psoriasis requiring antipsoriatic therapy was seen in about half of the patients. CONCLUSION: Cyclosporine is effective for long-term therapy for severe psoriasis and does not lead to severe deterioration of the disease after drug withdrawal.

Administration, Cutaneous↗
PubMed1995

Diabetes mellitus in cancer patients treated with combination interleukin 2 and alpha-interferon.

Diabetes mellitus is thought to be an autoimmune disease caused by destruction of beta cells in pancreatic islets. Insulin resistance in the peripheral tissues may also play a role. Both interleukin 2 (IL-2) and alpha interferon can enhance immune function by stimulating formation of cytolytic T cells and/or antigen expression on both normal and tumor cells. This report describes three patients with advanced malignancy who were treated with combination IL-2 and alpha interferon who had the onset or worsening of diabetes mellitus. One patient died as a result. There is evidence that interferon can increase insulin resistance and it is likely that both agents can initiate or enhance an ongoing autoimmune process. Physicians using this combination of drugs should be aware of this potential serious toxicity.

Carcinoma, Renal Cell↗
PubMed1995

Antiprotease activity in urine of patients with inflammatory skin disorders.

Polymorphonuclear leukocytes contain well-defined proteolytic enzymes in their azurophilic granules that can be released into tissues during inflammation, producing a localized excess of proteases that causes a protease-antiprotease imbalance with subsequent tissue destruction. The antiproteolytic compounds of the epidermis, such as the protease inhibitors elafin and antileukoprotease, are thought to counteract the proteolytic tissue damage. We investigated the urine of patients suffering from inflammatory skin conditions (e.g., erysipelas, psoriasis) for the presence of urinary antiprotease activities. Purification of elastase-inhibitory activities from pooled urine samples by cation exchange high-performance liquid chromatography and preparative and analytical reverse-phase high-performance liquid chromatography yielded two different types of inhibitors. One was a cationic, acid-stable, and elastase-specific inhibitor of M(r) 6,000 by size-exclusion high-performance liquid chromatography. N-terminal amino acid sequence analysis of the first 28 residues showed identity with elafin, an elastase-specific inhibitor recently isolated from psoriatic scales. The second anti-protease activity was due to two forms of urinary bikunin, the inhibitory subunit of inter-alpha-inhibitor. Both bikunin fragments, with M(r) 4,000 and 16,000, were identified by N-terminal amino acid sequence analysis of the first 10 residues and were characterized by an antiproteolytic profile against human leukocyte elastase, cathepsin G, and trypsin. Urinary protease inhibitors may serve as diagnostic markers of inflammatory diseases.

Amino Acid Sequence↗
PubMed1995

Detection of the chemokine RANTES in cytokine-stimulated human dermal fibroblasts.

A novel family of structurally and functionally related polypeptides has recently been detected that are now referred to as chemokines. Within this family, a peptide with the acronym RANTES was shown to be chemotactic for memory T cells, monocytes, and eosinophilic and basophilic granulocytes, thus suggesting it plays an important role in chronic inflammatory and allergic diseases. Murine monoclonal antibodies as well as cDNA probes specific for human RANTES were raised and extensively characterized. With these antibodies, stimulated human dermal fibroblasts were shown to express intracellular RANTES peptide by immunocytochemistry. Furthermore, similar kinetics could be demonstrated in fibroblasts for both RANTES mRNA expression and secretion of RANTES peptide using Northern blot hybridization and sandwich-enzyme-linked immunosorbent assay, respectively. RANTES expression was induced upon stimulation with tumor necrosis factor-alpha as well as with interleukin-1 alpha and -beta in a concentration- and time-dependent manner. These results reinforce the role of both resident and circulating cells in the production and release of RANTES and their participation in inflammatory processes.

Antibodies, Monoclonal↗
PubMed1995

Efficacy and tolerability of multiple-dose SDZ IMM 125 in patients with severe psoriasis.

Although cyclosporin is effective in immunosuppression following organ transplantation and in the treatment of psoriasis, its use is limited by its side-effects, notably impaired renal function and hypertension. As SDZ IMM 125, a new derivative of the cyclosporin family, showed considerable immunosuppressive activity in experimental studies, with less effect on renal function, it was considered a potential successor to cyclosporin for both indications. In this multicentre, double-blind, placebo-controlled study, the efficacy and tolerability of 40, 100, 200 and 400 mg SDZ IMM 125 daily were studied in 59 patients with psoriasis. Patients were followed for a period of 5 weeks (4 weeks treatment, and 1 week post-treatment observation). A dose-dependent effect of SDZ IMM 125 was observed. A significant correlation was found between the dose of SDZ IMM 125 and changes in the sum of severity scores of three indicator plaques. There was a significant decrease in the body surface area affected by psoriasis in the 400-mg group (P < or = 0.01), whereas a decrease of the global psoriasis severity was observed in the 200-mg (P < or = 0.01) and the 400-mg groups (P < or = 0.001). No serious adverse events occurred during the 4 weeks of treatment. Three patients discontinued treatment because of adverse events (one sore throat, two influenza). Clinical adverse events were similar to those reported with cyclosporin, the most frequent being gastrointestinal disturbances. Estimation of renal function indices showed that increases from baseline values were dose-dependent, and appeared to be similar to those seen with cyclosporin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗