Recently, the reverse-transcription polymerase chain reaction (RT-PCR) of tyrosinase messenger RNA (mRNA) was reported to be a useful tool for the detection of circulating tumor cells in the ...peripheral blood of melanoma patients. Our aim was to evaluate critically the diagnostic value of this marker by investigating a significant number of patients in different stages of the disease in a two-center study.
Different techniques of blood collection, RNA isolation, and RT-PCR were compared, and the detectability of tyrosinase mRNA was tested using nine different melanoma cell lines. The sensitivity of the method was confirmed by blood spiking experiments and the specificity by restriction enzyme analysis. Subsequently, a total of 153 blood samples from 137 individuals (30 healthy subjects, five basal cell carcinoma, and 102 melanoma patients) were investigated.
The detection level of melanoma cells differed between the cell lines tested. However, we could reproducibly detect single melanoma cells by spiking whole blood samples from healthy volunteers. One of 43 patients with primary melanoma (2.3%), zero of 15 patients with regional metastasis (0%), and 12 of 44 patients with advanced disease (27.3%) were found to be RT-PCR positive. All blood samples obtained from controls and patients with basal cell carcinoma were tyrosinose mRNA negative.
Our data support the recent doubts that the detection of circulating tumor cells in melanoma patients using the tyrosinase mRNA RT-PCR is not sensitive enough to be used either as a melanoma progression marker in early stages of the disease or to monitor therapy in advanced stages of the disease.
Previous studies have shown that oral PUVA is effective in urticaria pigmentosa. Long-term results, however, are unknown.
We studied the long-term effectiveness of oral PUVA treatment in urticaria ...pigmentosa as well as in systemic mastocytosis. In addition, the success of bath PUVA was examined in these diseases.
Twenty patients with urticaria pigmentosa and systemic mastocytosis treated by oral PUVA were examined retrospectively for a time period of up to 18 years. We studied the duration of improvement and correlated these results with the total PUVA dose, the skin type and the age of onset. Four patients were treated by bath PUVA therapy.
In oral PUVA therapy an improvement was seen in 14 out of 20 patients (70%). There was no difference in the response rate between urticaria pigmentosa and systemic mastocytosis and there was no correlation with the total PUVA dosage. The duration of the treatment's success ranged from a few weeks to more than 10 years. 25% of the patients showed an improvement for more than 5 years. Patients with onset during childhood and early adolescence and patients with skin types I and II responded favourably to the treatment. Bath PUVA therapy was without effect in our 4 patients.
Oral PUVA is very effective for the long-term treatment of urticaria pigmentosa as well as systemic mastocytosis.
Human healthy skin is continuously exposed to bacteria, but is particularly resistant to the common gut bacterium Escherichia coli. We show here that keratinocytes secrete, as the main E. ...coli-killing compound, the S100 protein psoriasin in vitro and in vivo in a site-dependent way. In vivo treatment of human skin with antibodies to psoriasin inhibited its E. coli-killing properties. Psoriasin was induced in keratinocytes in vitro and in vivo by E. coli, indicating that its focal expression in skin may derive from local microbial induction. Zn(2+)-saturated psoriasin showed diminished antimicrobial activity, suggesting that Zn(2+) sequestration could be a possible antimicrobial mechanism. Thus, psoriasin may be key to the resistance of skin against E. coli.
Background: Profound changes in the metabolism of eicosanoids with increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. ...Free eicosapentaenoic acid (EPA) may compete with liberated AA and result in an antiinflammatory effect.
Objective: Our purpose was to assess the efficacy and safety of intravenously administered fish-oil–derived lipid emulsion on chronic plaque-type psoriasis.
Methods: A double-blind, randomized, parallel group study was performed in eight European centers. Eighty-three patients hospitalized for chronic plaque-type psoriasis with a severity score of at least 15 according to the Psoriasis Area and Severity Index (PASI) participated in a 14-day trial. They were randomly allocated to receive daily infusions with either a ω-3 fatty acid–based lipid emulsion (Omegavenous; 200 ml/day with 4.2 gm of both EPA and docosahexaenoic acid (DHA); 43 patients) or a conventional ω-6-lipid emulsion (Lipovenous; EPA+DHA < 0.1 gm/100 ml; 40 patients). The groups were well matched with respect to demographic data and psoriasis-specific medical history. Efficacy of therapy was evaluated by changes in PASI, in an overall assessment of psoriasis by the investigator, and a self-assessment by the patient. In one center neutrophil 4- versus 5-series leukotriene (LT) generation and platelet 2- versus 3- thromboxane generation were investigated and plasma-free fatty acids were determined.
Results: The total PASI score decreased by 11.2 ± 9.8 in the ω-3 group and by 7.5 ± 8.8 in the ω-6 group (
p = 0.048). In addition, the ω-3 group was superior to the ω-6 group with respect to change in severity of psoriasis per body area, change in overall erythema, overall scaling and overall infiltration, as well as change in overall assessment by the investigator and self-assessment by the patient. Response (defined as decrease in total PASI of at least 50% between admission and last value) was seen in 16 of 43 patients (37%) receiving the ω-3 emulsion and 9 of 40 patients (23%) receiving ω-6 fatty acid–based lipid emulsion. No serious side effects were observed. Within the first few days of ω-3 lipid administration, but not in the ω-6 supplemented patients, a manifold increase in plasma-free EPA concentration, neutrophil leukotriene B
5 and platelet thromboxane B
3 generation occurred.
Conclusion: Intravenous ω-3-fatty acid administration is effective in the treatment of chronic plaque-type psoriasis. This effect may be related to changes in inflammatory eicosanoid generation. (J Am Acad Dermatol 1998;38:539-47.)
In 2,147 patients suffering from psoriasis, evaluation of the age of onset revealed two peaks, one occurring at the age of 16 years (female) or 22 years (males) and a second peak at the age of 60 ...years (female) or 57 years (males). Human lymphocyte antigen (HLA) tissue typing in 112 randomly assigned patients showed that HLA-Cw6, known to be at disequilibrium in psoriasis, is present in 85.3% of patients with early onset. In contrast, 14.7% patients with late onset showed this marker. Parents (father or mother) were affected in approximately half of the patients with early onset and in none belonging to the group with late onset. Furthermore, psoriasis in patients with early onset follows an irregular course and shows a strong tendency to become generalized. On the basis of clearly defined criteria (e.g., age of onset, heritability, and clinical course of disease), nonpustular psoriasis shows two distinct forms, one of which is hereditary, with early onset, and the other is sporadic and occurs in older age.
The growing public health problem of infections caused by multiresistant Gram-positive bacteria, in particular Staphylococcus aureus, prompted us to screen human epithelia for endogenous S. ...aureus-killing factors. A novel 5-kDa, nonhemolytic antimicrobial peptide (human beta-defensin-3, hBD-3) was isolated from human lesional psoriatic scales and cloned from keratinocytes. hBD-3 demonstrated a salt-insensitive broad spectrum of potent antimicrobial activity against many potentially pathogenic microbes including multiresistant S. aureus and vancomycin-resistant Enterococcus faecium. Ultrastructural analyses of hBD-3-treated S. aureus revealed signs of cell wall perforation. Recombinant hBD-3 (expressed as a His-Tag-fusion protein in Escherichia coli) and chemically synthesized hBD-3 were indistinguishable from naturally occurring peptide with respect to their antimicrobial activity and biochemical properties. Investigation of different tissues revealed skin and tonsils to be major hBD-3 mRNA-expressing tissues. Molecular cloning and biochemical analyses of antimicrobial peptides in cell culture supernatants revealed keratinocytes and airway epithelial cells as cellular sources of hBD-3. Tumor necrosis factor alpha and contact with bacteria were found to induce hBD-3 mRNA expression. hBD-3 therefore might be important in the innate epithelial defense of infections by various microorganisms seen in skin and lung, such as cystic fibrosis.
What's new in psoriasis Christophers, E
Journal of the European Academy of Dermatology and Venereology,
November 2000, Letnik:
14, Številka:
6
Journal Article
The CXC Receptor 2 Is Overexpressed in Psoriatic Epidermis Kulke, Reinhard; Bornscheuer, Erika; Schlüter, Carsten ...
Journal of investigative dermatology,
January 1998, 1998-01-00, 1998, 1998-Jan, 19980101, Letnik:
110, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The CXC chemokines interleukin-8 and GRO/melanoma growth-stimulatory activity (GRO-a) are potent activators of neutrophils and lymphocytes, but also stimulate growth and differentiation of ...nonhematopoietic cells like keratinocytes, fibroblasts, and melanocytes. High mRNA and protein levels have been detected in psoriatic epidermis. Chemokine activation of target cells is mediated by specific receptors and two CXC receptors have been described with similar affinity for interleukin-8 but different affinities for GRO-α. In this study, we examined the expression of both CXCR1 and CXCR2 in psoriatic tissue, identifying the target cells of chemokine activation in psoriasis. By immunohistochemistry and in situ hybridization, as confirmed by northern blot analysis and reverse transcriptase polymerase chain reaction, we could detect expression of the CXCR2 in suprabasal lesional psoriatic keratinocytes but not in healthy skin. The CXCR1 could not be localized in psoriatic keratinocytes with immuno-histochemistry and in situ hybridization, but infiltrating cells in the dermal compartment expressed both types of receptors. These data suggest that in addition to neutrophil activation by both CXCR1 and CXCR2, activation of keratinocytes mediated by CXCR2 could contribute to the characteristic epidermal changes observed in psoriasis.
Summary We report an 80‐year‐old man suffering from an angiosarcoma of the scalp. Because of the wide extent of the lesions, surgery was not performed. Instead, the patient was treated with ...electron‐beam radiation. Later, the patient failed to benefit from radiotherapy demonstrated by a local relapse and new malignant lesions. Additionally, a cervical lymph node metastasis appeared for the first time. Subsequently, we successfully administered liposomal doxorubicin (Caelyx®). Shortly after administration of two cycles the scalp angiosarcoma showed a clear regression. Following six cycles, the patient clinically showed a complete remission of all skin lesions and the cervical lymph node; metastasis was confirmed by histology and fine needle aspiration, respectively. Liposomal and pegylated doxorubicin, a cytostatic drug belonging to the anthracyclines, has already shown to be effective and mostly well tolerated in the therapy of acquired immune deficiency syndrome‐related Kaposi's sarcoma and very recently in cutaneous T‐cell lymphoma, too. Caelyx® appears to be a promising alternative to conventional treatment of cutaneous angiosarcoma.
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