Search PubMed⌕ Search

Biomedical subjects

Wolfram Sterry

Publications and source records attributed to Wolfram Sterry.

At least 37 records · Page 2Linked to original sources
PubMed2006

An in vivo model to evaluate the efficacy of barrier creams on the level of skin penetration of chemicals.

The reservoir function and the barrier function are important properties of the skin. The reservoir function is dependent on the barrier function which, however, needs support by protective measures, in particular under working conditions. Barrier creams represent a possibility to protect the skin. In the present study, a method was developed to investigate the effectiveness of reservoir closure by different formulations. Patent Blue V in water was used as a model penetrant. Its penetration, with and without barrier cream treatment, was analyzed by tape stripping in combination with UV/VIS spectroscopic measurements. The investigations showed that the stratum corneum represents a reservoir for topically applied Patent Blue V in water. Furthermore, the barrier investigations showed that vaseline and bees wax form a 100% barrier on the skin surface. The third barrier cream, containing waxes and surfactant, only partially showed a protective effect against the penetration of Patent Blue V in water. Strong interindividual differences were observed for this barrier product. In conclusion, it was assumed that the application of barrier creams cannot replace other protective measures and should be maximally used to inhibit low-grade irritants or in combination with other protectants or in body areas where other protective measures are not applicable.

Administration, Cutaneous↗
PubMed2006

Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs.

Due to their structural similarity, interleukin (IL)-19, IL-20, IL-22, IL-24 and IL-26 were combined with IL-10 in the so-called IL-10 family. To expand the knowledge on IL-19, IL-20 and IL-24, we systematically and quantitatively analysed the expression of these mediators and their receptor chains in vitro and in vivo under various conditions and in comparison with other IL-10 family members. In vitro, IL-19, IL-20 and IL-24 were produced not only by activated immune cells, particularly monocytes, but also to a similar extent by keratinocytes. IL-1beta increased the expression of these mediators 1000-fold (IL-19) and 10-fold (IL-20 and IL-24) in keratinocytes. In vivo, these cytokines were expressed preferentially in inflamed tissues. The absence of either R1 chain for the two types of receptor complexes for these cytokines (IL-20R1/IL-20R2 and IL-22R1/IL-20R2) on immune cells implies that they cannot act on these cells. In fact, IL-19, IL-20 and IL-24 did not induce activation of signal transducer and activator of transcription (STAT) molecules in immune cells. Instead, several tissues, particularly the skin, tissues from the reproductive and respiratory systems, and various glands appeared to be the main targets of these mediators. Keratinocytes expressed both receptor complexes; however, the expression of IL-22R1 was 10 times higher than that of IL-20R1. Interferon-gamma further increased the expression of IL-22R1 and decreased that of IL-20R1, suggesting that under T1 cytokine conditions these mediators primarily affect keratinocytes via the IL-22R1/IL-20R2 complex. In summary, these data support the notion that IL-19, IL-20 and IL-24 are distinct from classical ILs and constitute a separate subfamily of mediators within the IL-10 family.

Animals↗
PubMed2006

Clinical Experience Acquired with Raptiva (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from extended treatment in an international, Phase III, placebo-controlled trial.

BACKGROUND: The 12-week, double-blind, placebo-controlled, first-treatment (FT) CLEAR trial period demonstrated the efficacy/safety of efalizumab in moderate-to-severe plaque psoriasis, including refractory or contraindicated patients unsuitable for other systemic treatments. This study assessed the efficacy/safety of open-label extended treatment (up to 24 weeks' continuous treatment) in patients not achieving > or =75% improvement in Psoriasis Area and Severity Index (PASI-75) at week 12 of the FT period. Time to relapse after treatment cessation, and efficacy/safety of 12 weeks' open-label re-treatment in patients achieving PASI-75 at week 12 FT were also assessed. PATIENTS AND METHODS: Patients with PASI-75 at week 12 FT were observed without treatment until relapse, then re-treated with open-label efalizumab (1.0 mg/kg/week for 12 weeks). Others received open-label extended treatment without intervening observation. RESULTS: Among efalizumab-treated patients (n = 308) who had < 75% PASI improvement at week 12 FT, extended treatment led to PASI-75 in 26.6%. Among patients with between > or = 50 and < 75% PASI improvement at week 12 FT (n = 118), 47.5% improved to PASI-75 with extended treatment. For patients achieving PASI-75 at week 12 FT (n = 164), median time to relapse was 58 days. Re-treatment after relapse led to mean PASI improvement of 62.3% from study baseline (n = 145). Safety results were consistent with previous studies, with no new safety concerns. CONCLUSIONS: These results demonstrate additional benefit of continuing efalizumab. Re-treatment re-established disease control in patients with PASI-75 who relapsed following treatment cessation. The safety profile remained consistent with that seen at 12 weeks.

Administration, Topical↗
PubMed2006

Ultrasound-guided fine needle aspiration cytology prior to sentinel lymph node biopsy in melanoma patients.

BACKGROUND: Sentinel lymph node biopsy (SLNB) allows early detection of metastases, thereby enabling early treatment in melanoma patients likely to benefit from adjuvant therapies. This prospective study analyzes the possible benefits of additional ultrasound (US) and fine needle aspiration cytology (FNAC) of sentinel nodes (SN) prior to SLNB. METHOD: Over a 2-year period 127 melanoma patients with 151 SN were scheduled for SLNB. All SN were initially identified with lymphoscintigraphy, then identified and evaluated by US and the cells aspirated for cytology (FNAC). US findings and FNAC results were compared to surgical findings. RESULTS: Of 127 patients, 114 had one SN each, 12 had two, and one had three. In vivo US achieved a sensitivity of 79% (95% CI: 62-91%) and a specificity of 72% (95% CI: 62-81%). FNAC showed a sensitivity of 59% (95% CI: 41-76%) and a specificity of 100% (95% CI: 95-100%). The combination of these two in vivo methods achieved an overall sensitivity of 82% (95% CI: 65-93%) and an overall specificity of 72% [95% CI: 62-81%]. CONCLUSION: Combined US and FNAC provides important information prior to SLNB in that both procedures identify metastases in the lymph nodes (sensitivity > 80%). Patients with positive FNAC may proceed directly to complete lymph node dissection (cLND) instead of having initial SLNB. Thus, combined US and FNAC may prevent unnecessary anesthesia and surgical management as well reduce costs. In our study 16% (19/121) fewer SLNB procedures were carried out, subsequently replaced by cLND. For patients with a negative combination of in vivo US and FNAC, SLNB remains the best diagnostic option.

Adult↗
PubMed2006

The evaluation of psoriasis therapy with biologics leads to a revision of the current view of the pathogenesis of this disorder.

Psoriasis is a common chronic, recurring skin disease that is characterised by typical macroscopic and microscopic skin alterations. It is widely accepted that the immune system plays an important role in the pathogenesis of this disorder. Since the early 1990s, the dominant role of a subpopulation of T cells, so-called T1 cells, and their prominent cytokine IFN-gamma has been assumed in the pathogenesis of psoriasis. Surprisingly, the comparison of the therapeutic success of treatments with recombinant proteins directed against defined immunological structures shows that those that directly affect T cells (alefacept, efalizumab, Hu-max-CD4, OKTcdr4a) were clearly less effective than those targeting TNF-alpha (etanercept, adalimumab, infliximab). For this reason, the authors critically re-evaluated the view of psoriasis pathogenesis and postulate that in the majority of patients the T1 cells do not play a dominant role in the clinical, visible stage of this disease.

Biological Products↗
PubMed2006

Identification of dysregulated genes in cutaneous squamous cell carcinoma.

Carcinogenesis is a multi-step process resulting from the accumulation of genetic mutations and subsequently leading to dysregulated genes, but the number and identity of differentially expressed genes in cutaneous squamous cell carcinoma (SCC) is unknown at present. In order to identify dysregulated genes, we examined the relative mRNA expression present in cutaneous SCC and its precursor lesion actinic keratosis (AK) by comparison to normal skin. Snap frozen biopsies from 20 specimens of normal skin, 10 AK, and 10 cutaneous SCC were examined. Total-RNA was extracted, reversely transcribed, and 14 genes were investigated using gene-specific intron-flanking primers and quantitative real-time reverse transcription PCR. Specificity was confirmed by sequencing of the PCR amplicons. Ten of 14 genes were significantly dysregulated in AK and/or cutaneous SCC by comparison to normal skin. The genes CNN2, COX4I1, COX5B, COX7C, CRLF3, CTSC, NDRG1, and LMNA showed increased expression in skin cancer (p < 0.02), while RPL15 and LGTN were down-regulated (p < 0.03). The genes differentially expressed during skin carcinogenesis may prove useful in order to understand the origin and progression of cutaneous SCC and for diagnostic approaches.

Aged↗
PubMed2005

Pan-selectin antagonism improves psoriasis manifestation in mice and man.

The selectin family of vascular cell adhesion molecules is comprised of structurally related carbohydrate binding proteins, which mediate the initial rolling of leukocytes on the activated vascular endothelium. Because this process is one of the crucial events in initiating and maintaining inflammation, selectins are proposed to be an attractive target for the development of new antiinflammatory therapeutics. Here, we demonstrate that the synthetic pan-selectin antagonist bimosiamose is effective in pre-clinical models of psoriasis as well as in psoriatic patients. In vitro bimosiamose proved to be inhibitory to E- or P-selectin dependent lymphocyte adhesion under flow conditions. Using xenogeneic transplantation models, bimosiamose reduced disease severity as well as development of psoriatic plaques in symptomless psoriatic skin. The administration of bimosiamose in patients suffering from psoriasis resulted in a reduction of epidermal thickness and lymphocyte infiltration. The clinical improvement was statistically significant (P=0.02) as analyzed by comparison of psoriasis area and severity index before and after treatment. Assessment of safety parameters showed no abnormal findings. These data suggest that pan-selectin antagonism may be a promising strategy for the treatment of psoriasis and other inflammatory diseases.

Adult↗
PubMed2005

Long-term therapy of interferon-alpha induced pulmonary arterial hypertension with different PDE-5 inhibitors: a case report.

BACKGROUND: Interferon alpha2 is widely used in hepatitis and high-risk melanoma. Interferon-induced pulmonary arterial hypertension as a side effect is rare. CASE PRESENTATION: We describe a melanoma patient who developed severe pulmonary arterial hypertension 30 months after initiation of adjuvant interferon alpha2b therapy. Discontinuation of interferon did not improve pulmonary arterial hypertension. This patient could be treated successfully with phosphodiesterase-5 inhibitor therapy. CONCLUSION: This is only the 5th case of interferon-induced pulmonary arterial hypertension and the first documented case where pulmonary arterial hypertension was not reversible after termination of interferon alpha2 therapy. If interferon alpha2 treated patients develop respiratory symptoms, pulmonary arterial hypertension should be considered in the differential diagnosis. For these patients phosphodiesterase-5 inhibitors, e.g. sildenafil or vardenafil, could be an effective therapeutic approach.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Identification of noncanonical melanoma-associated T cell epitopes for cancer immunotherapy.

The identification of tumor-associated T cell epitopes has contributed significantly to the understanding of the interrelationship of tumor and immune system and is instrumental in the development of therapeutic vaccines for the treatment of cancer. Most of the known epitopes have been identified with prediction algorithms that compute the potential capacity of a peptide to bind to HLA class I molecules. However, naturally expressed T cell epitopes need not necessarily be strong HLA binders. To overcome this limitation of the available prediction algorithms we established a strategy for the identification of T cell epitopes that include suboptimal HLA binders. To this end, an artificial neural network was developed that predicts HLA-binding peptides in protein sequences by taking the entire sequence context into consideration rather than computing the sum of the contribution of the individual amino acids. Using this algorithm, we predicted seven HLA A*0201-restricted potential T cell epitopes from known melanoma-associated Ags that do not conform to the canonical anchor motif for this HLA molecule. All seven epitopes were validated as T cell epitopes and three as naturally processed by melanoma tumor cells. T cells for four of the new epitopes were found at elevated frequencies in the peripheral blood of melanoma patients. Modification of the peptides to the canonical sequence motifs led to improved HLA binding and to improved capacity to stimulate T cells.

Antigen-Presenting Cells↗
PubMed2005

Expression of human endogenous retrovirus K in melanomas and melanoma cell lines.

The human endogenous retrovirus K family (HERV-K) comprises 30 to 50 closely related proviruses, most of which are defective. In contrast to all other human endogenous retroviruses, some HERV-K proviruses have maintained open reading frames for all viral proteins. In addition to the structural proteins Gag and Env and the reverse transcriptase, two regulatory proteins (Rec and Np9) have been described. Malignant melanoma has the highest mortality among skin cancers and is particularly aggressive. To study the expression of HERV-K, a set of seven primers was developed that allows discrimination between full-length and spliced mRNA and mRNA from deleted and undeleted proviruses. Expression of full-length mRNA from deleted and undeleted proviruses was detected in all human cells investigated. Expression of spliced env and rec was detected in a teratocarcinoma cell line, in 45% of the metastatic melanoma biopsies, and in 44% of the melanoma cell lines. In normal neonatal melanocytes, spliced rec was detected but not spliced env. Viral proteins were shown to be expressed in primary melanomas, metastases, and melanoma cell lines by immunohistochemistry, immunofluorescence, and Western blot analyses using specific antisera. For the first time, antibodies against HERV-K were found in melanoma patients. Melanomas are, in addition to teratocarcinomas and human breast cancer, the third tumor type with enhanced expression of HERV-K.

Adult↗
PubMed2005

Tumour-dendritic hybrid cell vaccination for the treatment of patients with malignant melanoma: immunological effects and clinical results.

Hybrid cell vaccines of autologous tumour cells fused with allogenic dendritic cells (DC) combine the tumour's antigenicity with the immune-stimulatory capacity of mature dendritic cells and allogenic MHC class II molecules to activate T cell help and induce tumour-specific cytotoxic T cells. This concept was tested in a clinical trial with melanoma stage III and IV patients. Seventeen patients were evaluated: one experienced complete, one partial response and six stable disease with long survival times. Eleven of fourteen patients, clinical responders and non-responders alike, mounted high-frequency T cell responses to various tumour-associated antigens. Failing clinical responses correlated with loss of antigenicity.

Amino Acid Sequence↗
PubMed2005

Molecular staging in stage II and III melanoma patients and its effect on long-term survival.

PURPOSE: To assess the prognostic value of serial reverse transcriptase polymerase chain reaction (RT-PCR) -based measurements of tyrosinase mRNA in peripheral blood of stage II and III melanoma patients. PATIENTS AND METHODS: During routine follow-up of American Joint Committee on Cancer stage II and III melanoma patients, serial testing for tyrosinase transcripts in peripheral blood was performed by RT-PCR. The PCR results were compared with the clinical data collected during the follow-up. RESULTS: Over a period of 3 years, 111 patients (78 stage II and 33 stage III patients) were enrolled, and tyrosinase determinations were carried out. The 6-year disease-specific survival probability was 97% for patients always showing negative RT-PCR results and 67% for patients who tested positive at least once. In a Cox proportional hazards model, the prognostic value of sex, age, site of primary tumor, histologic subtype, stage, Breslow's tumor thickness, Clark level, and the time-dependent variable PCR result was assessed. Patients with a positive RT-PCR test had a distinctly higher risk of dying from melanoma, with a hazard ratio of 12.6 (95% CI, 3.4 to 46.3; P < .001). CONCLUSION: Our study shows a strong association between PCR and disease-specific survival time. Detection of tyrosinase mRNA in peripheral blood may be of similar importance for the clinical course of melanoma as the detection of micrometastatic disease in the sentinel lymph node. Whether a combination of these two factors leads to a better definition of the prognosis of melanoma patients is under investigation in current studies.

Adult↗
PubMed2005

WHO-EORTC classification for cutaneous lymphomas.

Primary cutaneous lymphomas are currently classified by the European Organization for Research and Treatment of Cancer (EORTC) classification or the World Health Organization (WHO) classification, but both systems have shortcomings. In particular, differences in the classification of cutaneous T-cell lymphomas other than mycosis fungoides, Sezary syndrome, and the group of primary cutaneous CD30+ lymphoproliferative disorders and the classification and terminology of different types of cutaneous B-cell lymphomas have resulted in considerable debate and confusion. During recent consensus meetings representatives of both systems reached agreement on a new classification, which is now called the WHO-EORTC classification. In this paper we describe the characteristic features of the different primary cutaneous lymphomas and other hematologic neoplasms frequently presenting in the skin, and discuss differences with the previous classification schemes. In addition, the relative frequency and survival data of 1905 patients with primary cutaneous lymphomas derived from Dutch and Austrian registries for primary cutaneous lymphomas are presented to illustrate the clinical significance of this new classification.

Humans↗