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Wolfram Sterry

Publications and source records attributed to Wolfram Sterry.

At least 55 records · Page 3Linked to original sources

Differential expression of MART-1, tyrosinase, and SM5-1 in primary and metastatic melanoma.

The new monoclonal antibody SM5-1 has been shown to have significant advantages in immunohistochemistry of melanoma over currently used antibodies such as HMB-45 or anti-S100. In this study we compared the immunohistological staining pattern of SM5-1 with that of the more recently described antibodies A103 (anti-MART-1) and T311 (anti-Tyrosinase) in 344 paraffin-embedded melanoma specimens, consisting of 101 primary melanomas (77 SSM, 16 NM, 6 ALM, 2 LMM) and 243 melanoma metastases. The overall reactivity of SM5-1 for all the specimens was 92% (318/344) compared with 83% (285/344) for MART-1 and 71% (245/344) for Tyrosinase. Staining of melanoma metastases with SM5-1 was found in 91% (222/243), but only in 77% (187/243) with A103 and 63% (154/243) with T311, respectively. Staining with SM5-1 was more homogenous with 196 of 243 (80%) of metastatic lesions showing 50% or more positively stained cells within the lesions, whereas A103 and T311 did so in 141 of 243 (58%) or 117 of 243 (48%) of the lesions. With regard to staining intensity of SM5-1, 157 of 243 (64%) showed a strong or very strong staining intensity, whereas A103 and T311 did so in 85 of 243 (35%) or 70 of 243 (29%) of the lesions. Staining intensity and percentage positivity correlated well for SM5-1, because from the 58 very strong positive metastases 55 showed staining in more than 75% of the cells within a lesion. Importantly, 52 of 56 MART-1-negative metastases and 81 of 89 Tyrosinase-negative metastases were positive for SM5-1. Thirty-eight metastases (15.6%) were negative for both A103 and T311. Of those, 35 (92.1%) were positive for SM5-1, demonstrating the value of SM5-1 in identifying melanoma-associated antigen-negative lesions. We conclude that SM5-1 could be of value in immunohistochemistry of melanoma.

Antibodies, Monoclonal↗

Haplotype sharing analysis identifies a retroviral dUTPase as candidate susceptibility gene for psoriasis.

The psoriasis susceptibility locus 1 (PSORS1) mutation is assumed to reside within a region around human leukocyte antigen-C spanning 250 kb, termed risk haplotype (RH) 1/2. By re-analyzing a published data set with a previously developed method, the haplotype sharing statistic, we confirm localization of PSORS1 to the RH1 region and refine its location to marker M6S168. We replicate this result in an independent patient sample. The target region harbors fragments of a human endogenous retrovirus K (HERV-K) endogenous retrovirus. Two single-nucleotide polymorphisms with alleles differing between high- and low-risk haplotypes are located within the HERV-K dUTPase. One of these encodes a predicted non-conserved Glu-Arg exchange. The HERV-K dUTPase is expressed in peripheral blood and in normal as well as lesional psoriatic skin. Our results indicate that an endogenous retroviral dUTPase constitutes a candidate gene for the PSORS1 mutation.

Chromosomes, Human, Pair 6↗

Differential stripping: determination of the amount of topically applied substances penetrated into the hair follicles.

The determination of penetration pathways of topically applied substances into the skin is the subject of several investigations. Recently, follicular penetration has become a major focus of interest. To date, a direct, non-invasive quantification of the amount of topically applied substance penetrated into the follicles had not been possible. The development of such a method was the aim of this study. Therefore, the advantages of both stripping techniques, tape stripping and cyanoacrylate skin surface biopsy, were combined and evaluated. Tape stripping was used to remove the part of the stratum corneum that contained the topically applied dye. Subsequently, the follicular contents were ripped off by cyanoacrylate skin surface biopsy. The combined method termed "differential stripping" was evaluated in vitro and in vivo, and the amount of topically applied fluorescent dye penetrated into the hair follicles was quantified after different penetration times. After 30 min, 5% of the recovered concentration of sodium fluorescein was found in the follicular infundibula, where it was still detectable after 48 h. Altogether, the results of this investigation revealed that differential stripping is a new method that can be used to study the penetration of topically applied substances into the follicular infundibula non-invasively and selectively.

Administration, Topical↗

WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects.

UNLABELLED: The new WHO/EORTC classification for cutaneous lymphomas comprises mature T-cell and natural killer (NK)-cell neoplasms, mature B-cell neoplasms, and immature hematopoietic malignancies. It reflects the unique features of lymphoproliferative diseases of the skin, and at the same time it is as compatible as possible with the concepts underlying the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. This article reviews the histological, phenotypical, and molecular genetic features of the various nosological entities included in this new classification. These findings always have to be interpreted in the context of the clinical features and biologic behavior. AIM: To review the histological, phenotypical and molecular genetic features of the various nosological entities of the new WHO/EORTC classification for cutaneous lymphomas. METHODS: Extensive review of the literature cited in Medline and own data of the authors. RESULTS: The WHO/EORTC classification of cutaneous lymphomas comprises mature T-cell and NK-cell neoplasms, mature B-cell neoplasms and immature hematopoietic malignancies. It reflects the unique features of primary cutaneous lymphoproliferative diseases. CONCLUSION: This classification is as much as possible compatible with the concept of the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. The histological, phenotypical and molecular genetic features always have to be interpreted in the context of the clinical features and biologic behavior.

Europe↗

[Development of the evidence-based guidelines for psoriasis--a project of the German Dermatological Society (DDG)].

Clinical guidelines have been defined as "systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances". They are designed to evaluate and implement the ever-increasing amount of evidence and opinion on best current practice. They can assist doctors and other health care professionals in making decisions about appropriate and effective care for their patients. Depending on the level of evidence, expert knowledge based and evidence-based guidelines can be distinguished. This article reviews the methods of guideline development, the state of international guidelines in dermatology and the state of the recent German psoriasis-guideline-project.

Evidence-Based Medicine↗

[Efficacy of tracrolimus 0.1% ointment in prurigo].

BACKGROUND: Potent topical corticosteroids are used the intense pruritus in prurigo diseases. Their long-term application leads to local side effects such as atrophy and telangiectasia. PATIENTS AND METHODS: We treated 6 women (average age 64 years) with chronic prurigo with tacrolimus 0.1 % ointment (Protopic) to evaluate its efficacy in this clinical setting. Tacrolimus 0.1% ointment was applied twice a day for 4 weeks. RESULTS: After one week, both clinical improvement and reduced pruritus were observed in all patients. CONCLUSION: Tacrolimus 0.1% ointment represents a therapeutic option for the treatment of prurigo.

Aged↗

Gender-related differences in the physiology of the stratum corneum.

BACKGROUND: Only few studies on gender-related differences in skin physiology have been performed--and they provided conflicting results. OBJECTIVE: In the present study, the effect of gender on the physiology of the stratum corneum was studied. METHODS: The physiological parameters transepidermal water loss, pH value, hydration and sebum content were determined on the flexor forearms of 6 female and 6 male volunteers. In addition, stratum corneum samples, removed by tape stripping, were studied for amount, spectroscopic properties, protein content, and mass. RESULTS: The skin of women was characterized by a significantly higher pH value (5.6 +/- 0.4) than that of men (4.3 +/- 0.4, p < 0.05). Protein absorption was the only other parameter significantly dependent on gender (p < 0.05). Both effects might be caused by differences in human biology, such as hormonal status. CONCLUSION: Therefore, the gender of the volunteers should be considered in dermatologic studies.

Adult↗

Orally administered ethanol: transepidermal pathways and effects on the human skin barrier.

Ethanol intake is associated with a variety of skin diseases. The aim of the present study was (1) to identify the pathways of release of orally administered ethanol through the skin, and (2) to investigate the effects of a single oral dose of ethanol on the penetration of topically applied substances into the skin. Ethanol evaporation via the skin was measured using the new technique of ion mobility spectrometry (IMS). Transepidermal water loss (TEWL) and skin surface temperature were simultaneously measured before and after ethanol consumption. Measurements were performed on skin sites with different stratum corneum (SC) thickness, and density of follicles and sweat glands. These appendages were selectively sealed to investigate their participation in ethanol evaporation. The penetration of a topically applied UV filter substance was studied before and after ethanol consumption after removing the SC with adhesive tape. Ethanol evaporation was measured within 5 min of consumption, while the skin surface temperature remained nearly constant. The sealing of the appendages did not have a significant effect on ethanol evaporation. On the forehead, a higher TEWL value was measured than on the forearm. On both skin sites, an increase in TEWL was observed after ethanol ingestion. No influence of orally administered ethanol on the penetration of the topically applied UV filter substance was observed. The results indicate that ethanol evaporation occurs via the lipid layers without a significant effect on the penetration of the topically applied substance.

Administration, Oral↗

Vaccination with hybrids of tumor and dendritic cells induces tumor-specific T-cell and clinical responses in melanoma stage III and IV patients.

Hybrid cell vaccination was developed as therapeutic approach that aims at stimulating tumor-specific cytotoxic T-cell responses in cancer patients using hybrids of autologous tumor and allogeneic dendritic cells. We tested this concept and the efficacy of the vaccines in inducing clinical and immunologic responses in a clinical trial with melanoma stage III and IV patients. Of the 17 patients evaluated, 1 experienced a complete response, 1 a partial response and 6 stable disease with remarkably long survival times. In 11 of 14 patients analyzed, high-frequency T-cell responses to various tumor-associated T-cell epitope were induced and detectable in the peripheral blood. These immune responses were detected in clinical response patients as well as nonresponders. Failures of clinical responses in all the cases investigated correlated with loss of antigen expression and presentation. Hybrid cell vaccination thus proves effective in inducing tumor-specific T-cell responses in cancer patients.

Adult↗

High sensitivity and reproducibility of immunohistochemistry with microagitation.

We examined the practicability, reproducibility and analytical sensitivity of classical immunohistochemistry (IHC) and IHC with microagitation. Two monoclonal antibodies, Ki-67 (proliferation marker) and p53 (tumor suppressor marker), were used. Consecutive paraffin sections of biopsies of suspicious lesions of patients with non-melanoma skin cancer were used in the study. Reproducibility was examined using specimens from four patients in three independent experiments with antibodies against Ki-67 and p53. Analytical sensitivity of the two methods was determined using serial dilutions in two independent experiments. IHC with microagitation could be carried out without destroying the tissue. The new technique was consistent and reproducible, and no background staining was observed. The primary antibodies Ki-67 and p53 could be used at higher dilutions (four to ten times) with microagitation compared with classical IHC. Microagitation can be used for immunohistochemistry; it was reproducible, highly sensitive, and antibodies could be used at higher dilutions. Further analyses with other antibodies using this technique are warranted.

Biopsy↗

Evaluation of the IRF-2 gene as a candidate for PSORS3.

Type 1 interferon can trigger flares of psoriasis. Hypersensitivity to type 1 interferon signaling causes a psoriasis-like skin disease in mice deficient for the transcription factor interferon regulatory factor 2 (IRF2). The human IRF2 gene is located at a previously identified candidate psoriasis susceptibility locus on chromosome 4q (PSORS3 at D4S1535). Therefore, we tested association of psoriasis with IRF2. We generated a sample consisting of 157 families with a total of 521 individuals. Five novel microsatellite markers were developed and typed, and complemented with three known markers to yield a set of eight markers spaced within 600 kb around the IRF2 gene, three of which are located in the gene. We detected association of IRF2 with type 1 psoriasis at two markers in the IRF2 gene. Haplotype sharing analysis confirmed association of IRF2 with type 1 psoriasis (p=0.0017; pcorr=0.03). The 921G/A SNP in exon 9 was found to obliterate a predicted exon splice enhancer in an allele-specific manner. There was a suggestive increase of homozygosity for the splicing-deficient allele in type 1 psoriasis patients. Our data identify IRF2 as a potential susceptibility gene for psoriasis.

DNA-Binding Proteins↗

Variations of hair follicle size and distribution in different body sites.

For the evaluation and quantification of follicular penetration processes, the knowledge of variations of hair follicle parameters in different body sites is basic. Characteristics of follicle sizes and potential follicular reservoir were determined in cyanoacrylate skin surface biopsies, taken from seven different skin areas (lateral forehead, back, thorax, upper arm, forearm, thigh, and calf region). The highest hair follicle density and percentage of follicular orifices on the skin surface and infundibular surface were found on the forehead, whereas the highest average size of the follicular orifices was measured in the calf region. The highest infundibular volume and therefore a potential follicular reservoir was calculated for the forehead and for the calf region, although the calf region showed the lowest hair follicle density. The calculated follicular volume of these two skin areas was as high as the estimated reservoir of the stratum corneum. The lowest values for every other parameter were found on the forearm. The present investigation clearly contradicts former hypothesis that the amount of appendages of the total skin surface represents not more than 0.1%. Every body region disposes its own hair follicle characteristics, which, in the future, should lead us to a differential evaluation of skin penetration processes and a completely different understanding of penetration of topically applied drugs and cosmetics.

Adult↗

[DRGs in dermatology: results of the DRG evaluation project of the German Society of Dermatology (DDG)].

SUMMARY BACKGROUND: The implementation of a DRG system in Germany--voluntarily since January 1st, 2003, and obligatory after January 1 st, 2004--has led to uncertainty, particularly in the hospitals. There are fears that current well-accepted German diagnostic and therapeutic services may not be properly financed by the new system. In response, the German Dermatologic Society (DDG) in cooperation with the DRG Research Group of the University Hospital Muenster and the German Medical Association carried out a DRG evaluation project in order to investigate the medical and economic homogeneity of the case groups. PATIENTS AND METHODS: 19,403 dermatological cases from 19 hospitals--ten university hospitals and nine non-university hospitals-were collected over a period of four months and then evaluated with regard to their performance, length of stay and cost homogeneity. RESULTS: The data provided the background needed to indicate suspected potential deficiencies for mapping dermatology cases within the German DRG system. Based on the data 10 modifications were formulated and submitted to the InEK by the deadline of March 31st, 2003. CONCLUSIONS: The results of the DRG Evaluation Project show that the G-DRG-Variant Version 1.0 does not offer the necessary possibilities of differentiation to map the broad spectrum of various dermatology services in Germany.

Cost-Benefit Analysis↗