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Biomedical subjects

W Sterry

Publications and source records attributed to W Sterry.

At least 37 records · Page 2Linked to original sources
PubMed2005

Is there an interaction between interleukin-10 and interleukin-22?

Interleukin(IL)-10 and IL-22 are structurally related cytokines. Their heterodimeric receptors consist of the cytokine-specific chains IL-10R1 and IL-22R1, respectively, and the common chain IL-10R2. This study focused on the question of whether IL-10 modulates IL-22 effects and vice versa. This question is important because IL-10 and IL-22 exert anti- and proinflammatory effects, respectively, and, as we show here, are simultaneously present in both systemic and local inflammation. The revealed lacking concomitance of IL-10R1 and IL-22R1 on identical cells excluded any possible interaction between IL-10 and IL-22 apart from the competition for IL-10R2. To study this competition, monocytes and hepatocytes were chosen. The dependence of the cytokine action on IL-10R2 was verified. Interestingly, no influence of IL-22 on IL-10 effects was observed. The same was true when IL-22 was used in complex with IL-22-binding protein. Similarly, no influence of IL-10 was found on IL-22 action. This missing competition seemed to be due to a lack of binding between IL-10R2 and the native cytokines in the absence of their corresponding R1 chain. However, IL-10R2 interacted with defined IL-10- and IL-22-derived peptides supporting the hypothesis that cytokine binding to its corresponding R1 chain creates a binding site on this cytokine for IL-10R2.

Animals↗
PubMed2005

[Periorbital contact eczema].

Periorbital contact eczema is most commonly the result of an allergic contact dermatitis whereas other eczematous skin diseases like atopic eczema or seborrheic eczema occur less frequently. Also, other diseases like autoimmune disorders or rosacea need to be considered. Allergic contact dermatitis is a T-cell-mediated immunological response towards ubiquitous contact allergens. Activated T-cells migrate through the vessels into the skin and produce several inflammatory mediators. Epicutaneous patch testing is an important tool for the diagnosis of contact allergy whereby the allergens are analysed in terms of their ability to induce eczematous skin reaction. Until now the short-term use of corticosteroids are is employed for the treatment of allergic contact eczema. Modern substances with an optimal therapeutic index should rather be used.

Dermatitis, Contact↗
PubMed2005

The porcine snout--an in vitro model for human lips?

The morphology and histology of test sites commonly used to study the penetration of lip products differ significantly from those of the human lip itself. The aim of this study was to investigate whether the porcine snout could serve as an equivalent in vitro model for human lips. The lips of human test subjects and biopsies of porcine snout tissue were compared using histological and microscopic techniques. Using a dermatological laser scanning microscope, the penetration of topically applied fluorescent sodium fluorescein was investigated in vivo on human lips and in vitro on the porcine snout. Biopsies from the in vitro experiments were studied using fluorescence microscopy. Some parts of the porcine snout show a similar morphology and histology as human lips. The stratum corneum (SC) and the epidermis of the porcine snout are thicker than those of human tissue. Both in vivo and in vitro, the topically applied fluorescent dye was detected only on the skin surface and within the uppermost SC layer. These results indicate that porcine snout can be used as an in vitro model for human lips in penetration studies. Both human and porcine tissues exhibit an efficient barrier against the penetration of topically applied substances.

Adult↗
PubMed2005

Systemic eight-cycle anti-CD20 monoclonal antibody (rituximab) therapy in primary cutaneous B-cell lymphomas--an applicational observation.

BACKGROUND: Primary cutaneous B-cell lymphomas (PCBCLs) are characterized by restriction to the skin and a variable but mostly favourable prognosis. Since 1997 the recombinant, chimeric anti-CD20 antibody rituximab has been used in patients suffering from non-Hodgkin's B-cell lymphomas. Different studies have shown that the effectiveness and safety in the treatment of patients with low-grade follicular lymphoma is comparable to or even higher than the standard CHOP chemotherapy. So far it has been unclear whether an extended duration of therapy leads to a benefit for the patients with PCBCL. OBJECTIVES: To evaluate the objective response rate, time to progression, remission quality and histological changes and to compare our data with the literature. PATIENTS/METHODS: Ten patients with PCBCL [eight with follicle centre cell lymphoma (FCCL), one with marginal zone lymphoma (MZL) and one with diffuse large B-cell lymphoma of the leg (DLBCL)] were treated by intravenous application of a chimeric antibody against the CD20 transmembrane antigen (rituximab) with a dosage of eight cycles, 375 mg m(-2) body surface, weekly. RESULTS: The treatment regimen resulted in clinical overall response in 9 of 10 patients, in particular there were seven complete responses (70%) plus two partial responses (20%). The median duration of remission (durable remission, DR) is 23 months (4-30 months) to date. Histological assessment of responses in four patients showed no tumour-specific infiltration. In two patients histology revealed a residual infiltration and in one patient an increasing infiltration. In two patients no histology was taken after treatment; one patient developed a new lesion. No severe side-effects occurred. Observed side-effects were two bacterial infections, two patients with shivering during infusion, one patient with sweating for months and one patient with persisting itching. As expected the B-cell count in peripheral blood was depressed in all patients after infusion. CONCLUSIONS: Intravenous therapy with eight cycles of the anti-CD20 antibody rituximab is a non-toxic and effective treatment for a subset of patients with PCBCL (relapsed, aggressive entity, old patients, multiple lesions) with a long DR.

Adult↗
PubMed2005

Identification of the testis-specific protein 10 (TSGA10) as serologically defined tumour-associated antigen in primary cutaneous T-cell lymphoma.

BACKGROUND: The number of identified tumour-associated antigens for cutaneous lymphoma is still very restricted, which limits the elucidation of the tumour immunology of these malignancies and the development of specific immunotherapies and immunodiagnostics. OBJECTIVES: To identify new serologically defined antigens associated with cutaneous lymphoma. METHODS: A phage expression library of the human testis transcriptom was established and immunoscreened with sera from 100 patients with cutaneous lymphoma and nine with parapsoriasis, and 81 age-matched control donors. Positive expression clones were sequenced to identify the respective antigen. RESULTS: The testis-specific protein 10 (TSGA10) was identified as an antigen recognized by sera of two patients with Mycosis fungoides but not by sera from healthy donors. By reverse transcription-polymerase chain reaction analysis, TSGA10 was found expressed in all cutaneous lymphoma samples tested, various tumour cell lines, testis, peripheral blood mononuclear cells, skin, isolated lymphocytes, keratinocytes and fibroblasts. TSGA10 overexpression had previously been reported for other cancers. CONCLUSIONS: TSGA10 is a new tumour-associated antigen of cutaneous lymphoma.

5' Untranslated Regions↗
PubMed2005

Review of the potential photo-cocarcinogenicity of topical calcineurin inhibitors: position statement of the European Dermatology Forum.

Topical Calcineurin Inhibitors (TCIs) used for the treatment of atopic eczema modify the immune regulatory function of the skin and may have the potential to enhance immunosuppressive ultraviolet (UV) effects. Current recommendations on UV protection in eczema patients treated with PCIs are inconsistent and have given rise to uncertainty and anxiety in patients. Therefore, the European Dermatology Forum (EDF) developed a position statement which reviews critically the available data with regard to the problem, especially analysing and commenting the limitations of rodent models for the human situation. There is no conclusive evidence from rodent trials to indicate that long-term application of TCIs is photococarcinogenic. There is a need for further studies to investigate the validity of mouse models as well as long-term cohort studies in patients using TCIs. Available data suggest that long-term application of TCIs is safe, that there is no evidence of increased skin cancer risk and that it is ethical to treat patients with TCIs when indicated.

Administration, Topical↗
PubMed2005

Estimation of the relative stratum corneum amount removed by tape stripping.

BACKGROUND/PURPOSE: The tape stripping procedure is a suitable minimal invasive tool to study, e.g. the penetration and dermatopharmacokinetics of topically applied substances. In the present study, this procedure was used to remove the stratum corneum (SC) completely and to study the penetration of the UVA filter substance butyl methoxydibenzoylmethane after application in two different vehicles. METHODS: The amount of corneocytes removed by each tape strip from the flexor forearm of human volunteers was determined via their pseudo-absorption. In a second part, the penetration profiles of a UVA filter substance applied in two different vehicles were determined following the developed standard protocol using the tape stripping procedure in combination with UV/VIS spectroscopy. RESULTS: The amount of corneocytes removed by each tape strip was related to the number of tape strips used for removal. Mean values with a deviation of less than 20% concerning the relative amount of SC removed by a constant number of tape strips were obtained. For instance, a relative amount of 66 +/- 12% was removed with the first 20 tape strips, while nearly the complete SC (95 +/- 3%) was removed using 50 tape strips. In addition, these results were used to estimate the relative SC amounts removed, studying the penetration of the UVA filter substance after application in two different vehicles. No significant differences between the distributions of the UV filter substance applied in both emulsions were obtained (P > 0.05). CONCLUSIONS: The reported procedure for the estimation of the removed SC amount provides the possibility to avoid the complete removal of the SC and to compare the penetration characteristics obtained for different volunteers and different products in relation to the relative horny layer profile.

Adhesiveness↗
PubMed2004

Comparison of four different in vitro systems to study the reservoir capacity of the stratum corneum.

Four in vitro test systems were used to study the reservoir capacity of porcine stratum corneum (SC) for flufenamic acid and its drainage via penetration into the deeper skin layers: Franz diffusion cell using full thickness skin and split skin of 300 mum; Saarbruecken penetration model (SB) and intact porcine tissue (IP). Each skin sample was segmented 1, 4 and 21 h after application of an 'infinite dose' of flufenamic acid. The lipophilic drug was extracted from the SC and the deeper skin layers (viable epidermis and dermis) and determined using high-performance liquid chromatography (HPLC). For each test system, an increase in the drug amount in the deeper skin layers and the acceptor fluid, respectively, was observed in combination with a decreased amount in the SC with increasing time after application. The drainage of the SC reservoir was only reflected by a linear correlation of the drug amount in the SC with the amount in the deeper skin layers in the case of IP. The absolute drug concentrations previously detected in human skin in vivo and in vitro were compared with the present data, affording the best accordance in the case of IP.

Animals↗
PubMed2004

[Penetration of microparticles into human skin].

The efficacy of the penetration of microparticles into the human skin depends on the size and the type of the formulation with which they are topically applied. Microparticles with a diameter of >1 microm barely penetrate into the human skin. They are located on the skin surface and form a film which, for instance, can be used for camouflage or protection against UV radiation in sunscreens. While the penetration of the microparticles in the lipid layers of the stratum corneum is limited, they penetrate efficiently into the hair follicles up to a depth >2 mm, providing their diameter is <1.5 microm. Thus, microparticles can be used for drug delivery into the hair follicles.

Drug Carriers↗
PubMed2004

Cloning of murine IL-22 receptor alpha 2 and comparison with its human counterpart.

We have identified the mouse and rat homologs of human interleukin-22 receptor alpha 2 (IL-22R alpha 2) and compared the localization, structure, and expression of the encoding murine and human genes. The mouse IL-22R alpha 2-encoding gene is located on chromosome 10A3 between, like in human, the genes for interferon-gamma R1 and IL-20R1. It spans a region of approximately 10 kb therefore being three times shorter than the human gene. Although the overall gene structure in both species is similar, the mouse gene lacks a counterpart to the third coding exon of the human gene known to be alternatively spliced. Like in human, mouse and rat IL-22R alpha 2 exist only as soluble receptors as deduced from the lack of transmembrane and intracellular domains encoding sequences. Quantitative expression analyses showed, analogically to the human system, a limited tissue distribution of mouse IL-22R alpha 2 mRNA. Differential modulation of IL-22R alpha 2 mRNA expression was observed upon systemic inflammation in mice in spleen, thymus, and lymph node.

Amino Acid Sequence↗
PubMed2004

Palpable arciform migratory erythema in an HIV patient, a CD8+ pseudolymphoma.

BACKGROUND: Palpable arciform migratory erythema (PAME) is characterized by large, elevated, reddish annular lesions localized on the upper trunk. As its infiltrate consists predominantly of dense infiltrates of CD4+ lymphocytes with polyclonal T-cell receptor (TCR) gene rearrangement, it has been grouped as a rare member of the T-cell pseudolymphomas. METHODS: We performed histology, immunophenotyping, and TCR-gamma gene rearrangement studies in an human immunodeficiency virus (HIV)-positive patient, CDC stage IIIB, who showed a clinically typical PAME. RESULTS: While TCR-gamma gene rearrangement studies showed a polyclonal infiltrate confirming a pseudolymphoma, 85% of skin-infiltrating lymphocytes were CD8+ T cells. CONCLUSION: PAME may also occur in HIV-positive patients with CD4+ deficiency. Our case demonstrates that regular CD4 counts and immunocompetence are not necessary for its pathogenesis.

Adult↗
PubMed2004

Polyclonal expansion of T cells with the TCR V beta type of the tumour cell in lesions of cutaneous T-cell lymphoma: evidence for possible superantigen involvement.

The involvement of superantigens in the pathology of cutaneous T-cell lymphomas (CTCL) has been suggested before, but without unequivocal evidence for superantigen activity in the patients. Seeking evidence for superantigen activity we analysed clones and microdissected single cells isolated from the epidermis of early-stage lesions of a CTCL patient for their T-cell receptor (TCR) V beta expression and TCR V gamma gene rearrangements. The vast majority of these T cells expressed the TCR V beta family type of the tumour. From their TCR gamma gene rearrangements, however, these cells were polyclonal. The tumour cell clone accounted for about 60% of these cells, about 40% were of heterogeneous origin. This dominance of a single V beta family in the polyclonally expanded dermal T-cell populations implies superantigen activity in the CTCL lesions.

Epidermis↗
PubMed2004

Biological therapies in the systemic management of psoriasis: International Consensus Conference.

Psoriasis is a chronic, immune-mediated disorder that usually requires long-term treatment for control. Approximately 25% of patients have moderate to severe disease and require phototherapy, systemic therapy or both. Despite the availability of numerous therapeutic options, the long-term management of psoriasis can be complicated by treatment-related limitations. With advances in molecular research and technology, several biological therapies are in various stages of development and approval for psoriasis. Biological therapies are designed to modulate key steps in the pathogenesis of psoriasis. Collectively, biologicals have been evaluated in thousands of patients with psoriasis and have demonstrated significant benefit with favourable safety and tolerability profiles. The limitations of current psoriasis therapies, the value of biological therapies for psoriasis, and guidance regarding the incorporation of biological therapies into clinical practice are discussed.

Age Factors↗
PubMed2004

Sunscreen application at the beach.

BACKGROUND: The sun protection factor (SPF) of sunscreens is determined after application of a standard amount. The European Cosmetic Toiletry and Perfumery Association (COLIPA) standard amount is 2 mg/cm(2). Real-life application of sunscreen is probably less than this. AIM: To determine the amount of sunscreen present on the skin of people at the beach. METHODS: Volunteers at the beach were selected randomly and were not aware of being tested for the adequacy of their sunscreen application. All volunteers had applied sunscreen. Application had been more than 30 min before testing (sometimes up to 4 h earlier). The amounts of sunscreen applied to different body sites were determined quantitatively by tape stripping. Actual amounts of sunscreen applied were compared with the COLIPA standard. Also, sunscreen containing a fluorescent dye was applied to the skin of volunteers in a laboratory setting. The distribution of sunscreen application was visualized by UVA photography in a darkened room. RESULTS: Sixty volunteers, 33 males and 27 females, aged 17-68 years (median 32 years), were recruited at the beach. Sunscreen coverage was inadequate at all body sites. Coverage at various body sites differed greatly. Most volunteers had applied 10% or less of the COLIPA standard amount to all body sites assessed. The best protected areas were the upper arm and décolleté but, even in these areas, most volunteers had only applied 10% of the COLIPA standard amount. The worst protected areas were the ears and top of the feet. The back was typically badly protected if treated by the volunteers themselves. The back was better protected if another person had applied the sunscreen. In the laboratory, the fluorescent dye-containing sunscreen showed the same pattern of sunscreen application as at the beach. CONCLUSIONS: In real life, at the beach, very little sunscreen remains present on the skin.

Journal Article↗
PubMed2003

[Follicular penetration. An important pathway for topically applied substances].

The knowledge of penetration pathways in and through the skin is a prerequisite for the development and optimization of topically applied drugs and cosmetics. Skin penetration has been assumed to occur via diffusion though the lipid domains of the stratum corneum. Recent studies show that the skin appendages, especially the hair follicles, play an important role in skin penetration processes. Topically applied substances cannot enter all follicles. We discuss the reasons for the phenomenon of open and closed hair follicles.

Administration, Cutaneous↗
PubMed2003

[Use of biologicals in psoriasis].

With a prevalence of 2-3 percent, psoriasis is one of the most common diseases in dermatology. Most patients can be treated sufficiently with topical emollients, but approximately 20 percent of all patients suffering from psoriasis need photo- and/or systemic therapies. Side effects, contraindications, insufficient clinical responses, and lack of long-term efficacy underline the need for novel and improved antipsoriatic therapies. Several biologics interfering with key steps in the immunopathogenesis of psoriasis bear the potential to meet this need with regard to treating moderate to severe psoriasis. Progress made in the understanding of the pathophysiology of psoriasis as T-cell mediated dermatosis does provide options for new, more precise therapeutic approaches. These immunological therapeutic strategies are targeted at the inhibition of T-cell activation, the depletion of activated T-lymphocytes, the inhibition of adhesion of inflammatory cells, the inhibition of effects of proinflammatory cytokines and the application of antiinflammatory cytokines. This article gives a summary of new biologicals used in the treatment of psoriasis. Clinical results received from first applications are inconclusive. Further results of the studies from phase II and phase III can be expected in the next few years, which should make it possible to achieve better assessments of the potential of these types of treatments. Some of these approaches could lead to the approval of new drugs to treat psoriasis and to enhance or replace already existing therapeutic options.

Anti-Inflammatory Agents↗