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Biomedical subjects

S Grabbe

Publications and source records attributed to S Grabbe.

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

[Comparison of the minimal erythema dose for narrowband UV-B and broad spectrum UV-B using a new UV hand-held device].

BACKGROUND: Phototherapy requires an individually adapted therapeutic regime that is based upon the minimal erythema dose for each patient. Whereas this is well established for UV-B broadband, so far no standardized equipment existed that allowed for determination of the MED for UV-B 311 nm narrowband irradiation. Thus, the starting dose for UV-B 311 nm is usually adjusted to the clinical skin type or the MED for broad-spectrum UV-B irradiation. PATIENTS AND METHODS: We determined the MED for UV-B 311 nm in a cohort of 110 healthy test persons with a newly constructed hand-held UV-light source and compared it to UV-B broadband MED. RESULTS: For UV-B broadband, the MEDs ranged from 46.2 to 210.9 mJ/cm(2) with an average value of 108.45 mJ/cm(2). For the MED of narrowband UV-B 311 nm, the values ranged from 300.9 to 1.386.0 mJ/cm(2) with an average value of 838.88 mJ/cm(2). Concerning the factor of the MED UV-B broad-spectrum related to MED UV-B 311 nm narrowband, values from 4.01 to 13.68 with a average value of 7.91 resulted. No significant differences could be detected for the MED of UV-B broad-spectrum and narrowband in correlation to age, sex or clinical skin type. CONCLUSION: Our data emphasize the presence of extensive inter-individual differences in the MED of both UV-B-spectra and point to the necessity to test patients before the first irradiation.

Adolescent↗
PubMed2005

[Antimicrobial peptides. A perspective for the treatment of chronic wounds?].

Human antimicrobial peptides play a substantial role in the immune response to various dermatological diseases, such as acne, atopic dermatitis and psoriasis vulgaris, and even mucosal HIV-protection is mediated inter alia by antimicrobial peptides. In wound healing, the antimicrobial and immune-modulating properties of, in particular, human defensins and cathelicidins can affect important controlling factors. For example, the interaction between different antimicrobial peptides and growth factors supports neoangiogenesis. Although further clinical investigations are necessary to identify the exact effects of antimicrobial peptides in chronic wounds, such peptides could be a promising therapeutic option in the near future for the treatment of patients with chronic wounds by promoting endogen expression or exogenous supplementation.

Anti-Infective Agents↗
PubMed2005

[Clinical variants of acne].

Acne is a very common dermatosis with characteristic clinical features. It is a polymorphic disease. The clinical expression ranges from non-inflammatory closed and open comedones to inflammatory papules, pustules, and nodules. Most patients have a mixture of non-inflammatory and inflammatory lesions, although some have predominantly one or the other. Acne varies in severity from a very distressing, socially disabling disorder to a state that has been regarded as physiological by some authors. The most severe forms of acne are acne fulminans and acne inversa. Although acne may occur in all age groups, it is most prevalent during adolescence. It is not known why acne subsides in most patients but persists into adulthood in some. Certain medications may be associated with provocation, perpetuation, or exacerbation of pre-existing acne or with acneiform eruptions. Acne-like disorders include rosacea, pseudofolliculitis barbae, and other conditions that share clinical features with acne.

Acne Vulgaris↗
PubMed2005

[Value of sentinel node biopsy considering melanoma management as an example].

Sentinel lymph node biopsy has replaced elective lymph node dissection in the management of melanoma. It provides an exact staging method of the regional lymph basin and is associated with low morbidity. Patients who are found to have a positive sentinel lymph node can selectively undergo regional lymph node dissection. Sentinel lymph node biopsy also provides the means to stratify patients into homogeneous groups for adjuvant therapies. Sentinel lymph node involvement is regarded as an independent prognostic factor. The therapeutic value of subsequent surgical and medical therapies in patients with positive sentinel nodes is currently being investigated in clinical trials.

Humans↗
PubMed2004

Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices.

Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and allergic or bacterial proteases. This receptor is expressed by various cells and seems to be crucially involved during inflammation and the immune response. As previously reported, human neutrophils express functional PAR2. However, the precise physiological role of PAR2 on human neutrophils and its implication in human diseases remain unclear. We demonstrate that PAR2 agonist-stimulated human neutrophils show significantly enhanced migration in 3-D collagen lattices. PAR2 agonist stimulation also induced down-regulation of L-selectin display and up-regulation of membrane-activated complex-1 very late antigen-4 integrin expression on the neutrophil cell surface. Moreover, PAR2 stimulation results in an increased secretion of the cytokines interleukin (IL)-1beta, IL-8, and IL-6 by human neutrophils. These data indicate that PAR2 plays an important role in human neutrophil activation and may affect key neutrophil functions by regulating cell motility in the extracellular matrix, selectin shedding, and up-regulation of integrin expression and by stimulating the secretion of inflammatory mediators. Thus, PAR2 may represent a potential therapeutic target for the treatment of diseases involving activated neutrophils.

Calcium↗
PubMed2004

[Imiquimod, pegylated interferon-alpha-2b and interleukin-2 in the treatment of cutaneous melanoma metastases].

The immune system plays an important role in the defense against malignant melanoma. Interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) are therapeutically used for unspecific stimulation of the immune system. After intralesional injections of these cytokines into cutaneous melanoma metastases, regression has been observed. In view of its immunomodulating effects, imiquimod appears as an additional promising therapeutic option for treatment of malignant tumors. In a case report, we present combined therapy with intralesional IL-2, pegylated IFN-alpha-2b and topical imiquimod 5% cream for disseminated cutaneous metastatic malignant melanoma stage IIIa. This therapy achieved an almost complete remission. In a treatment period of eight months, side effects remained tolerable. Histologically, both fibrosis and inflammation were found in the regressing lesions. After the end of therapy, no disease progression occurred during 11 months follow-up.

Adjuvants, Immunologic↗
PubMed2002

[Persistent inflammatory reaction at the injection site of Il-2 with lymphoma-like inflammatory infiltrates].

Interleukin-2 (Il-2) is widely used for treatment of carcinomas, leukemia, and melanoma. Adverse drug effects of Il-2 include various systemic and generalized cutaneous drug reactions. In the following we report on a persistent inflammatory reaction at the injection site of Il-2. A patient received chemoimmuno-therapy for treatment of metastasizing melanoma, including subcutaneous application of recombinant interleukin-2 (Proleukin((R))). Within a few days reddish nodules developed at the injection sites that persisted after cessation of Il-2 injections for two years until final lethal outcome. Histologic examination revealed a lobular panniculitis expressing atypical lymphocytes and multinucleated histiocytes.

Aged↗
PubMed2002

Trypanosoma cruzi heat-shock protein-70 kDa,alone or fused to the parasite KMP11 antigen, induces functional maturation of murine dendritic cells.

We analyse the effect of Trypanosoma cruzi heat-shock protein-70 (HSP70) on the maturation of murine dendritic cells (DC)generated from bone marrow precursor cells. The results obtained show that HSP70, both alone and fused to the KMP11 antigen, as well as a HSP70 fragment, is capable of maturing murine DC. Mature DC have enhanced expression of IL12, TNF-alpha cytokines, costimulation molecules and activation markers, showing a clear increase in the allostimulatory capacity. These findings suggest that T. cruzi HSP70 may be a very useful vehicle for developing DC-based immunoprophylaxis and therapy against infections.

Animals↗
PubMed2001

Two-step negative enrichment of CD4+ and CD8+ T cells from murine spleen via nylon wool adherence and an optimized antibody cocktail.

We developed a method to highly purify CD4+ and CD8+ T cells from murine spleen by negative enrichment strategy. Single-cell suspensions of spleen cells were depleted from erythrocytes by ammonium chloride-mediated lysis. The obtained cell suspension contained approximately 28% CD4+ cells and 14% CD8+ cells. Passing of these cells over a nylon wool column removed up to 75% of all cells, leading to a suspension containing approximately 50% CD4+ and 23% CD8+ cells. These cells were further purified by a single immunomagnetic depletion step using a panel of eight antibodies in combination with MACS magnetic beads and an autoMACS machine. After purification, cells were viable and mostly non-activated based on the expression of activation markers and did not or only minimally respond to polyclonal stimuli such as soluble anti-CD3 antibodies or Concanavalin A. With this method, 19-38% of all CD4 cells and 10-29% of all CD8 cells in a spleen cell suspension were recovered at the mentioned purity. The whole procedure is fast (<4 h of preparation), simple and cost effective, as all antibodies and the magnetic beads have been titrated to the minimal concentration needed for purification. The method is highly reproducible, routinely leading to CD4+ cells with >97% purity (range 97.4-99%) and CD8+ cells with >96% purity (range 95.6-96.7%). The described protocol should facilitate studies aiming at the physiology of "untouched" murine T cells.

Animals↗
PubMed2001

IL-12 prevents the inhibitory effects of cis-urocanic acid on tumor antigen presentation by Langerhans cells: implications for photocarcinogenesis.

UV radiation induces skin cancer primarily by its DNA-damaging properties, but also by its capacity to suppress the immune system. The photoisomer of urocanic acid (UCA), cis-UCA, is an important mediator of UV-induced immunosuppression and is involved in the inhibition of tumor immunity. The immunomodulatory cytokine IL-12 is known to counteract many of the immunosuppressive effects of UV radiation, including UV-induced immune tolerance. In this study, we addressed whether IL-12 also reverts the immunosuppressive activities of cis-UCA. Cis-UCA inhibits the ability of Langerhans cells to present tumor Ags for primary and secondary tumor immune responses. IL-12 treatment completely prevented the suppression by cis-UCA. IL-12 also protected mice from cis-UCA-induced suppression of contact hypersensitivity responses. To study the effects of cis-UCA on Ag-processing and Ag-presenting function in vitro, Langerhans cells were treated with UCA isomers and incubated with OVA or OVA peptide(323-339) before exposure to OVA-specific transgenic T cells. Cis-, but not trans-UCA suppressed Ag presentation, which was completely reversed upon addition of IL-12. Since these findings suggest that cis-UCA may play an important role in photocarcinogenesis by inhibiting a tumor immune response, mice were chronically UVB irradiated to induce skin cancer. Whereas all mice in the control groups developed tumors, mice treated with a mAb with specificity for cis-UCA showed a significantly reduced tumor incidence. These data strongly indicate the importance of cis-UCA during photocarcinogenesis and support the concept of counteracting cis-UCA as an alternative strategy to prevent UV-induced skin cancer, possibly via the application of IL-12.

Animals↗
PubMed2001

Overexpression of CD40 ligand in murine epidermis results in chronic skin inflammation and systemic autoimmunity.

CD40-CD40 ligand (L) interactions play a pivotal role in immune-mediated inflammatory responses via the activation of antigen-presenting cells (APCs). To investigate the effects of continuous activation of resident tissue APCs, in this case the Langerhans cells (LCs) of the skin, CD40L expression was targeted to the basal keratinocytes of the epidermis of mice using the keratin-14 promoter. Approximately 80% of the transgenic (Tg) mice spontaneously developed dermatitis on the ears, face, tail, and/or paws. Compared with littermates, Tgs had a >90% decrease in epidermal LCs yet increased numbers within the dermis suggestive of enhanced emigration of CD40-activated LCs. Tgs also displayed massive regional lymphadenopathy with increased numbers of dendritic cells and B cells. Moreover, a decrease in IgM and an increase in IgG1/IgG2a/IgG2b/IgE serum concentrations was detectable. Screening for autoantibodies revealed the presence of antinuclear antibodies and anti-dsDNA antibodies implicative of systemic autoimmunity. Accordingly, renal Ig deposits, proteinuria, and lung fibrosis were observed. Adoptive transfer of T cells from Tgs to nonTg recipients evoked the development of skin lesions similar to those found in the Tgs. Dermatitis also developed in B cell-deficient CD40L Tg mice. These findings suggest that in situ activation of LCs by CD40L in the skin not only leads to chronic inflammatory dermatitis but also to systemic mixed-connective-tissue-like autoimmune disorders, possibly by breaking immune tolerance against the skin.

Animals↗