First Association of Interleukin 12 Receptor Beta 1 Deficiency with Sjögren's Syndrome.

Introduction: Interleukin 12 receptor beta 1 (IL12Rβ1) deficiency is a primary immunodeficiency resulting mainly in susceptibility to opportunistic infection by non-tuberculous, environmental mycobacteria and severe infection caused by spp. Till now, less than 300 patients with IL12Rβ1 deficiency have been reported. Among them, only three have been described to develop autoimmunity.

S1-Leitlinie Lipödem.

Die vorliegende überarbeitete Leitlinie zum Lipödem wurde unter der Federführung der Deutschen Gesellschaft für Phlebologie (DGP) erstellt und finanziert. Die Inhalte beruhen auf einer systematischen Literaturrecherche und dem Konsens von acht medizinischen Fachgesellschaften und Berufsverbänden. Die Leitlinie beinhaltet Empfehlungen zu Diagnostik und Therapie des Lipödems.

S1 guidelines: Lipedema.

The present, revised guidelines on lipedema were developed under the auspices of and funded by the German Society of Phlebology (DGP). The recommendations are based on a systematic literature search and the consensus of eight medical societies and working groups. The guidelines contain recommendations with respect to diagnosis and management of lipedema.

Characterisation of Prognosis and Invasion of Cutaneous Squamous Cell Carcinoma by Podoplanin and E-Cadherin Expression.

Background: Around 5% of all cutaneous squamous cell carcinoma (cSCC) metastasise. Metastases usually locate in regional skin and lymph nodes, suggesting collective cancer invasion. The cellular level of tumour invasion and prognostic parameters remain to be characterised.

Allele frequencies of BRAFV600 mutations in primary melanomas and matched metastases and their relevance for BRAF inhibitor therapy in metastatic melanoma.

Background: The detection of BRAFV600 mutations in patients with metastatic melanoma is important because of the availability of BRAF inhibitor therapy. However, the clinical relevance of the frequency of BRAFV600 mutant alleles is unclear.

Patients And Methods: Allele frequencies of BRAFV600 mutations were analyzed by ultra-deep next-generation sequencing in formalin-fixed, paraffin-embedded melanoma tissue (75 primary melanomas and 88 matched metastases).

No human virus sequences detected by next-generation sequencing in benign verrucous skin tumors occurring in BRAF-inhibitor-treated patients.

Patients treated with BRAF inhibitors (e.g. vemurafenib), a novel targeted therapy for advanced melanoma harbouring certain BRAF mutations, develop numerous adverse cutaneous side effects, including skin tumors such as squamous cell carcinoma or non-malignant verruciform keratinocyte proliferations, termed 'BRAF-inhibitor-associated verrucous keratosis (BAVK) lesions'.

Role of kindlin-2 in fibroblast functions: implications for wound healing.

Kindlins are a protein family that regulates cell-matrix interactions. Although kindlin-2 is known to be essential for the early developmental processes, its role in the homeostasis of adult tissues has remained elusive. In this study, we used new domain-specific antibodies and small interfering RNA technology to uncover physiological functions of kindlin-2 in human dermal fibroblasts in vitro and in adult skin in situ.

Collagen-based cell migration models in vitro and in vivo.

Fibrillar collagen is the most abundant extracellular matrix (ECM) constituent which maintains the structure of most interstitial tissues and organs, including skin, gut, and breast. Density and spatial alignments of the three-dimensional (3D) collagen architecture define mechanical tissue properties, i.e.

Hyperforin and aristoforin inhibit lymphatic endothelial cell proliferation in vitro and suppress tumor-induced lymphangiogenesis in vivo.

The phloroglucinol derivative hyperforin, a major bioactive constituent of St. John's wort, is increasingly recognized as being able to regulate a variety of pathobiological processes and, thus, to possess potential therapeutic properties. In the context of cancer, hyperforin induces the apoptosis of cancer cells, inhibits angiogenesis and suppresses metastasis formation.

Anatomy of the subcutaneous lymph vascular network of the human leg in relation to the great saphenous vein.

The anatomical relationship between lymphatic collectors and veins is of clinical importance for preventing lymphedema secondary to lymphatic collector injury during surgical procedures. To identify areas at risk during surgical interventions, we performed an anatomical study of human legs. The lymphatic collectors of 42 legs of human cadavers were injected with Berlin Blue solution or contrast medium.

HGF and MET mutations in primary and secondary lymphedema.

Background: Lymphedema is the abnormal accumulation of protein-rich fluid in the interstitial space. Primary lymphedema is a rare genetic condition with both autosomal dominant and autosomal recessive modes of inheritance. Three genes, FLT4 (VEGFR3), FOXC2, and SOX18 cause varying forms of primary lymphedema.

Photothermolysis of blood vessels using indocyanine green and pulsed diode laser irradiation in the dorsal skinfold chamber model.

Background And Objective: For the treatment of vascular lesions, the use of laser light absorbed by the endogenous chromophore hemoglobin may still be improved.

Materials And Methods: Laser treatment (lambda(em) = 805 nm; fluence rate: 106 kW/cm2; fluence: 3.2 J/cm2 (3 milliseconds)), of blood vessels directly after i.

Photodynamic therapy with 5-aminolevulinic acid induces distinct microcirculatory effects following systemic or topical application.

In photodynamic therapy (PDT) the photosensitiser 5-aminolaevulinic acid (ALA) can be used by systemic or topical application. Previous experiments showed that the photodynamic effects might not be mediated solely by porphyrins localized in the parenchyma, but also by porphyrins in the microvasculature. Therefore, the microcirculatory effects of PDT following systemic versus topical application of ALA have been investigated.

In vivo phosphorescence imaging of pO2 using planar oxygen sensors.

Objective: Oxygen-dependent quenching of luminescence of metal porphyrin complexes has been used to image the pO(2) distribution over tumor and normal tissue.

Methods: An experimental setup is described using a platinum(II)-octaethyl-porphyrin immobilized in a polystyrene matrix as transparent planar sensor.

Results: Sensitivity over a broad range is high at low pO(2) values (+/- 0.

Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors.

The mucin-type glycoprotein podoplanin is specifically expressed by lymphatic but not blood vascular endothelial cells in culture and in tumor-associated lymphangiogenesis, and podoplanin deficiency results in congenital lymphedema and impaired lymphatic vascular patterning. However, research into the biological importance of podoplanin has been hampered by the lack of a generally available antibody against the human protein, and its expression in normal tissues and in human malignancies has remained unclear. We generated a human podoplanin-Fc fusion protein and found that the commercially available mouse monoclonal antibody D2-40 specifically recognized human podoplanin, as assessed by enzyme-linked immunosorbent assay and Western blot analyses.

Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia.

Vascular endothelial growth factor-A (VEGF-A) expression is up-regulated in several inflammatory diseases including psoriasis, delayed-type hypersensitivity (DTH) reactions, and rheumatoid arthritis. To directly characterize the biologic function of VEGF-A in inflammation, we evaluated experimental DTH reactions induced in the ear skin of transgenic mice that overexpress VEGF-A specifically in the epidermis. VEGF-A transgenic mice underwent a significantly increased inflammatory response that persisted for more than 1 month, whereas inflammation returned to baseline levels within 7 days in wild-type mice.