Background and Purpose-Bone marrow cell (BMC)-based therapies, either the transplantation of exogenous cells or stimulation of endogenous cells by growth factors like the granulocyte colony-stimulating factor (G-CSF), are considered a promising means of treating stroke. In contrast to large preclinical evidence, however, a recent clinical stroke trial on G-CSF was neutral. We, therefore, aimed to investigate possible synergistic effects of co-administration of G-CSF and BMCs after experimental stroke in mice to enhance the efficacy compared with single treatments. Methods-We used an animal model for experimental stroke as paradigm to study possible synergistic effects of co-administration of G-CSF and BMCs on the functional outcome and the pathophysiological mechanism. Results-G-CSF treatment alone led to an improved functional outcome, a reduced infarct volume, increased blood vessel stabilization, and decreased overall inflammation. Surprisingly, the combination of G-CSF and BMCs abrogated G-CSFs' beneficial effects and resulted in increased hemorrhagic infarct transformation, altered blood-brain barrier, excessive astrogliosis, and altered immune cell polarization. These increased rates of infarct bleeding were mainly mediated by elevated matrix metalloproteinase-9-mediated blood-brain barrier breakdown in G-CSF-and BMCs-treated animals combined with an increased number of dilated and thus likely more fragile vessels in the subacute phase after cerebral ischemia. Conclusions-Our results provide new insights into both BMC-based therapies and immune cell biology and help to understand potential adverse and unexpected side effects.
ZusammenfassungKutane Lymphome präsentieren sich klinisch und histologisch oftmals ungewöhnlich und stellen nicht selten eine diagnostische Herausforderung für den Dermatologen dar. In dieser Arbeit werden die vielgestaltigen Präsentationsformen der Mycosis fungoides und anderer kutaner Lymphome anhand von Fallbeispielen aus der Würzburger Spezialsprechstunde für kutane Lymphome vorgestellt und ein Überblick über die Verwechslungsmöglichkeiten mit anderen Dermatosen gegeben.
Summary
Scleroderma is a heterogeneous group of fibrosing connective tissue disorders of unknown etiology. Morphea is a localized form of scleroderma that occasionally leads to chronic erosions and ulcerations of the skin. Fibrosis, inflammation and chronic ulcerations may eventually promote skin neoplasms; morphea is therefore a rare but established risk factor for cutaneous squamous cell carcinoma (cSCC). We present a review of 16 scleroderma patients: 15 case reports from the literature (identified by a PubMed search) and one case from our clinic of a patient who had developed cSCC, and we discuss potential underlying mechanisms. Statistical analysis revealed that the lower extremities were the body site most commonly affected by cSCC in these scleroderma patients. The mean time interval between the onset of scleroderma and the development of cSCC was ten to twenty years. In patients with morphea, we recommend checking for skin tumors during follow‐up examinations as well as a careful risk‐benefit analysis when considering the application of immunosuppressants or phototherapy in view of their potential carcinogenic side effects.
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