The dimensions and characteristics of the subepidermal nerve plexus in human skin--terminal Schwann cells constitute a substantial cell population within the superficial dermis.

Background: The skin constitutes the largest sensorial organ. Its nervous system consists of different types of afferent nerve fibers which spread out immediately beneath the skin surface to sense temperature, touch and pain.

Objective: Our aim was to investigate the dimension and topographic relationship of the different nerve fibers of the subepidermal nerve plexus in human hairy skin and to analyze numbers and marker expression of terminal Schwann cells.

Embryonic stem cell factors undifferentiated transcription factor-1 (UFT-1) and reduced expression protein-1 (REX-1) are widely expressed in human skin and may be involved in cutaneous differentiation but not in stem cell fate determination.

Undifferentiated transcription factor-1 (UTF-1) and reduced expression protein-1 (REX-1) are used as markers for the undifferentiated state of pluripotent stem cells. Because no highly specific cytochemical marker for epidermal stem cells has yet been identified, we investigated the expression pattern of these markers in human epidermis and skin tumours by immunohistochemistry and in keratinocyte cell cultures. Both presumed stem cell markers were widely expressed in the epidermis and skin appendages.

Expression of VEGF-A/C, VEGF-R2, PDGF-alpha/beta, c-kit, EGFR, Her-2/Neu, Mcl-1 and Bmi-1 in Merkel cell carcinoma.

Merkel cell carcinoma is a rare but very aggressive tumor of the skin. With current treatment options, Merkel cell carcinoma is associated with a high incidence of recurrence and metastasis. Targeted anticancer therapies such as receptor tyrosine kinase inhibitors and antisense oligonucleotides have been found to be a promising new type of treatment for various types of cancer.

Rarefaction of the peripheral nerve network in diabetic patients is associated with a pronounced reduction of terminal Schwann cells.

Objective: Peripheral neuropathy is the most frequent neurological complication in diabetic patients. The diagnosis is established by both clinical neurological examination and demonstration of reduced epidermal nerve fibers in skin biopsies (1). Whereas the decrease of free nerve endings has been extensively studied in diabetic patients (2,3), no data are available on possible changes of terminal Schwann cells.

Expression of BMI-1 in normal skin and inflammatory and neoplastic skin lesions.

Background: BMI-1 is involved in the maintenance of stem cells and functions as an oncogene in both lymphomas and solid carcinomas, acting by downregulation of p16ink4a. We have investigated the expression profile of BMI-1 in normal and inflamed skin as well as in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs).

Methods: BMI-1 expression was determined by immunohistochemistry and immunofluorescence, and evaluated semiquantitatively.

The touch dome in human skin is supplied by different types of nerve fibers.

Receptor end organs and free-nerve endings in the skin are the peripheral sentinels of the sensorial nervous system encoding for touch, temperature, and pain. Using a novel approach to analyze the outermost nerves of the skin, we visualized for the first time the distinct microanatomical structure of the touch dome of human hairy skin. The dermal nerve fibers of this slowly adapting type 1 mechanoreceptor were embedded in dermal protrusions that could be readily discerned by Laminin-5 staining.

Sheet preparations expose the dermal nerve plexus of human skin and render the dermal nerve end organ accessible to extensive analysis.

Since vertical tissue sections used for the study of the human cutaneous nervous system inherently allow visualization of only a small part of the mainly horizontally oriented cutaneous nerves, we searched for possibilities to extend this view. We now propose a method based on the immuno-staining of dermal sheet preparations for subsequent analysis by electron-, light- or laser scanning microscopy. Dermal sheet preparations for the first time allowed the imaging of the complex structure of the nerve end organ over several cm2, and facilitated viewing of its topological relationship to other tissue components.

Inhibition of human neutrophil chemotaxis toward interleukin 8 with six clinical antithrombin concentrates in vitro.

Objective: Antithrombin exerts direct effects on neutrophils by inhibiting chemokine-induced migration. This study examined the potency of different pharmaceutical antithrombin preparations in inhibiting neutrophil chemotaxis toward interleukin 8.

Methods: Cell migration was tested by the leading front assay in modified Boyden microchemotaxis chambers bearing nitrocellulose filters.

Inhibition of plasma-dependent monocyte chemokinesis and cytokine-triggered endothelial activation for neutrophil transmigration by administration of clopidogrel in man.

Mediators released by spontaneously activated platelets may contribute to alterations in endothelial and leukocyte dysfunctions. We investigated the roles of clopidogrel and aspirin in ex vivo endothelial activation for interactions with leukocytes. Eight healthy volunteers received clopidogrel or aspirin for 8 days.

Syndecan-4 mediates antithrombin-induced chemotaxis of human peripheral blood lymphocytes and monocytes.

Antithrombin inhibits chemokine-induced migration of neutrophils by activating heparan sulfate proteoglycan-dependent signaling. Whether antithrombin affects migration of other types of leukocytes is not known. We investigated the effects of antithrombin on spontaneous and chemokine-triggered migration of lymphocytes and monocytes from human peripheral blood in modified Boyden chamber micropore filter assays.