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Background: Regulated alteration of connexin expression has been shown to be integral to acute wound repair. Downregulation of the gap-junction protein connexin 43 at the wound edge has been correlated with keratinocyte and fibroblast migration, while abnormal overexpression of connexin 43 significantly perturbs healing, as shown in the streptozotocin diabetic rodent impaired healing model., Objectives: To examine the protein expression levels of connexin 43, in addition to connexins 26 and 30, in a variety of human chronic wounds., Methods: Wound-edge punch biopsies and a matched control from the arm were taken from a cohort of patients with venous leg, diabetic foot or pressure ulcers. Wound connexin expression in each patient was compared with that in a matched, nonwounded arm punch. Tissue was sectioned, stained and imaged by confocal microscopy using identical parameters per patient to permit quantification., Results: Epidermal connexin 43, connexin 26 and connexin 30, and dermal connexin 43 were discovered to be strikingly upregulated in every ulcer from all three wound types, pointing to connexin upregulation as a common feature between chronic wounds., Conclusions: This result supports efforts to target connexin 43 to promote cell migration and wound healing in chronic ulcers., (© 2015 British Association of Dermatologists.)

GnRH-secreting neurons are known to originate in the epithelium of the medial olfactory placode, whence they migrate along the axons of the terminal nerve via the forebrain and into the hypothalamus. Synaptic contact between the developing olfactory bulbs and fascicles of the vomeronasal, terminal, and olfactory nerves does not occur in Kallmann's syndrome. Consequently, there is migration arrest of GnRH cells and partial or complete failure of formation of the olfactory bulbs, resulting in severe olfactory deficit and hypogonadotropic hypogonadism. In the present study, using an immunofluorescent, double immunostaining technique and confocal laser scanning microscopy, we observed GnRH-immunoreactive neurons in the hypothalamus of a 14-week-old human fetus. However, migration of GnRH neurons was not complete, and indeed, such cells were seen to be migrating along terminal nerve fascicles beneath the cribriform plate in a 16-week-old fetus. The same immunofluorescent technique demonstrated the presence of GnRH cells in biopsies of nasal mucosa obtained from three adults with Kallmann's syndrome, one normosmic subject with hypogonadotropic hypogonadism, and a eugonadal male cadaver. These findings are consistent with two different interpretations: the nasal GnRH neurons may be vestigial, representing cells that failed to migrate during embryogenesis; alternatively, they may have been generated de novo later in life, a possibility consistent with the recognized plasticity of human postnatal olfactory neuroepithelium. They also reveal that subjects with the normosmic (i.e. non-Kallmann's) form of GnRH deficiency are able to synthesize immunologically recognizable GnRH, implying that failure of GnRH synthesis is not responsible for this type of hypogonadotropic hypogonadism.

Ulcerative colitis (UC) has a proposed autoimmune pathogenesis. A 40-kD antigen (P40) has been isolated from UC colon, bound to immunoglobulin. Tropomyosin has been reported as the target antigen of a MoAb (7E12H12) raised against P40. We set out to investigate whether tropomyosin is the major antigenic determinant for 7E12H12. Formalin-fixed, paraffin-processed and cryostat sections of fresh frozen colon from patients with UC, Crohn's disease and normals, were immunostained with 7E12H12 and commercial anti-tropomyosin antibodies. In addition, the immunoreactivity of 7E12H12 with cytoskeletal components was examined on human endothelial cells (HUVEC) using anti-tropomyosin as a positive control. Con-focal microscopy was used to determine the subcellular localization of signal. An extract of total colonic protein from UC colon was prepared. Using a combination of Western and immunoblotting (dot-blots), the immunoreactivities of both tropomyosin (porcine and chicken) and colon protein extract with either 7E12H12 or commercial anti-tropomyosin were examined. Immunocytochemically, 7E12H12 localized to the apical and basolateral regions of plasma membrane, and to the supranuclear cytoplasm in colonic epithelium. Using anti-tropomyosin antibody it was not possible to identify the cytoskeleton in colonic epithelium. Cytoskeletal components were identifiable in HUVEC cultures with anti-tropomyosin antibody but not with 7E12H12. P40 antigen was identified in the colon protein extract by immunoblotting with 7E12H12. There was clear immunoreactivity between anti-tropomyosin antibody and both chicken and porcine tropomyosin, and the colon protein extract. 7E12H12 did not bind to either chicken or porcine tropomyosin in appropriately controlled systems. We conclude that the pattern of immunostaining with 7E12H12 is not cytoskeletal, and there is no reactivity in immunoblots, between tropomyosin and 7E12H12. Tropomyosin is not the major target antigen of this antibody in ulcerative colitis.