Cell-Type-Specific Differentiation and Molecular Profiles in Skin Transplantation: Implication of Medical Approach for Genetic Skin Diseases

Skin is highly accessible and valuable organ, which holds promise to accelerate the understanding of future medical innovation in association with skin transplantation, engineering, and wound healing. In skin transplantation biology, multistage and multifocal damages occur in both grafted donor and perilesional host skin and need to be repaired properly for the engraftment and maintenance of characteristic skin architecture. These local events are more unlikely to be regulated by the host immunity, because human skin transplantation has accomplished the donor skin engraftment onto the immunocompromised or immunosuppressive animals. Recent studies have emerged the importance of α-smooth muscle actin- (SMA-) positive myofibroblasts, via stage- and cell-specific contribution of TGFβ, PDGF, ET-1, CCN-2 signalling pathways, and mastocyte-derived mediators (e.g., histamine and tryptase), for the functional reorganisation of the grafted skin. Moreover, particular cell lineages from bone marrow (BM) cells have been shown to harbour the diferentiation capacity into multiple skin cell phenotypes, including epidermal keratinocytes and dermal endothelial cells and pericytes, undercontrolled by chemokines or cytokines. From a dermatological viewpoint, we review the recent update of cell-type- and molecular-specific action associated with reconstitution of the grafted skin and also focus on the novel application of BM transplantation medicine in genetic skin diseases

Novel Point Mutations in the Steroid Sulfatase Gene in Patients with X-Linked Ichthyosis: Transfection Analysis Using the Mutated Genes

X-linked ichthyosis is caused by steroid sulfatase deficiency which results from abnormalities in its coding gene. The majority of X-linked ichthyosis patients (≈90%) have complete or partial deletions of the steroid sulfatase gene. In this study, we examined the mutations of the steroid sulfatase gene in two unrelated X-linked ichthyosis patients without complete deletion of the gene. Polymerase chain reaction–single-strand conformation polymorphism and direct sequencing analyses showed that each patient has a different single base pair substitution within exon 8 encoding the C-terminal half of the steroid sulfatase polypeptide. Both mutations resulted in the transversion of functional amino acids: a G→C substitution at nucleotide 1344, causing a predicted change of a glycine to an arginine, and a C→T substitution at nucleotide 1371, causing a change from a glutamine to a stop codon. In vitro steroid sulfatase cDNA expression using site-directed mutagenesis revealed that these mutations are in fact pathogenic and reflect the levels of steroid sulfatase enzyme activities in each of the X-linked ichthyosis patients

Skin Prick Test with Self-Saliva in Patients with Oral Aphthoses: A New Diagnostic Pathergy for Behcet’s Disease and Recurrent Aphthosis

There may be some difficulties to differentiate Behcet’s disease (BD), recurrent aphthosis (RA), and herpetic aphthous ulceration, from other mimicking oral disorders. Despite of unexpected sensitivity and responsiveness, the skin pathergy test regarding a non-specific hypersensitivity has long been thought as one of auxiliary diagnostic benefits for BD

Role of IL-12B Promoter Polymorphism in Adamantiades–Behcet's Disease Susceptibility: An Involvement of Th1 Immunoreactivity against Streptococcus Sanguinis Antigen

Adamantiades–Behcet's disease (ABD) is a chronic inflammatory multisystem disorder. Although the precise etiology is unclear, high prevalence of human leukocyte antigen (HLA)-B51 predisposition and predominantly involved T-helper type 1 cells (Th1)-type proinflammatory cytokines and extrinsic Streptococcal infection suggest a substantial association with an immunogenetic basis and strengthens the hypothesis that IL-12, a potent inducer of Th-1 immune reaction, is a putative candidate in its pathogenesis. These clinicopathological findings led us to examine interleukin 12 p40 (IL-12B) promoter polymorphism, for which the 4-base pair (bp) heterozygous insertion has been shown to affect the gene transcription and subsequent protein production. We analyzed IL-12B promoter genotypes in 194 Japanese subjects (92 with ABD and 102 normal controls) by PCR-based restriction enzyme digestion. The frequency of the insertion heterozygosity was significantly higher in patients than in controls (49/92, 53.3% vs 39/102, 38.2%, respectively). Comparing these with HLA haplotype data, this trend was more significant in HLA-B51-negative patients (29/42, 69.0% vs 20/50, 40.0%; P=0.005). As assessed by semiquantitative reverse transcription-PCR and ELISA, stimulation with Streptococcal antigens specifically increased expression of IL-12 p40 mRNA and protein, in conjunction with IL-12 p70 induction, in peripheral blood mononuclear cells from heterozygous patients. Our results provide evidence for anti-bacterial host response toward Th1-immunity mediated by IL-12 in patients with ABD, and the possible insight into the genetic susceptibility that is independent of HLA background

Low temperature formation of low resistivity W contact with ultra thin mixed layer on molecular layer epitaxially-grown GaAs

Proceedings of the IEEE 24th international symposium on compound semiconductors, San diego, California, 8-11 Semptember 199

Behçet's Disease (Adamantiades-Behçet's Disease)

Adamantiades-Behçet's disease (ABD) is characterized by starting with oral aphthous ulceration and developing of the systemic involvements. The pathogenesis of ABD is closely correlated with the genetic factors and the triggering factors which acquire delayed-type hypersensitivity reaction against oral streptococci mediated by IL-12 cytokine family. HLA-B51 is associated in more than 60% of the patients and its restricted CD8+ T cell response is clearly correlated with the target tissues. Bes-1 gene encoded partial S. sanguinis genome which is highly homologous with retinal protein, and 65 kD heat shock protein (Hsp-65) released from streptococci is playing an important role with human Hsp-60 in the pathogenesis of ABD. Although Hsp-65/60 has homologies with the respective T cell epitope, it stimulates peripheral blood mononuclear cells (PBMCs) from ABD patients. On the other hand, some peptides of Hsp-65 were found to reduce IL-8 and IL-12 production from PBMCs of ABD patients in active stage

Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus

Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients’ sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus