TGFß Induces a SAMHD1-Independent Post-Entry Restriction to HIV-1 Infection of Human Epithelial Langerhans Cells.

Sterile alpha motif (SAM) and histidine-aspartic (HD) domains protein 1 (SAMHD1) was previously identified as a critical post-entry restriction factor to HIV-1 infection in myeloid dendritic cells. Here we show that SAMHD1 is also expressed in epidermis-isolated Langerhans cells (LC), but degradation of SAMHD1 does not rescue HIV-1 or vesicular stomatitis virus G-pseudotyped lentivectors infection in LC. Strikingly, using Langerhans cells model systems (mutz-3-derived LC, monocyte-derived LC [MDLC], and freshly isolated epidermal LC), we characterize previously unreported post-entry restriction activity to HIV-1 in these cells, which acts at HIV-1 reverse transcription, but remains independent of restriction factors SAMHD1 and myxovirus resistance 2 (MX2). We demonstrate that transforming growth factor-ß signaling confers this potent HIV-1 restriction in MDLC during their differentiation and blocking of mothers against decapentaplegic homolog 2 (SMAD2) signaling in MDLC restores cells' infectivity. Interestingly, maturation of MDLC with a toll-like receptor 2 agonist or transforming growth factor-α significantly increases cells' susceptibility to HIV-1 infection, which may explain why HIV-1 acquisition is increased during coinfection with sexually transmitted infections. In conclusion, we report a SAMHD1-independent post-entry restriction in MDLC and LC isolated from epidermis, which inhibits HIV-1 replication. A better understanding of HIV-1 restriction and propagation from LC to CD4(+) T cells may help in the development of new microbicides or vaccines to curb HIV-1 infection at its earliest stages during mucosal transmission.

Polypropylene Sulfide Nanoparticle p24 Vaccine Promotes Dendritic Cell-Mediated Specific Immune Responses against HIV-1.

Delivery of vaccine formulations into the dermis using antigen-coated microneedle patches is a promising and safe approach because of efficient antigen delivery and safety. We evaluated an intradermal vaccine using HIV-1 p24 Gag peptide-conjugated polypropylene sulfide nanoparticles to induce immunity against HIV-1. This peptide-conjugated polypropylene sulfide nanoparticle formulation did not accelerate the maturation of blood- or skin-derived subsets of dendritic cells, either generated in vitro or purified ex vivo, despite efficient uptake in the absence of adjuvant. Moreover, dendritic cell-mediated capture of particulate antigen in this form induced potent HIV-1-specific CD4(+) T-cell responses, as well as B-cell-mediated antibody production. Nanoparticle-based intradermal antigen delivery may therefore provide a new option in the global effort to develop an effective vaccine against HIV-1.

Surgery results in complete cure of Lambert-Eaton myasthenic syndrome in a patient with metastatic Merkel cell carcinoma.

Lambert-Eaton myasthenic syndrome is a paraneoplastic phenomenon associated with neuroendocrine tumours, most frequently small cell lung carcinoma. Merkel cell carcinoma is a rare cause of Lambert-Eaton myasthenic syndrome. A 70-year old gentleman was referred with metastatic axillary nodal disease from a previously resected Merkel cell carcinoma of the left arm. Pre-operatively, the patient was wheelchair-bound from Lambert-Eaton myasthenic syndrome. Level I-III left axillary node clearance was performed and within 6 months, he had experienced full recovery of muscle power and mobility. We describe a case of complete cure of Lambert-Eaton myasthenic syndrome following axillary nodal clearance in a patient with metastatic Merkel cell carcinoma.

The birth of plastic surgery: the story of nasal reconstruction from the Edwin Smith Papyrus to the twenty-first century.

BACKGROUND: The nose is the central and most prominent feature on the human face; and on its shape, size, and appearance depends the relative facial beauty of the person. The objective of this article was to give a succinct and interesting account of the development of nasal reconstruction from antiquity to the present day. METHODS: The authors present the story of nasal reconstruction, including those contributions not often cited in the English literature using articles sourced from MEDLINE, ancient manuscripts, original quotes, techniques, and illustrations. RESULTS: The story of rhinoplasty is one of peaks of achievement by individuals such as Sushruta, Branca, Tagliocozzi, Roe, and Joseph. Since Roe introduced the concept of cosmetic rhinoplasty, the evolution of nasal reconstructive techniques has reached such a level that the expectation is not only to restore form and function, but also to achieve excellent cosmetic appearance. CONCLUSIONS: Although repair of nasal injuries is the oldest form of reconstructive surgery, being cited in Egyptian papyrus inscriptions such as the Edwin Smith Papyrus dating back to 2500 to 3000 BC, its complexity continues to challenge surgeons today. This article is dedicated to those individuals who have devoted their lives and work to the advancement of the field of plastic surgery for the benefit of mankind.

Quantifying collagen type in mature burn scars: a novel approach using histology and digital image analysis.

Using Herovici staining and digital image analysis, we have studied the collagen subtype and fiber orientation in mature burn scars. These techniques have shown mature burn scars to have increased type I/type III collagen ratios compared with normal skin. Additionally, the collagen orientation of burn scars has been shown to be thickened, tightly packed, and lacking the "basket weave" appearance of normal skin specimens. These techniques allow the differentiation of type I collagen from type III collagen, the assessment of collagen orientation, and the analysis of scar architecture in terms of epidermis and papillary/reticular dermis contribution. These findings are important clinically because collagen subtype and fiber orientation may predict future scar activity. Any attempt to modify the scarring process can be directly measured and compared using this easily reproducible technique.