Solution-phase synthesis of oligodeoxyribonucleotides using the H-phosphonate method with N-unprotected 5'-phosphite monomers.

Recent advances in nucleic acid therapeutics increase the requirements for developing efficient methods for the chemical synthesis of oligodeoxyribonucleotides (ODNs). In this study, we report a new approach for the solution-phase synthesis of ODNs using the H-phosphonate method with N-unprotected 5'-phosphite monomers. The 5'-phosphite monomers are synthesized in a single step from unprotected 2'-deoxyribonucleosides using 5'-O-selective phosphitylation and can be applied to the synthetic cycle of the H-phosphonate method. We synthesized four kinds of 5'-phosphite monomers and then optimized the conditions for the condensation between the 3'-hydroxy groups of the 5'-phosphite monomers and the H-phosphonate monoesters. As a result of various investigations, solution-phase synthesis of trithymidine diphosphate (TTT) and tetramers containing four kinds of nucleobases was achieved according to the procedure consisting of repeated condensation, deprotection, and purification using simple extraction or precipitation.

Serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab.

Nivolumab, a blockade of programmed cell death 1, is now administrated for advanced malignant melanomas. Nivolumab-associated adverse events include organ-specific autoimmune disorders; autoimmune thyroid disease, vitiligo and insulin-dependent diabetes. However, predisposed persons are currently unknown. Here, we report serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab: one with Hashimoto disease and another with probable subclinical Hashimoto disease. We should verify if nivolumab-related hypothyroidism and hyperthyroidism are predisposed to occur in euthyroid individuals with subclinical autoimmune thyroid disease.

Refractory bullous pemphigoid leaving numerous milia during recovery.

Recovery with milia may occur in bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and epidermolysis bullosa acquisita (EBA). Scarring commonly occurs in MMP and EBA. Here, we report a 62-year-old man patient with BP, who was left with numerous milia during recovery. The patient had immunoglobulin (Ig)G autoantibodies to the recombinant protein of the BP180-NC16a domain and the soluble 120-kDa ectodomain of BP180 (linear IgA bullous dermatosis [LAD]-1). There are cases of BP with IgG autoantibodies to LAD-1 and/or the recombinant protein of BP180 C-terminal domain. Extensive milia formation during recovery may be associated with immunological predisposition and/or improper interaction between hemidesmosomes and the extracellular matrix components.

New approach to the evaluation of skin color of pigmentary lesions using Skin Tone Color Scale.

Objective methods of measuring skin color are needed to evaluate pigmentary lesions quantitatively. We have developed a new method of measuring skin color using a plastic bar system called the Skin Tone Color Scale based on Munsell's color space system. We have also evaluated the effectiveness of various therapies using this measurement system. Our system was designed to measure skin color in normal skin, pigmentary lesions of solar lentigo, chloasma and ephelides, and postinflammatory pigmentation. Moreover, effectiveness of various therapies for these pigmentary lesions was evaluated. The evaluations made with this system were closely related to physician assessment. This method may be useful in measuring of skin color and evaluating the effectiveness of therapies for pigmentary diseases.