We describe a 58-year-old man with a malignant melanoma metastasis to the liver. After initiation of nivolumab therapy, he developed destructive thyroiditis and subsequently simultaneous isolated adrenocorticotropic hormone (ACTH) deficiency and severe hypercalcemia. Although isolated ACTH deficiency and hypercalcemia due to nivolumab therapy are both rare occurrences, these conditions can often cause a severe clinical course accompanied by a disturbance of consciousness. Therefore, clinicians should pay attention to these possible side effects of nivolumab if the patients have clinical symptoms, such as fatigue and a disturbance of consciousness.

Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome, and NICTH associated with gastrointestinal stromal tumor (GIST) is even more rare. Herein, we describe a patient with severe NICTH due to GIST who had developed liver cirrhosis as a consequence of chronic hepatitis B. Although circulating insulin, Cpeptide, and insulin-like growth factor-1 (IGF-1) levels were significantly decreased, in contrast to our expectations, the growth hormone (GH) level was slightly elevated. Steroid therapy with prednisolone appeared to be effective for the prevention of severe and continuous hypoglycemia.

Antifreeze proteins (AFPs) facilitate cold-survival of the organisms living under freezing environment by inhibiting ice crystal growth. In this study, we focused on a fungal AFP denoted TisAFP secreted from a psychrophilic snow-mold fungus, Typhula ishikariensis. It reported seven isoforms of TisAFP that share a high sequence identity. Significantly, fluorescencebased ice plane affinity (FIPA) analysis showed that the ice binding specificity of TisAFP8 is quite different from the others. To clarify what determines the uniqueness of TisAFP8, we performed mutagenesis experiments on TisAFP8, especially on the residues constructing its putative ice-binding site. The data suggested an importance of inward pointing residues not just outward pointing residues of TisAFP8. 3P044 Thg1-like タンパク質の機能構造解析A guanylyl base (G -1 ) of histydyl tRNA (tRNA His ) is an important element for tRNA recognition of HisRS. In eukaryotes, G -1 is added by tRNA His guanylyltransferase (Thg1) which functions as a reverse polymerase. Interestingly, some archaea and bacteria possess Thg1-like-protein (TLP) although G -1 of tRNA His is genomically encoded. Previous studies show that archaeal TLPs add nucleotides to 5'-truncated tRNAs, suggesting that TLPs may work as a repair enzyme of tRNAs. Moreover, there are differences in tRNA recognition and cofactor affinity between TLPs and Thg1. Here, we determined the structures of archaeal TLP (aTLP), aTLP-ATP, and aTLP-GTP. The structural differences between TLPs and Thg1 provide important information for understanding the reaction mechanism of TLP. 3P045 Staphylococcal nuclease と Δ44-49 変異体の構造揺らぎの解 析：酵素活性への洞察( 1 Nara Women's Univ., 2 Nippon Med. Sch., 3 Tokyo Tech, 4 JAIST)Staphylococcal nuclease (SNase) is one of the proteins whose structural fluctuations play important roles in enzymatic activities. Omega-loop deletion mutant (Δ44-49) of SNase shows reduced enzymatic activity, while its structure and ligand-binding activity are similar to those of the wild type (Wt). However the relationship between the enzymatic activity and fluctuations still remains unclear. To investigate the structural fluctuations of SNase related to the enzymatic activity, MD simulations of Wt and Δ44-49 were conducted in three ligand-binding states: a ligandfree, Ca2+-bound, and prAp & Ca2+-bound states. We will show the results of the simulations and discuss the role of the structural fluctuation on the enzymatic activity. 3P046サルモネラ菌べん毛繊維の多型変換における Glu114 と Glu121 の役割