The pathological and biochemical identification of possible seed-lesions of transmitted transthyretin amyloidosis after domino liver transplantation.

The most serious issue in domino liver transplantation (DLT) using liver grafts from patients with transthyretin (TTR)-related familial amyloid polyneuropathy (FAP) is the development of iatrogenic transmitted amyloidosis (de novo amyloidosis) in DLT-recipients. However, little is known regarding the mechanisms of the initial stage of amyloid formation in these recipients. We detected initial lesions (possible seed-lesions) of this iatrogenic amyloidosis in two recipients following liver grafting from FAP patients.

A phase 1 multiple-dose study of orteronel in Japanese patients with castration-resistant prostate cancer.

Purpose: Orteronel (TAK-700) is a non-steroidal, selective, reversible inhibitor of 17,20-lyase. We evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effect of orteronel with or without prednisolone in Japanese patients with castration-resistant prostate cancer (CRPC).

Methods: We conducted a phase 1 study in men with progressive and chemotherapy-naïve CRPC.

Structural and biological constraints on diversity of regions immediately upstream of cleavage sites in calicivirus precursor proteins.

To address the regulation and evolution of precursor protein cleavability in caliciviruses, we examined constraints on diversity of upstream regions of calicivirus precursor cleavage sites. We performed alanine scanning and supplementary mutagenesis of amino acids at P1, P2, P3, and P4 sites using four viruses representing the four major genera of the family Caliciviridae. This study complements previous mutagenesis studies and shows strong restrictions in mutations at the P1 and P4 sites for effective cleavage reactions.

Distinct genotype and antigenicity among genogroup II sapoviruses.

SaV, a pathogen of acute gastroenteritis, is divided into five genogroups, GI to GV. However, the relation between SaV antigenicity and genetic clusters is not fully understood. We have recently identified two GII SaV strains, Mc10 and C12, which are grouped into the same cluster based on the polymerase but are grouped into distinct clusters based on the capsid.

Self-assembly of sapovirus recombinant virus-like particles from polyprotein in mammalian cells.

The SaV genome is a positive-sense, non-segmented single-strand RNA molecule of approximately 7.5 kb that is polyadenylated at its 3' terminus. The major capsid (VP1) of SaV is thought to be produced as the ORF1 polyprotein followed by cleavage, or translation from subgenomic RNA (3'-coterminal with the virus genome), or both.

Highly conserved configuration of catalytic amino acid residues among calicivirus-encoded proteases.

A common feature of caliciviruses is the proteolytic processing of the viral polyprotein catalyzed by the viral 3C-like protease encoded in open reading frame 1 (ORF1). Here we report the identification and structural characterization of the protease domains and amino acid residues in sapovirus (SaV) and feline calicivirus (FCV). The in vitro expression and processing of a panel of truncated ORF1 polyproteins and corresponding mutant forms showed that the functional protease domain is 146 amino acids (aa) in SaV and 154 aa in FCV.