The emergence and rapid spread of novel DS-1-like intergenogroup reassortant rotaviruses having the equine-like G3 genotype (DS-1-like G3P[8] strains) have been recently reported from several countries. During rotavirus surveillance in Japan in 2015-2016, three DS-1-like G3P[8] strains were identified from children with severe diarrhea. In the present study, we sequenced and characterized the full genomes of these three strains. On full-genomic analysis, all three strains showed a unique genotype constellation including both genogroup 1 and 2 genes: G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis revealed that each of the 11 genes of the three strains was closely related to that of Japanese DS-1-like G1P[8] and/or Japanese equine-like G3P[4] human strains. Thus, the three study strains were suggested to be reassortants that acquired the G3-VP7 gene from equine G3 rotaviruses on the genetic background of DS-1-like G1P[8] strains. Our observations will provide important insights into the evolutionary dynamics of emerging DS-1-like G3P[8] strains.

The immunologic effects of developmental exposure to noninherited maternal Ags (NIMAs) are quite variable. Both tolerizing influence and inducing alloreaction have been observed on clinical transplantation. The role of minor histocompatibility Ags (MiHAs) in NIMA effects is unknown. MiHA is either matched or mismatched in NIMA-mismatched transplantation because a donor of the transplantation is usually limited to a family member. To exclude the participation of MiHA in a NIMA effect for MHC (H-2) is clinically relevant because mismatched MiHA may induce severe alloreaction. The aim of this study is to understand the mechanism of NIMA effects in MHC-mismatched, MiHA-matched hematopoietic stem cell transplantation. Although all offsprings are exposed to the maternal Ags, the NIMA effect for the H-2 Ag was not evident. However, they exhibit two distinct reactivities, low and high responder, to NIMA in utero and during nursing depending on the degree of maternal microchimerism. Low responders survived longer with less graft-versus-host disease. These reactivities were correlated with Foxp3 expression of peripheral blood CD4+CD25+ cells after graft-versus-host disease induction and the number of IFN-γ–producing cells stimulated with NIMA pretransplantation. These observations are clinically relevant and suggest that it is possible to predict the immunological tolerance to NIMA.

The pharmacokinetics of tamsulosin hydrochloride in patients with renal impairment were compared with those in healthy volunteers, and the factors that influenced plasma levels of tamsulosin were elucidated. A single oral dose of 0.2 mg of tamsulosin was given and blood and urine samples were obtained for 36 hours after administration. Unbound plasma concentration of tamsulosin was measured by a combination of equilibrium dialysis and liquid chromatography tandem mass spectrometry methods to examine the effect of protein binding on the pharmacokinetics of tamsulosin. Mean values for maximum concentration (Cmax) and area under the concentration-time curve (AUC) of total drug (Cmax,t and AUC1) in patients with renal impairment were 73% and 211% greater, respectively, than those in healthy volunteers. Mean Cmax and AUC of unbound drug (Cmax,u and AUCu), however, were almost the same in the two groups. A high correlation was found between alpha 1-acid glycoprotein (alpha 1-AGP) concentration and AUCt, but no correlation was found between alpha 1-AGP concentration and AUCu,0-36) or between creatinine clearance (ClCR) and AUCu,0-36). These results show that in patients with renal impairment, the pharmacokinetics of tamsulosin are affected by the change in protein binding that is associated with alteration of plasma alpha 1-AGP concentration, but are not largely affected by the decrease in the renal excretion. Although total tamsulosin levels increased as plasma protein binding increased, unbound tamsulosin levels (which are directly associated with the pharmacologic effects) remained unchanged in these patients.

Rotavirus A (RVA), a member of the genus Rotavirus and family Reoviridae, comprises an 11-segment RNA genome encoding 6 structural proteins (VP1-VP4, VP6, and VP7) and 6 non-structural proteins (NSP1-NSP6). Majority of the human RVAs have genes with sequences similar to those of the prototype human strain Wa (genogroup 1) or DS-1 (genogroup 2) gene. Walike strains are characterized by the non-G/P genotype I1-R1-C1-M1-A1-N1-T1-E1-H1 and tend to possess G/P genotypes G1P[8], G3P[8], G4P[8], G9P[8], and G12P[8]. In contrast, DS-1-like strains are characterized by the non-G/P genotype I2-R2-C2-M2-A2-N2-T2-E2-H2 and tend to have the G/P genotype G2P[4] (1). The rapid emergence and spread of novel intergenogroup reassortant strains have recently been reported in several countries (2). Of these, DS-1-like G8P[8] strains with bovine-like G8 genotypes have recently emerged as major strains in Thailand, Vietnam, and Japan in Asia (3-7).

The emergence of unusual G9P[8]-E2 human rotaviruses in the Tokyo metropolis, Japan in 2018 has been reported. During rotavirus strain surveillance in different regions of Japan (Mie, Okayama, and Chiba prefectures), G9P[8]-E2 strains were detected in diarrheic children in all three prefectures. Here, we characterized the whole genomes of seven representative G9P[8]-E2 strains. On full-genome-based analysis, the seven study strains exhibited a unique genotype configuration having the NSP4 gene of genogroup 2 in a genogroup 1 genomic backbone: G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1. This genotype constellation is shared by Tokyo G9P[8]-E2 strains. Phylogenetic analysis showed that all the 11 genes, except the NSP4 one, of the seven study strains appeared to have originated from co-circulating Wa-like G9P[8]-E1 strains. On the other hand, the NSP4 gene appeared to have originated from co-circulating DS-1-like G2P[4]-E2 strains. Thus, these study G9P[8]-E2 strains appeared to be derived through reassortment between G9P[8]-E1 and G2P[4]-E2 strains in Japan. Notably, the seven study G9P[8]-E2 strains and Tokyo G9P[8]-E2 strains were revealed to have 11-segment genomes almost indistinguishable from one another in their sequences (99.3-100%), indicating all these G9P[8]-E2 strains had a common origin. To our knowledge, this is the first description of the rapid spread of G9P[8]-E2 strains across a country.