This is the first case of Plasmodium knowlesi infection in a Japanese traveller returning from Malaysia. In September 2012, a previously healthy 35-year-old Japanese man presented to National Center for Global Health and Medicine in Tokyo with a two-day history of daily fever, mild headaches and mild arthralgia. Malaria parasites were found in the Giemsa-stained thin blood smear, which showed band forms similar to Plasmodium malariae. Although a nested PCR showed the amplification of the primer of Plasmodium vivax and Plasmodium knowlesi, he was finally diagnosed with P. knowlesi mono-infection by DNA sequencing. He was treated with mefloquine, and recovered without any complications. DNA sequencing of the PCR products is indispensable to confirm P. knowlesi infection, however there is limited access to DNA sequencing procedures in endemic areas. The extent of P. knowlesi transmission in Asia has not been clearly defined. There is limited availability of diagnostic tests and routine surveillance system for reporting an accurate diagnosis in the Asian endemic regions. Thus, reporting accurately diagnosed cases of P. knowlesi infection in travellers would be important for assessing the true nature of this emerging human infection.
The gene encoding the methionine salvage pathway methylthioadenosine phosphorylase (MTAP) is a tumor suppressor gene that is frequently inactivated in a wide variety of human cancers. In this study, we have examined if heterozygosity for a null mutation in Mtap (Mtap(lacZ)) could accelerate tumorigenesis development in two different mouse cancer models, E?-myc transgenic and Pten(+/-) .
The semi-invariant natural killer (NK) T-cell receptor (NKTcr) recognises structurally diverse glycolipid antigens presented by the monomorphic CD1d molecule. While the alpha-chain of the NKTcr is invariant, the beta-chain is more diverse, but how this diversity enables the NKTcr to recognise diverse antigens, such as an alpha-linked monosaccharide (alpha-galactosylceramide and alpha-galactosyldiacylglycerol) and the beta-linked trisaccharide (isoglobotriaosylceramide), is unclear. We demonstrate here that NKTcrs, which varied in their beta-chain usage, recognised diverse glycolipid antigens with a similar binding mode on CD1d. Nevertheless, the NKTcrs recognised distinct epitopic sites within these antigens, including alpha-galactosylceramide, the structurally similar alpha-galactosyldiacylglycerol and the very distinct isoglobotriaosylceramide. We also show that the relative roles of the CDR loops within the NKTcr beta-chain varied as a function of the antigen. Thus, while NKTcrs characteristically use a conserved docking mode, the NKTcr beta-chain allows these cells to recognise unique aspects of structurally diverse CD1d-restricted ligands.
Naturally occurring antibodies (NAbs) produced by CD5(+) B-1 B cells include those with specificity for thymocytes (anti-thymocyte autoantibody, ATA). Here we describe a prototypic example, encoded by an unmutated immunoglobulin ?/? heavy chain/light chain. Studies with ATA-? ("heavy chain only") transgenic mice demonstrated a critical requirement for self-antigen in the accumulation of B cells with this specificity and for the production of high levels of serum ATA NAb. Furthermore, analysis of B-cell development in ATA-?? ("heavy and light chain") transgenic mice revealed two distinct responses by B cells to expression of this B-cell receptor (BCR). (1) Most B cells developing from bone marrow of adult mice were blocked at an immature stage in spleen and only escaped apoptosis by editing their BCR to eliminate the ATA specificity. (2) Some B cells differentiated to antibody-forming cells without altering their specificity, produced high levels of serum ATA, and many ATA-secreting plasma cells were observed in spleen. Finally, examination of B-cell development and ATA NAb production in ATA-?? transgenic mice with levels of Thy-1 autoantigen varying from very low to above physiologic reveals a clear relationship between BCR crosslinking by antigen and B-cell fate. Low levels of Thy-1 autoantigen resulted in diversion of ATA B cells into the marginal zone B-cell compartment, presumably because of reduced BCR signaling. Thus, our studies demonstrate a key positive selection step in the development of NAb-producing B cells and show that most of these cells in adult mice bearing such specificities fail to reach a mature stage. Importantly, because these specificities are isolated from B-1 B cells and, when expressed as transgenes, guide development into the B-1 or marginal zone B-cell pool, we identify these B cells as a major source of natural autoantibodies in mice.
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