Macrothrombocytopenia with leukocyte inclusions is a rare autosomal dominant platelet disorder characterized by a triad of giant platelets, thrombocytopenia, and characteristic Döhle body-like leukocyte inclusions. A previous study mapped a locus for the disease on chromosome 22q12.3-q13.2 by genome-wide linkage analysis. In addition, the complete DNA sequence of human chromosome 22 allowed a positional candidate approach, and results here indicate that the gene encoding nonmuscle myosin heavy chain-A, NMMHC-A, is mutated in this disorder. Mutations were found in 6 of 7 Japanese families studied: 3 missense mutations, a nonsense mutation, and a one-base deletion resulting in a premature termination. Immunofluorescence studies revealed that NMMHC-A distribution in neutrophils appeared to mimic the inclusion bodies. These results provide evidence for the involvement of abnormal NMMHC-A in the formation of leukocyte inclusions and also in platelet morphogenesis.

The adhesin pertactin (Prn) is one of the major virulence factors of Bordetella pertussis, the etiological agent of whooping cough. However, a significant prevalence of Prn-deficient (Prn−) B. pertussis was observed in Japan. The Prn− isolate was first discovered in 1997, and 33 (27%) Prn− isolates were identified among 121 B. pertussis isolates collected from 1990 to 2009. Sequence analysis revealed that all the Prn− isolates harbor exclusively the vaccine-type prn1 allele and that loss of Prn expression is caused by 2 different mutations: an 84-bp deletion of the prn signal sequence (prn1ΔSS, n = 24) and an IS481 insertion in prn1 (prn1::IS481, n = 9). The frequency of Prn− isolates, notably those harboring prn1ΔSS, significantly increased since the early 2000s, and Prn− isolates were subsequently found nationwide. Multilocus variable-number tandem repeat analysis (MLVA) revealed that 24 (73%) of 33 Prn− isolates belong to MLVA-186, and 6 and 3 Prn− isolates belong to MLVA-194 and MLVA-226, respectively. The 3 MLVA types are phylogenetically closely related, suggesting that the 2 Prn− clinical strains (harboring prn1ΔSS and prn1::IS481) have clonally expanded in Japan. Growth competition assays in vitro also demonstrated that Prn− isolates have a higher growth potential than the Prn+ back-mutants from which they were derived. Our observations suggested that human host factors (genetic factors and immune status) that select for Prn− strains have arisen and that Prn expression is not essential for fitness under these conditions.

We produced transgenic mice expressing T cell receptor-alpha beta chain genes, derived from the chicken ovalbumin (OVA)-specific I-Ad-restricted CD4+CD8- T helper cell clone 7-3-7. In transgenic mice with H-2d genetic background (Tg-d mice), delayed-type hypersensitivity (DTH) was induced in the hind footpad by one inoculation with OVA without any previous sensitization, suggesting that naive T cells have the potential to be involved in DTH response. Spleen cells from nonimmunized Tg-d mice showed a strong T cell proliferative response to in vitro stimulation with OVA. Furthermore, these spleen cells produce cytokines including interleukin(IL)-2, IL-3, interferon-gamma, granulocyte/macrophage colony-stimulating factor, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, which may play an important role in the attraction of mononuclear cells to an antigen-challenging site.

Fas ligand (FasL), either in the membrane bound form or soluble form, has cytotoxic activity against Fas-expressing cells. We report a case of nasal lymphoma accompanied by liver damage and pancytopenia. The serum level of soluble FasL (sFasL) was very high on admission, but rapidly decreased to normal levels after chemotherapy for lymphoma. Liver damage and pancytopenia also improved with the decrease in serum sFasL. Since Fas is expressed on both hepatocytes and haemopoietic cells, these facts suggest that FasL was expressed on lymphoma cells and directly associated with pathogenesis of liver damage and pancytopenia through its cytotoxic activity.

Bordetella pertussis is the aetiologic agent of whooping cough, a common cause of severe respiratory illness in children and prolonged mild cough in adults. To understand some of the reasons for differences in clinical symptoms between adults and children, we measured B. pertussis DNA loads in nasopharyngeal swabs (NPS) from 19 adults and 40 children (including 14 infants) by quantitative IS481 real-time PCR. All cases had been pre-diagnosed with the B. pertussis-specific loop-mediated isothermal amplification method. The mean PCR threshold cycles for adult and child NPS were 34.9 and 27.1, respectively, indicating a significantly lower B. pertussis DNA load in adults than in children (p <0.001). Moreover, adults had very low DNA loads during both early and later stages of the disease. When corresponding bacterial loads in NPS were calculated for B. pertussis Tohama cells using a standard curve, the mean number of bacterial cells taken with a rayon-tipped swab from an adult, older child and infant was estimated to be 320 (95% CI 120-910), 2.1 × 10⁴(95% CI 5.3 × 10³ to 8.3 × 10⁴) and 1.1 × 10⁶ cells (95% CI 1.2 × 10⁵ to 8.9 × 10⁶), respectively. This indicates that the B. pertussis load in NPS is closely correlated with patient age. Our observations suggest that adult pertussis is characterized by a lower bacterial load in the nasopharynx, resulting in milder symptoms and negative cultures.