To study the epidemiology of human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Japan, we conducted two nationwide surveys between October 1986 and March 1989. A total of 710 patients with HAM (definite HAM, 589; probable HAM, 121) were reported. Of the 589 patients with definite HAM, 69% were residents of the areas with the highest prevalence HTLV-I in Japan. To determine the importance of blood transfusion in the pathogenesis of HAM/TSP, we performed a case-control study in the Kagoshima district in southern Japan. Significantly more patients with HAM reported a history of blood transfusion (26/129, or 20%) than did subjects in a health survey of the general population (41/1,290, or 3%; odds ratio = 7.7, p less than 0.001) or than did hospitalized neurological patients (6/119, or 5%; odds ratio = 4.8, p less than 0.001). Furthermore, the cumulative percentages of the intervals between blood transfusion and the onset of the symptoms of HAM fit a lognormal curve, suggesting that transfusion was an important common exposure. Blood transfusion probably transmitted HTLV-I to the patients with transfusion-associated HAM because there was a significant decrease in the number of patients with the transfusion-associated HAM who received blood after implementation of nationwide screening of blood donors in 1986 (p = 0.004). In the first 2 years, screening the blood supply in Japan appears to have decreased the number of reported patients with HAM by 16%.
Formins are force-sensing proteins that regulate actin polymerization dynamics. Here, we applied stretching tension to individual actin filaments under the regulation of formin mDia1 to investigate the mechanical responses in actin polymerization dynamics. We found that the elongation of an actin filament was accelerated to a greater degree by stretching tension for ADP-G-actin than that for ATP-G-actin. An apparent decrease in the critical concentration of G-actin was observed, especially in ADP-G-actin. These results on two types of G-actin were reproduced by a simple kinetic model, assuming the rapid equilibrium between pre- and posttranslocated states of the formin homology domain two dimer. In addition, profilin concentration dramatically altered the force-dependent acceleration of actin filament elongation, which ranged from twofold to an all-or-none response. Even under conditions in which actin depolymerization occurred, applications of a several-piconewton stretching tension triggered rapid actin filament elongation. This extremely high force-sensing mechanism of mDia1 and profilin could be explained by the force-dependent coordination of the biphasic effect of profilin; i.e., an acceleration effect masked by a depolymerization effect became dominant under stretching tension, negating the latter to rapidly enhance the elongation rate. Our findings demonstrate that the biphasic effect of profilin is controlled by mechanical force, thus expanding the function of mDia1 as a mechanosensitive regulator of actin polymerization.
Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multi-organ failure, and high mortality. In Japan, appropriate notification measures based on the Infectious Disease Control law are mandatory for cases of STSS caused by β-haemolytic streptococcus. STSS is mainly caused by group A streptococcus (GAS). Although an average of 60-70 cases of GAS-induced STSS are reported annually, 143 cases were recorded in 2011. To determine the reason behind this marked increase, we characterized the emm genotype of 249 GAS isolates from STSS patients in Japan from 2010 to 2012 and performed antimicrobial susceptibility testing. The predominant genotype was found to be emm1, followed by emm89, emm12, emm28, emm3, and emm90. These six genotypes constituted more than 90% of the STSS isolates. The number of emm1, emm89, emm12, and emm28 isolates increased concomitantly with the increase in the total number of STSS cases. In particular, the number of mefA-positive emm1 isolates has escalated since 2011. Thus, the increase in the incidence of STSS can be attributed to an increase in the number of cases associated with specific genotypes.
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