Impact of frequency and duration of freeze-dried inactivated tissue culture hepatitis A vaccine (Aimmugen®) vaccination on antibody titers; a japanese cross-sectional study.

BACKGROUND: The effect of the timing of additional doses and the long-term persistence of lyophilized inactivated tissue culture hepatitis A (HA) vaccine (Aimmugen®) on antibodies is unknown. METHODS: A single-center, cross-sectional, observational study was conducted in collaboration with the Japan Air Self-Defense Force, whose personnel were immunized with Aimmugen® when deployed to endemic areas. Patients who consented to this study after a medical examination with blood sampling between June 2022 and February 2023 were included; HA-IgG level in the residual serum was measured using the chemiluminescent immunoassay method. The exact vaccination history was investigated based on immunization records maintained by the Ministry of Defense, and a questionnaire was used to collect confounding factors. RESULTS: Of the 181 participants observed, 49 were in the unvaccinated group, and 132 were in the vaccinated group. Out of the vaccinated group, 6.8 % received either one or two doses, 40.9 % received three doses, and 52.3 % received more than four doses. IgG antibody titers (S/CO value) in each group (0, 1 or 2, 3, and over 4) increased in a frequency-dependent manner, with those vaccinated over four times showing significantly higher IgG antibody titers than all other groups (0.19 ± 0.10 vs 3.66 ± 3.00 vs 7.63 ± 3.57 vs 10.57 ± 1.86, respectively). When the number of months elapsed from the last vaccination to the date of blood collection in each group was plotted against IgG antibody titer, the slope of the regression line flattened out from a decreasing trend in the order 1 or 2, 3, over 4. CONCLUSIONS: Three doses of Aimmugen® are efficacious, but four or more doses induce more robust and sustained antibody production. Additionally, four or more doses may be effective when there is a need to ensure long-term immunity or risk of prolonged exposure.

Estimation of Sobolev embedding constant on a domain dividable into bounded convex domains.

This paper is concerned with an explicit value of the embedding constant from [Formula: see text] to [Formula: see text] for a domain [Formula: see text] ([Formula: see text]), where [Formula: see text]. We previously proposed a formula for estimating the embedding constant on bounded and unbounded Lipschitz domains by estimating the norm of Stein's extension operator. Although this formula can be applied to a domain Ω that can be divided into a finite number of Lipschitz domains, there was room for improvement in terms of accuracy. In this paper, we report that the accuracy of the embedding constant is significantly improved by restricting Ω to a domain dividable into bounded convex domains.

K604, a specific acyl­CoA:cholesterol acyltransferase 1 inhibitor, suppresses proliferation of U251­MG glioblastoma cells.

Glioblastoma is the most aggressive type of brain tumor and has a poor prognosis. Increased levels of cholesteryl ester and simultaneous expression of acyl­CoA:cholesterol acyltransferase 1 (ACAT1) in tumor cells indicated that cholesterol esterification is critical to tumor growth. The present study confirmed that human glioblastoma tissues as well as the glioblastoma cell line U251­MG showed significant expression of ACAT1. ACAT1 expression in U251­MG cells increased in a cell proliferation­dependent manner. K604, a selective ACAT1 inhibitor, suppressed the proliferation of U251­MG cells and downregulated the activation of Akt and extracellular signal­regulated kinase in proliferating glioblastoma cells. These results suggested that ACAT1 may be a therapeutic target for the treatment of glioblastoma, with K604 as an effective therapeutic agent.

Cellular interaction and cytotoxicity of the iowa mutation of apolipoprotein A-I (ApoA-IIowa) amyloid mediated by sulfate moieties of heparan sulfate.

The single amino acid mutation G26R in human apolipoprotein A-I (apoA-I) is associated with familial amyloid polyneuropathy III. ApoA-I carrying this mutation (apoA-IIowa) forms amyloid fibrils in vitro. Heparan sulfate (HS) is a glycosaminoglycan that is abundant at the cell surface and in the extracellular matrix. Although HS and its highly sulfated domains are involved in aggregation of amyloid-ß and accumulate in cerebral amyloid plaques of patients with Alzheimer disease and mouse models of this disease, the role of HS in familial amyloid polyneuropathy III has never been addressed. Here, we used cell models to investigate the possible role of HS in the cytotoxicity of apoA-IIowa amyloid. Wild-type CHO cells, but not pgsD-677 cells, an HS-deficient CHO mutant, demonstrated uptake of apoA-IIowa amyloid after incubation with the amyloid. Addition of sulfated glycosaminoglycans to culture media prevented interaction with and cytotoxicity of apoA-IIowa amyloid to CHO cells. Elimination of cell surface HS or inhibition of HS sulfation with chemical reagents interfered with interaction of apoA-IIowa amyloid with CHO cells. We also found that cellular interaction and cytotoxicity of apoA-IIowa amyloid were significantly attenuated in CHO cells that stably expressed the human extracellular endoglucosamine 6-sulfatases HSulf-1 and HSulf-2. Our results thus suggest that cell surface HS mediates cytotoxicity of apoA-IIowa amyloid and that enzymatic remodeling of HS mitigates the cytotoxicity.