Efficient Activation of Human T Cells of Both CD4 and CD8 Subsets by Urease-Deficient Recombinant Mycobacterium bovis BCG That Produced a Heat Shock Protein 70-M. tuberculosis-Derived Major Membrane Protein II Fusion Protein

For the purpose of obtaining Mycobacterium bovis bacillus Calmette-Guérin (BCG) capable of activating human naive T cells, urease-deficient BCG expressing a fusion protein composed of Mycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (BCG-DHTM) was produced. BCG-DHTM secreted the HSP70-MMP-II fusion protein and effectively activated human monocyte-derived dendritic cells (DCs) by inducing phenotypic changes and enhanced cytokine production. BCG-DHTM-infected DCs activated naive T cells of both CD4 and naive CD8 subsets, in an antigen (Ag)-dependent manner. The T cell activation induced by BCG-DHTM was inhibited by the pretreatment of DCs with chloroquine. The naive CD8⁺ T cell activation was mediated by the transporter associated with antigen presentation (TAP) and the proteosome-dependent cytosolic cross-priming pathway. Memory CD8⁺ T cells and perforin-producing effector CD8⁺ T cells were efficiently produced from the naive T cell population by BCG-DHTM stimulation. Single primary infection with BCG-DHTM in C57BL/6 mice efficiently produced T cells responsive to in vitro secondary stimulation with HSP70, MMP-II, and M. tuberculosis-derived cytosolic protein and inhibited the multiplication of subsequently aerosol-challenged M. tuberculosis more efficiently than did vector control BCG. These results indicate that the introduction of MMP-II and HSP70 into urease-deficient BCG may be useful for improving BCG for control of tuberculosis.     

Bacterial meningitis after radiofrequency diathermy for adenoid hypertrophy

A 6‐year‐old otherwise healthy girl who underwent radiofrequency diathermy for adenoid hypertrophy presented with fever on the same day and was diagnosed as having bacterial meningitis 2 days later. Culture of cerebrospinal fluid indicated that the pathogens were penicillin‐sensitive Streptococcus pneumoniae and methicillin‐sensitive Staphylococcus aureus. The serotype of the causative pneumococcus, 11A, was not covered by the 7‐valent pneumococcal conjugate vaccine the patient had been inoculated with. Although not previously reported, radiofrequency diathermy for adenoid hypertrophy can be considered a risk factor for bacteremia and meningitis.     

Infrequent alterations of the p16INK4A gene in liver cancer

We examined the genomic status of the p16^INK4A (inhibitor of cyclin-dependent kinase 4 A) and cyclin-dependent kinase 4 (CDK4) genes in 62 human hepatocellular carcinomas (HCCs), 5 cholangiocellular carcinomas and 6 cell lines derived from human liver cancers. Although no samples showed the homozygous deletion of the p16^INK4A gene, we detected intragenic mutations of the p16^INK4A gene in 3 HCCs and one HCC cell line, which led to an amino-acid substitution or a frameshift. In 2 HCC samples with mis-sense mutations of the p16^INK4A gene, loss of heterozygosity on 9p22 was also detected, suggesting that the loss of function of p16 was induced during hepatocarcinogenesis. On the other hand, amplification or rearrangement of the CDK4 gene was not detected in any samples examined in this study. These results indicated that the mutations or deletions of the p16^INK4A gene are not frequent, but may play a role in a sub-set of human HCC. © 1996 Wiley-Liss, Inc.     

Acquired Thrombotic Thrombocytopenic Purpura Following BNT162b2 mRNA Coronavirus Disease Vaccination in a Japanese Patient

A 57-year-old man without underlying diseases presented with fatigue, loss of appetite, and jaundice 1 week after receiving the first dose of the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine and showed hemolytic anemia with fragmented erythrocytes and severe thrombocytopenia 2 weeks after receiving the vaccine. An a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity level of <10% and ADAMTS13 inhibitor positivity confirmed the diagnosis of acquired thrombotic thrombocytopenic purpura (TTP). Combination therapy with plasma exchange, corticosteroid, and rituximab improved the clinical outcome. We herein report the first Japanese case of TTP possibly associated with vaccination. Physicians should be alert for this rare but life-threatening hematological complication following COVID-19 vaccination.     

Preparation of a platinum nanoparticle catalyst located near photocatalyst titanium oxide and its catalytic activity to convert benzyl alcohols to the corresponding ethers

A novel platinum nanoparticle catalyst closely located near the surface of titanium oxide, PtNP/TiO₂, has been prepared. This catalyst has both the properties of a photocatalyst and a metal nanoparticle catalyst, and acquired environmentally friendly catalytic activity, which cannot be achieved by just one of these catalysts, to afford ethers from benzyl alcohols under the wavelength of 420 nm.

A novel platinum nanoparticle catalyst closely located near the surface of titanium oxide, PtNP/TiO₂, has been prepared. It has catalytic activity to afford ethers from benzyl alcohols under the wavelength of 420 nm.

The electrolysis of water by a heterogeneous metal oxide semiconductor (MOS) photocatalyst, called the Honda–Fujishima effect,¹ received considerable attention because it enables the conversion of solar energy. As a result, photoreactions by heterogeneous photocatalysts based on MOS have been reported until now, including numerous practical applications such as carbon dioxide reduction² and pollutant removal.³Research on photocatalytic reactions using visible light is progressing steadily. Among them, TiO₂ has been extensively studied due to its high catalytic activity, low cost, non-toxicity, and long-term stability.^4,5Titanium oxide has a very strong oxidizing power, but it does not have a strong reducing power.⁶ By using a transition metal such as platinum on titanium oxide as a support, its reducing power can be increased, and the amount of hydrogen generated in the electrolysis of water can be improved eight times compared to the case of titanium oxide alone.⁷Furthermore, when MOS contacts the metal, a potential barrier called Schottky barrier is formed at the interface. The basic characteristic of this Schottky barrier lies in the Schottky barrier height (Φ), which represents the difference between the CB of the MOS distorted by the contact with a metal and the Fermi level (E_F) of the metal. Although it has been studied for almost half a century, how to determine the barrier is still not well understood. Due to the formation of the Schottky barrier height, the energy required to move the electrons from the valence band of MOS to the conductor changes from E_g to Φ, and the energy becomes smaller and it changes to a longer wavelength. As a result, a photoreaction with titanium oxide using light with a wavelength longer than 387 nm has also been reported (Scheme 1)⁸Open in a separate windowScheme 1Effect of sunlight exposure on aerobic oxidation of alcohols with the Pt/TiO₂ catalysts.On the other hand, we have recently developed a sulfur-modified Au-supported Pd NP catalyst (SAPd) that is applicable in Suzuki–Miyaura coupling^9a,9b and C–H functionalization^9c (Scheme 2a). It was constructed by approximately 10 layers of self-assembled Pd(0) NPs (mean size: <5 nm) supported on a sulfur-modified Au surface. We speculated that the self-assembled Pd NPs, which were encapsulated in a sulfated p-xylene polymer matrix,^9d were formed using in situ metal NP and nanospace simultaneous organization (PSSO), as illustrated in Scheme 2b: (i) the reduction of a high-valence metal source, (ii) growth of transition metal NPs, (iii) growth of a matrix with appropriately sized nanopores, and (iv) encapsulation of the metal NPs in these nanopores. To prepare SARu,¹⁰ SANi,¹¹ SAFe(ii),¹² and SAFe(0)¹³ (Scheme 2a), the PSSO method involves the in situ reduction of a noble metal precursor to produce in situ metal NPs.Open in a separate windowScheme 2(a) Preparation of SAPd, SARu, SANi, SAFe(II) and SAFe(0) by combining in situ PSSO with an organic reductant, (b) in situ metal nanoparticle and nanospace simultaneous organization (PSSO) method and the image of the SAPd structure and (c) the preparation of PtNP/TiO₂.In this research project, we decided to create a novel metal NP catalyst having metal NPs near the surface of TiO₂ by substituting the gold-supported SAPd for gold with a titanium oxide (TiO₂) photocatalyst. Alternatively, by substituting the solid gold support for a photocatalyst, we thought that we could create a novel metal NPs catalyst with an unprecedented reactivity by combining the properties of both photocatalyst and metal nanoparticle catalyst (Scheme 2c).     

Parallel enlargement of Marinesco bodies and nuclei and progressive deposition of p62 in pigmented neurons of the substantia nigra

Marinesco bodies (MBs) are spherical nuclear inclusions found in pigmented neurons of the substantia nigra. Although MBs are abundant in senescent brains, how they are related to aging processes remains unclear. Here, we performed a morphometric analysis of midbrain pigmented neurons to identify the possible influence of MBs on nuclear size. The transected area of the nucleus (nuclear area) was larger in the presence of MBs and was correlated with the area of MB (MB area) in all tested brains. The MB-associated nuclear enlargement was significant even after MB areas were subtracted from nuclear areas. Moreover, higher MB immunoreactivity of p62 was detected in the nucleoplasm of the enlarged MB-associated nuclei. This study on human brains is the first quantitative approach demonstrating MB-associated nuclear enlargement and progressive accumulation of small nucleoplasmic materials. Although cellular hypertrophy is usually considered to be an indication of the upregulation of cellular function, this might not always be the case. These findings suggest that an age-related decline of ubiquitin-proteasome and autophagy system activity and stagnation of undegradable materials are one of the candidate mechanisms to explain the age-related decline of neural activity in the substantia nigra.