Activation of bystander CD8+ T cells in a pediatric patient with acute hepatitis E.

Most children with acute hepatitis A virus (HAV) or hepatitis E virus (HEV) infection are asymptomatic. Bystander CD8+ T-cell activation has garnered attention owing to its possible pathophysiological role in adult hepatitis. However, no reports have studied it in pediatric hepatitis. Herein, we describe the case of a three-year-old girl with acute hepatitis by HEV genotype 1. She had a history of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections, and HEV hepatitis occurred shortly after asymptomatic HAV infection. Peripheral immunophenotyping revealed activation of non-HEV-specific CD8+ T cells which include EBV-specific and CMV-specific CD8+ T cells, during the acute phase. While alanine-aminotransferase levels declined after admission, the total number of activated CD8+ T cells increased for four days after admission and decreased thereafter. In contrast, activation of EBV-specific and CMV-specific CD8+ T cells was almost at the maximal level at the time of admission, which suggest development of activated bystander CD8+ T cells in the early stage. This case highlights the significance of the bystander CD8+ T-cell activation even in pediatric hepatitis and the size of the CD8+ T cell memory pool in the individuals for the development of hepatitis, given the patient's history of infections with EBV, CMV and HAV.

Re-irradiation using proton therapy for radiation-induced secondary cancer with Li-Fraumeni syndrome: A case report and review of literature.

Li-Fraumeni syndrome (LFS) is a genetic disease that is hypersensitive to radiotherapy. Proton therapy (PT) was strongly recommended for pediatric and radiation-sensitive tumors. However, there is little information on PT for LFS. The patient was a 7-year-old girl with LFS who was diagnosed with radiation-induced right shoulder blade osteosarcoma and left chest wall malignant fibrous histiocytoma. Both tumors were in the area that had previously been irradiated (36-45 Gy by photon radiotherapy). Sixty-six GyE in 30 fractions was planned for both tumors. We set the clinical target to the minimum gross tumor volume. To comprehensively assess any adverse events, PT was conducted under hospital administration. Cisplatin was used as simultaneous combination chemotherapy. Although administration of granulocyte-colony stimulating factor was necessary for myelosuppression by chemotherapy, PT was completed without interruption. Acute radiation toxicity was observed as Grade 1 dermatitis. The dermatitis became exacerbated 2 weeks after PT but subsequently improved with conservation treatment alone. Twenty-three months after PT, magnetic resonance imaging showed an increase in the tumor on the right shoulder. A histological examination was not conducted as the family declined, but secondary cancer was suggested rather than recurrent osteosarcoma, as the tumor developed mainly from the soft tissue. Additional surgical treatment and radiotherapy were not indicated, and the patient died of tumor progression and sepsis caused by myelosuppression 27 months after undergoing PT. Up to 23 months after PT, there were no signs of Grade 2 or more late toxicities. This represents the first reported case of PT for a patient with LF to treat radiation-induced secondary cancer.

Cationic Iridium/Chiral Bisphosphine-Catalyzed Enantioselective Hydroacylation of Ketones.

A facile and convenient synthesis of the chiral phthalide framework catalyzed by cationic iridium was developed. The method utilized cationic iridium/bisphosphine-catalyzed asymmetric intramolecular carbonyl hydroacylation of 2-keto benzaldehydes to furnish the corresponding optically active phthalide products in good to excellent enantioselectivities (up to 98% ee). The mechanistic studies using a deuterium-labelled substrate suggested that the reaction involved an intramolecular carbonyl insertion mechanism to iridium hydride intermediate. In addition, we investigated the kinetic isotope effect (KIE) of intramolecular hydroacylation with deuterated substrate and determined that the C-H activation step is not included in the turnover-limiting step.

Sequential Intermolecular Radical Addition and Reductive Radical Cyclization of Tyrosine and Phenylalanine Derivatives with Alkenes via Photoinduced Decarboxylation: Access to Ring-Constrained γ-Amino Acids.

Sequential radical addition to alkenes and reductive radical cyclization of phenylalanine and tyrosine derivatives via photoinduced decarboxylation furnished ring-constrained γ-amino acids under mild conditions. A variety of alkenes such as acrylamides and acrylic esters could be employed in the photoinduced radical cascade cyclization. The yields of the ring-constrained γ-amino acids are dependent on the electron-accepting ability and steric hindrance of the alkene used. The proposed sequential reaction can also be applied for direct tethering of dipeptides to yield unique ring-constrained tetrapeptides.

Synthesis of 23-, 25-, 27-, and 29-Membered ( Z)-Selective Unsaturated and Saturated Macrocyclic Lactones from 16- and 17-Membered Macrocyclic Lactones and Bromoalcohols by Wittig Reaction, Yamaguchi Macrolactonization, and Photoinduced Decarboxylative Radical Macrolactonization.

A new strategy for the synthesis of 23-, 25-, 27-, and 29-membered ( Z)-selective unsaturated and saturated macrocyclic lactones from commercially available 16- and 17-membered macrocyclic lactones and bromoalcohols by Wittig reaction, Yamaguchi macrolactonization, and photoinduced decarboxylative radical macrolactonization is described. The position of the unsaturated part in the macrocyclic lactones can be controlled by changing the number of carbons in the starting materials. This protocol can provide facile access to the desired large-ring ( Z)-selective unsaturated and saturated macrocyclic lactones from simple starting materials.

Strategy for O-Alkylation of Serine and Threonine from Serinyl and Threoninyl Acetic Acids by Photoinduced Decarboxylative Radical Reactions: Connection between Serine/Threonine and Carbohydrates/Amino Acids at the Side Chain.

O-Alkylations of serine and threonine derivatives at the hydroxy group were achieved using photoinduced decarboxylative radical reactions of serinyl and threoninyl acetic acids with an organic photocatalyst without racemization under mild conditions. Photoinduced decarboxylative radical additions of serinyl and threoninyl acetic acids to electron-deficient alkenes provided linked serine and threonine with carbohydrates and amino acids at the side chain. In addition, O-methylations containing deuterium and O-benzylation of serine were performed under similar photochemical conditions.

[Detailed magnetic resonance imaging of abducens nerve by 3D-CISS].

Although abducens nerve palsy is a relatively common disease, the abducens nerve has been almost impossible to identify, because it is one of the finest cranial nerves and runs three-dimensionally in the prepontine cistern. Three-dimensional constructive interference in steady state (3D-CISS) is helpful in visualizing fine structural elements in the central nervous system because of its higher spatial resolution and fewer artifacts from cerebrospinal fluid. In this study, we successfully visualized the abducens nerve using 3D-CISS. The procedures were as follows: first, Dorello's canal and the ponto-medullary sulcus were identified as visible landmarks, and then the abducens nerve was followed to the root exit zone; second, the gray scale of the original image was inverted to clearly visualize the cisternal course of the nerve and the neighboring small vessels; and, finally, the entire cisternal course of the nerve was visualized in the same images in both oblique axial and oblique sagittal planes by a multi-planar reconstruction method. This reliable technique can be performed for the diagnosis of abducens nerve palsy.