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Abstract: This study was conducted to determine the frequency and characteristics of supplement use in pediatric patients with allergic disorders in Japan. A total of 229 patients with various allergic disorders aged between 0 and 15 years were enrolled. Supplements were defined as preparations that provided nutritional content in the form of a tablet, capsule, powder, liquid, or jelly. The parents of each subject were asked to complete a questionnaire on their child''s use of supplements over the previous year. Demographic information, parents'' perceived view of the child''s health status over the previous month, and family history of both allergic disorders, and supplement use were collected. Four hundred eight age- and sex-matched healthy children served as the controls. Twenty-nine (12.7%) patients had used supplements. This frequency was not significantly different from that in the control group (15.0%). The types of supplements most commonly used were vitamins, followed by minerals, probiotics, and chlorella. Univariate analysis revealed that older age and a positive family history of supplement use were associated with patients'' supplement use. The types of allergic disorders, health status from the point of view of the parents, and a family history of allergic disorders did not show any significant association. To our knowledge, this is the first cross-sectional study to demonstrate the frequency and the factors affecting supplement use in pediatric patients with allergic disorders. [Copyright &y& Elsevier]

Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin's lymphoma. Most cases of MCL have extranodal involvement at the time of the initial diagnosis; however, endobronchial involvement is rare. An 87-year-old man was referred to our hospital because of dyspnea on exertion. A chest CT revealed diffuse irregular wall thickening of the trachea and bilateral bronchi. A bronchoscopy revealed a diffuse irregular surface of the tracheal and bilateral bronchial mucosa and polyposis-like lesions. He was diagnosed as having MCL based on an endobronchial biopsy, and the diagnosis was confirmed using immunohistochemical staining. [ABSTRACT FROM AUTHOR]

The persistence of anti-viral immunity is essential for protection and exhibits profound heterogeneity across individuals. Here, we elucidate the factors that shape maintenance and function of anti-viral T cell immunity in the body by comprehensive profiling of virus-specific T cells across blood, lymphoid organs, and mucosal tissues of organ donors. We use flow cytometry, T cell receptor sequencing, single-cell transcriptomics, and cytokine analysis to profile virus-specific CD8+ T cells recognizing the ubiquitous pathogens influenza and cytomegalovirus. Our results reveal that virus specificity determines overall magnitude, tissue distribution, differentiation, and clonal repertoire of virus-specific T cells. Age and sex influence T cell differentiation and dissemination in tissues, while T cell tissue residence and functionality are highly correlated with the site. Together, our results demonstrate how the covariates of virus, tissue, age, and sex impact the anti-viral immune response, which is important for targeting, monitoring, and predicting immune responses to existing and emerging viruses. [Display omitted] • CD8+ T cells specific for influenza and CMV localize in multiple tissue sites • Persistence of memory CD8+ T cell subsets is shaped by virus tropism and specificity • Regulation of functional responses to viral antigens is primarily tissue mediated • Age and sex influence T cell subset differentiation and tissue residency Through comprehensive cellular and molecular analysis of virus-specific T cells in circulation and across multiple lymphoid and mucosal tissues, Poon et al. elucidate how maintenance and function of the human anti-viral immune response against ubiquitous viruses influenza and cytomegalovirus are shaped by virus, tissue, age, and sex. [ABSTRACT FROM AUTHOR]

Hepatic arterial and portal venous anomalies in living liver donors are not uncommon. Modified surgical techniques may be required in such circumstances, although the safety of the living donor must always be given top priority. We describe here a successful portal venous reconstruction in a living donor with an anomalous hepatic arterial and portal venous anatomy in which the right anterior and posterior hepatic arteries encircled the main portal vein. Although such an anomaly of hepatic vessels was not frequently encountered, we should be able to alter the surgical strategy to deal with it. This case illustrates the importance of preoperative hepatic artery and portal venous evaluation in all living donors to identify the feasibility of modifying vessel anastomoses in living donors, as well as recipients, before living donor liver transplantation. [Copyright &y& Elsevier]

Non-recirculating tissue-resident memory T cells (TRMs) are the predominant T cell subset in diverse tissue sites, where they mediate protective immune responses in situ. Here, we reveal a role for TRM in maintaining immune homeostasis in the human pancreas through interactions with resident macrophages and the PD-1/PD-L1 inhibitory pathway. Using tissues obtained from organ donors, we identify that pancreas T cells comprise CD8+PD-1hi TRMs, which are phenotypically, functionally, and transcriptionally distinct compared to TRMs in neighboring jejunum and lymph node sites. Pancreas TRMs cluster with resident macrophages throughout the exocrine areas; TRM effector functions are enhanced by macrophage-derived co-stimulation and attenuated by the PD-1/PD-L1 pathways. Conversely, in samples from chronic pancreatitis, TRMs exhibit reduced PD-1 expression and reduced interactions with macrophages. These findings suggest important roles for PD-1 and TRM-macrophage interactions in controlling tissue homeostasis and immune dysfunctions underlying inflammatory disease, with important implications for PD-1-based immunotherapies. • The human pancreas contains CD8+ TRMs exhibiting tissue-specific molecular signatures • Pancreas TRMs express high levels of PD-1 yet maintain strong effector function • During homeostasis, pancreas TRMs are regulated by PD-L1+ tissue macrophages • In chronic pancreatitis, TRM PD-1 levels and PD-L1+ macrophage density are reduced Non-recirculating tissue-resident memory T cells (TRMs) mediate immune responses in non-lymphoid tissues. Using a human organ donor tissue resource, Weisberg et al. reveal that PD-1hi pancreas TRMs are regulated by PD-L1+ macrophages during homeostasis. Comparison with chronic pancreatitis patient samples shows how pancreas TRM regulation is altered during inflammation. [ABSTRACT FROM AUTHOR]

Abstract: A 2-year-old girl with Down syndrome (DS) developed acute megakaryoblastic leukemia (AMKL) following a transient myeloproliferative disorder (TMD). The blast cells showed an altered karyotype of 47,XX,r(7),+21c. Serial cytogenetic studies during the course of the illness showed rapid stepwise clonal chromosome changes, including a ring chromosome 7, associated with treatment refractoriness. We reviewed 10 published cases of Down syndrome-related AMKL (DS-AMKL) showing chromosome 7 abnormalities and found that these changes do not carry the same prognostic weight as for non-DS children. For DS-AMKL, therefore, other prognostic factors besides clonal cytogenetic changes need to be identified for planning optimal therapy. [Copyright &y& Elsevier]

Abstract: We have previously reported that calcium ionophore A23187 differentially induces necrosis in CEM cells, a T-lymphoblastic leukemia cell line, and apoptosis in HL60 cells, a promyelocytic leukemia cell line. Stimulation with VP16, however, induces typical apoptosis in both cell lines. Necrosis in CEM cells, characterized by cell shrinkage and clustering, began within 5 min of treatment. Swelling of the mitochondria, lumpy chromatin condensation and intact plasma membranes were evident by electron microscopy. These A23187-mediated changes in CEM cells were suppressed by clonazepam or CGP37157, inhibitors of the mitochondrial Na+/Ca2+ exchanger. The changes, however, were not affected by cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. In both CEM and HL60 cells, intra-cellular calcium increased with similar amplitude within 1 min of treatment with 2 μM A23187. Intra-mitochondrial calcium increased with clonazepam pre-treatment alone in both CEM and HL60 cells. However, intra-mitochondrial calcium did not change drastically in response to A23187 in CEM or HL60 cells, either untreated or pre-treated with clonazepam. A23187 induces necrosis in CEM cells concurrent with mitochondrial dysfunction, which is independent of the mitochondrial permeability transition, but affected by intra-mitochondrial calcium, while HL60 cells lack these early changes. Differences in the responses to A23187 between these two cell lines might derive from differences in the susceptibility of the mitochondrial membrane to rapid increases in intra-cellular calcium. [Copyright &y& Elsevier]

It has been shown that exogenous ceramide induces delayed neuronal death (DND) of cultured hippocampal neurons. To evaluate the role of endogenous ceramide in ischemic DND, the glucosylceramide synthase inhibitor, d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (d-PDMP), was used to generate ceramide in gerbil hippocampi in vivo. The trimethylsilylated derivatives of ceramide were analyzed directly by gas chromatography mass spectrometry, after separation with high-performance thin-layer chromatography. The ceramide compositions in vehicle hippocampus consisted mainly of C18:0 fatty acyl sphingosine (87.9%), with C16:0 and C20:0 ceramides being minor components (7.1% and 5.1%, respectively). Ceramide level in the hippocampi from gerbils subjected to d-PDMP treatment was 1.5-fold higher than those from vehicle-treated gerbils. In spite of the accumulation of ceramide observed in the d-PDMP group, the histological studies did not reveal any ischemic neuronal death in hippocampal CA1 neurons with the gerbils that had been subjected to a sham operation (2-min sublethal ischemia). These results suggest that the ceramide accumulation induced by blocking the de novo synthesis of glucosylceramide with d-PDMP may be independent of the metabolic pathway underlying ischemic DND. [Copyright &y& Elsevier]