A case of thymic cyst with thymic hyperplasia]

A 70-year-old man was admitted to our hospital for treatment of an anterior mediastinal tumor. Although he was asymptomatic, an abnormal shadow was visible on chest radiography. CT revealed a heterogeneous tumor located in the anterior mediastinum. On MRI, the tumor demonstrated low signal intensity in T1-weighted images and high signal intensity in T2-weighted images. Laboratory data, including tumor markers, were mostly within the reference ranges. Although a CT-guided needle biopsy was performed, histologic diagnosis could not be confirmed. We resected the tumor with the thymus by median sternotomy. Histopathological examination demonstrated that the tumor was a multilocular thymic cyst with thymic hyperplasia and numerous lymphocytes. The lining epithelial cells gave positive reactions to immunohistochemical staining for carbohydrate antigen 19-9. Carcinoembryonic antigen and squamous cell carcinoma antigen levels in the cystic fluid were elevated. This case appeared to be an acquired thymic cyst with thymic hyperplasia. There are few reports of such cysts.     

Secure and effective gene delivery system of plasmid DNA coated by polynucleotide

Polynucleotides are anionic macromolecules which are expected to transfer into the targeted cells through specific uptake mechanisms. So, we developed polynucleotides coating complexes of plasmid DNA (pDNA) and polyethylenimine (PEI) for a secure and efficient gene delivery system and evaluated their usefulness. Polyadenylic acid (polyA), polyuridylic acid (polyU), polycytidylic acid (polyC), and polyguanylic acid (polyG) were examined as the coating materials. pDNA/PEI/polyA, pDNA/PEI/polyU, and pDNA/PEI/polyC complexes formed nanoparticles with a negative surface charge although pDNA/PEI/polyG was aggregated. The pDNA/PEI/polyC complex showed high transgene efficiency in B16-F10 cells although there was little efficiency in pDNA/PEI/polyA and pDNA/PEI/polyU complexes. An inhibition study strongly indicated the specific uptake mechanism of pDNA/PEI/polyC complex. Polynucleotide coating complexes had lower cytotoxicity than pDNA/PEI complex. The pDNA/PEI/polyC complex showed high gene expression selectively in the spleen after intravenous injection into mice. The pDNA/PEI/polyC complex showed no agglutination with erythrocytes and no acute toxicity although these were observed in pDNA/PEI complex. Thus, we developed polynucleotide coating complexes as novel vectors for clinical gene therapy, and the pDNA/PEI/polyC complex as a useful candidate for a gene delivery system.     

Dendritic cell SIRPα regulates homeostasis of dendritic cells in lymphoid organs

Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is expressed predominantly in myeloid lineage cells such as dendritic cells (DCs) or macrophages, mediates cell–cell signaling. In the immune system, SIRPα is thought to be important for homeostasis of DCs, but it remains unclear whether SIRPα intrinsic to DCs is indeed indispensable for such functional role. Thus, we here generated the mice, in which SIRPα was specifically ablated in CD11c⁺ DCs (Sirpa^ΔDC). Sirpa^ΔDC mice manifested a marked reduction of CD4⁺ CD8α^– conventional DCs (cDCs) in the secondary lymphoid organs, as well as of Langerhans cells in the epidermis. Such reduction of cDCs in Sirpa^ΔDC mice was comparable to that apparent with the mice, in which SIRPα was systemically ablated. Expression of SIRPα in DCs was well correlated with that of either endothelial cell‐selective adhesion molecule (ESAM) or Epstein–Barr virus‐induced molecule 2 (EBI2), both of which were also implicated in the regulation of DC homeostasis. Indeed, ESAM⁺ or EBI2⁺ cDCs were markedly reduced in the spleen of Sirpa^ΔDC mice. Thus, our results suggest that SIRPα intrinsic to CD11c⁺ DCs is essential for homeostasis of cDCs in the secondary lymphoid organs and skin.     

Modulation of TNFR 1-triggered two opposing signals for inflammation and apoptosis via RIPK 1 disruption by geldanamycin in rheumatoid arthritis

Clinical Rheumatology - To evaluate the ability of geldanamycin to modulate two opposing TNFα/TNFR1-triggered signals for inflammation and cell death. The effects of geldanamycin on...     

Increased DNA-incorporated thiopurine metabolite as a possible mechanism for leukocytopenia through cell apoptosis in inflammatory bowel disease patients with NUDT15 mutation

Journal of Gastroenterology - Polymorphisms in the nucleotide diphosphate-linked moiety X-type motif 15 (NUDT15) gene are associated with thiopurine-induced leukopenia in patients with inflammatory...     

Hepatic natural killer and natural killer T cells markedly decreased in two cases of drug-induced fulminant hepatic failure rescued by living donor liver transplantation

The human liver contains significant numbers of innate immune cells, such as natural killer (NK) cells and natural killer T (NKT) cells, which express both T-cell receptors and NK-cell receptors simultaneously. It has been suggested that the innate immune system plays a crucial role in the liver. In this report, the distribution of NK and NKT cells in the liver and peripheral blood of two patients with drug-induced fulminant hepatic failure (FHF) who had undergone living donor liver transplantation was examined. In both the liver and peripheral blood, the proportions of NK and NKT cells markedly decreased compared with those in healthy donors. It was also revealed that, unlike murine NKT cells, human CD56(+) T cells and CD57(+) T cells did not constitutively express CD28, which is one of the important costimulatory molecules on T cells. Additionally, the residual CD56(+) T cells and CD57(+) T cells in the patients expressed more CD28 than in controls. This result suggests that NKT cells might be more activated in FHF. Although the accumulation of further cases is required, it is suggested that both NK and NKT cells might be involved in hepatic injury in FHF.     

Lipopolysaccharide‐induced cytokine and receptor expression and neutrophil infiltration in the liver of osteopetrosis (op/op) mutant mice

Abstract: Background/Aims: Mice homozygous for the osteopetrosis (op) mutation are genetically deficient in macrophage colony‐stimulating factor (M‐CSF/CSF‐1) and are characterized by defective differentiation and function of macrophages. The aim of this study is to assess the contribution of M‐CSF to lipopolysaccharide (LPS)‐induced cytokine expression and neutrophil infiltration in the liver. Methods: We investigated the effects of LPS administration in M‐CSF‐deficient op/op mutant mice. The expression of cytokines and receptors in the liver was studied by immunohistochemistry and RT‐PCR. Neutrophil infiltration in the liver was also examined. Results: After LPS administration, cytokine production and expression of LPS receptors, such as CD14 and scavenger receptor class A (MSR‐A), were induced at lower levels in op/op mice than those in littermate mice. Neutrophil infiltration in the liver of op/op mice did not differ significantly from that of littermate mice. Anti‐IL‐8 receptor homologue and anti‐C5a receptor antibody reduced the number of infiltrating neutrophils. Conclusions: These findings indicate that deficient macrophage activation following LPS injection in op/op mice is associated with decreased expression of CD14 and MSR‐A in the liver. Thus, M‐CSF plays a critical role in LPS‐induced macrophage activation but does not exert a dominant role in neutrophil infiltration in the liver.