A Case of Metastatic Urachal Cancer Including a Neuroendocrine Component Treated with Gemcitabine, Cisplatin and Paclitaxel Combination Chemotherapy.

The present case report describes a case of recurrent and advanced urachal carcinoma including neuroendocrine features with iliac bone metastasis after partial cystectomy and adjuvant chemotherapy consisting of irinotecan and cisplatin in a 32-year-old man. He received gemcitabine/cisplatin/ paclitaxel (GCP) combination chemotherapy, consisting of gemcitabin (1,000mg/m2) on day 1, 8, cisplatin (70mg/m2) on day 1, and paclitaxel (80mg/m2) on day 1 and 8. After three cycles of chemotherapy, PET-CT showed complete regression of the disease.

Effectiveness and Safety of Ureteroscopic Holmium Laser Lithotripsy for Upper Urinary Tract Calculi in Elderly Patients.

Upper urinary tract calculi are common; however, there is no recommended treatment selection for elderly patients. Ureteroscopic holmium laser lithotripsy (URS lithotripsy) is minimally invasive, and it provides a high stone-free rate (SFR) treatment for upper urinary tract calculi. Here, we retrospectively evaluated the surgical outcomes of URS lithotripsy after dividing the 189 cases into 3 groups by patient age: the '＜65 group' (＜65 years old, n＝108), the '65-74 group' (65-74 years old, n＝42), and the ' 75 group' ( 75 years old, n＝39).

[The effects of TGF-βs on immune responses].

Transforming growth factor (TGF)-β family is a cytokine family with various biological processes and forms a highly homologous group of three mammalian isoforms, TGF-β1, TGF-β2, and TGF-β3. Most of the attention on TGF-β family in immunology has been mainly focused on TGF-β1 in that TGF-β1 induces anti-inflammatory regulatory T cells (Treg), and inflammatory T helper 17 (Th17) cells in combination with interleukin-6. Although little attention has been focused on the immunological roles of TGF-β2 and TGF-β3, the function of TGF-β3 for maintaining immunological homeostasis has recently been identified such as the induction of Th17 cells and direct regulatory effects on humoral immunity.

[Autoimmune disease and epigenome regulation].

Epigenetic modifications play a central role in the cellular programming of gene expression. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Recent observation that a number of GWAS SNP for immunological diseases localize to immune enhancers suggests the importance of epigenetic modifications that control enhancer activity.

Decreased severity of experimental autoimmune arthritis in peptidylarginine deiminase type 4 knockout mice.

Background: Peptidylarginine deiminase type 4 (PADI4) has been identified as a susceptibility gene for rheumatoid arthritis (RA) by genome-wide association studies. PADI4 is highly expressed in the bone marrow, macrophages, neutrophils, and monocytes. Peptidyl citrulline is an interesting molecule in RA because it is a target antigen for anti-citrullinated peptide antibodies, and only PADs (translated proteins from PADI genes) can provide peptidyl citrulline via the modification of protein substrates.

Efficacy of intensive immunosuppression in exacerbated rheumatoid arthritis-associated interstitial lung disease.

Objectives: Acute or subacute exacerbations are recognized as a severe complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Nevertheless, the role of intensive immunosuppression in RA-ILD remains elusive. We attempted to evaluate the clinical characteristics and efficacy of immunosuppressive treatment in exacerbated RA-ILD.

Thoracic intradural extramedullary lesions causing progressive myelopathy as an initial manifestation of granulomatosis with polyangiitis: a case report and review of literature.

Context: To our knowledge, only a few reports regarding the spinal involvement of granulomatosis with polyangiitis (GPA)-also termed as Wegener's granulomatosis-have been published. However, all these cases reportedly exhibited epidural tumor-like lesions or dural thickening.

Findings: We report the case of a 57-year-old woman with progressive myelopathy caused by multiple spinal lesions with GPA, which appeared to be protruding inwards, within the dura mater, on magnetic resonance imaging (MRI); these lesions were difficult to distinguish from intradural tumors.

Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis.

Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model.

Immune responses to Mycobacterial heat shock protein 70 accompany self-reactivity to human BiP in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease, and a member of human heat shock protein (HSP) 70 protein family, Binding Immunoglobulin Protein (BiP), has been identified as an important autoantigen for T and B cells. We herein focused on Mycobacterial (Myc) HSPs and immune responses to MycHSPs in RA patients. Serum titers of antibodies against MycHSP70 were significantly elevated in RA patients and correlated with serum anti-BiP antibody titers.

Calcium Phosphate Composition Affects Ureteroscopic Laser Lithotripsy.

The effects of stone composition on transurethral lithotripsy (TUL) have not been sufficiently elucidated. The purpose of this study was to identify how calcium phosphate stone composition impacts TUL. Two hundred eighty-nine cases of semi-rigid and/or flexible TUL for upper urinary tract calculi were reviewed retrospectively.

Effects of Added Salts on Surface Tension and Aggregation of Crown Ether Surfactants.

Two crown ether surfactants, dodecanoyloxymethyl- (C11Φ6) and octanoyloxymethyl-18-crown-6 (C7Φ6), were synthesized and the surface tension dependence on surfactant concentration of their aqueous solutions was measured both in the absence and presence of alkali chlorides to confirm the critical micelle concentration (CMC) is highest for the added cation that have an ionic diameter comparable to the hole size of the crown ether ring and that several break points on the surface tension vs. concentration curves occur for these crown ether surfactants. For C11Φ6 and C7Φ6, in the absence of salt, the surface tension vs.

Therapeutic potential of regulatory cytokines that target B cells.

Autoreactive B cells play a crucial role in the pathogenesis of autoimmune diseases by producing auto-antibodies and presenting antigens. Regulatory cytokines that simultaneously suppress multiple pathways have the potential to control autoreactive B cells. The generally inhibitory cytokine IL-10 may have a stimulatory effect on human B-cell survival and antibody production.

Role of TGF-β3 in the regulation of immune responses.

Transforming growth factor-betas (TGF-βs) are multifunctional cytokines that have been implicated in the regulation of a broad range of biological processes, including cell proliferation, cell survival, and cell differentiation. The three isoforms identified in mammals, TGF-β1, TGF-β2, and TGF-β3, have high sequence homology, bind to the same receptors, and show similar biological functions in many in vitro studies. However, analysis of the in vivo functions of the three isoforms and mice deficient for each cytokine reveals striking differences, illustrating their unique biological importance and functional non-redundancy.

Peptidylarginine deiminase type 4 deficiency reduced arthritis severity in a glucose-6-phosphate isomerase-induced arthritis model.

Peptidyl arginine deiminase 4 (PAD4) is an enzyme that is involved in protein citrullination, and is a target for anti-citrullinated peptide antibodies (ACPAs) in rheumatoid arthritis (RA). Genetic polymorphisms in the PADI4 gene encoding PAD4 are associated with RA susceptibility. We herein analyzed the roles of PADI4 in inflammatory arthritis using a glucose-6-phosphate isomerase (GPI)-induced arthritis (GIA) model in Padi4 knockout (KO) mice.

Quantitative and qualitative characterization of expanded CD4+ T cell clones in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is an autoimmune destructive arthritis associated with CD4(+) T cell-mediated immunity. Although expanded CD4(+) T cell clones (ECs) has already been confirmed, the detailed characteristics of ECs have not been elucidated in RA. Using combination of a single-cell analysis and next-generation sequencing (NGS) in TCR repertoire analysis, we here revealed the detailed nature of ECs by examining peripheral blood (PB) from 5 RA patients and synovium from 1 RA patient.

Quantitative Measurement of GPCR Endocytosis via Pulse-Chase Covalent Labeling.

G protein-coupled receptors (GPCRs) play a critical role in many physiological systems and represent one of the largest families of signal-transducing receptors. The number of GPCRs at the cell surface regulates cellular responsiveness to their cognate ligands, and the number of GPCRs, in turn, is dynamically controlled by receptor endocytosis. Recent studies have demonstrated that GPCR endocytosis, in addition to affecting receptor desensitization and resensitization, contributes to acute G protein-mediated signaling.

Decisive interactions between the heterocyclic moiety and the cluster observed in polyoxometalate-surfactant hybrid crystals.

Inorganic-organic hybrid crystals were successfully obtained as single crystals by using polyoxotungstate anion and cationic dodecylpyridazinium (C12pda) and dodecylpyridinium (C12py) surfactants. The decatungstate (W10) anion was used as the inorganic component, and the crystal structures were compared. In the crystal comprising C12pda (C12pda-W10), the heterocyclic moiety directly interacted with W10, which contributed to a build-up of the crystal structure.

Autoantigen BiP-Derived HLA-DR4 Epitopes Differentially Recognized by Effector and Regulatory T Cells in Rheumatoid Arthritis.

Objective: The balance between effector and regulatory CD4+ T cells plays a key role in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to examine whether the RA autoantigen BiP has epitopes for both effector and regulatory immunities.

Methods: The proliferation and cytokine secretion of peripheral blood mononuclear cells (PBMCs) from HLA-DR4-positive RA patients in response to BiP-derived peptides were examined by (3)H-thymidine uptake and enzyme-linked immunosorbent assay.

[Regulatory T cells in systemic lupus erythematosus].

Autoantibodies are associated with various autoimmune diseases. Systemic lupus erythematosus (SLE) is an autoantibody-associated autoimmune disease which affects multiple organs. Although both genetic and environmental factors are implicated in lupus pathogenesis, the etiology of the disease remains elusive.

TGF-β3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses.

Autoantibodies induce various autoimmune diseases, including systemic lupus erythematosus (SLE). We previously described that CD4(+)CD25(-)LAG3(+) regulatory T cells (LAG3(+) Treg) are regulated by Egr2, a zinc-finger transcription factor required for the induction of T-cell anergy. We herein demonstrate that LAG3(+) Treg produce high amounts of TGF-β3 in an Egr2- and Fas-dependent manner.