Stent-retriever characteristics and strategies associated with recanalization in thrombectomy for acute ischemic stroke.

INTRODUCTION: Predictive factors for successful reperfusion in mechanical thrombectomy for acute ischemic stroke, and especially technical factors, remain controversial. We investigated various techniques for better angiographic outcomes. METHODS: In this retrospective study, acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy with combined technique were included. Scoring of the reperfusion grade for each attempt was conducted, and each attempt was divided into two groups based on successful reperfusion, which was defined using the presence or absence of modified thrombolysis in cerebral infarction 2b-3. The following characteristics were evaluated: the choice of stent-retriever, its length, occlusion site, thrombus position relative to deployed stent-retriever, methods of thrombectomy, and successful advancement of the distal access catheter to the proximal end of the thrombus. RESULTS: Among 251 patients who underwent mechanical thrombectomy, 154 patients (255 attempts: mTICI 0-2a group, n = 119; mTICI 2b-3 group, n = 136) were included in the analysis. The thrombus position relative to the deployed stent-retriever was likely associated with successful reperfusion, although it was not statistically significant (proximal two-thirds 56.8 %; distal one-third 44.3 %, p = 0.09). Successful advancement of the distal access catheter was related to successful reperfusion both in univariate analysis (success 57.9 %; fail 35.8 %, p < 0.01) and in multivariate regression analysis (odds ratio 2.45; 95 % confidence interval: 1.30-4.61, p < 0.01). CONCLUSIONS: Successful advancement of the distal access catheter to the proximal end of thrombus might be a key component for successful reperfusion in mechanical thrombectomy.

Clinicopathological comparison between PTCL-TBX21 and PTCL-GATA3 in Japanese patients.

AIM: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is a heterogeneous disease that can be classified into the PTCL-TBX21 and PTCL-GATA3 subtypes. METHODS: In this study, we compared the clinicopathological features of PTCL-NOS in a Japanese cohort, classified using an IHC algorithm. RESULTS: One hundred patients with PTCL-NOS were categorized as having PTCL-TBX21 (n = 55), PTCL-GATA3 (n = 24), or PTCL-unclassified (n = 21). When comparing PTCL-TBX21 and PTCL-GATA3, PTCL-TBX21 showed significantly lower CD4 positivity (p = 0.047), lower counts of high endothelial venules (p = 0.032), and a tendency for a better response to initial treatment (p = 0.088). Gene expression analysis using the nCounter system showed higher expression of tumor immunity-related genes, such as PD-L1, LAG3, and IDO1, in PTCL-TBX21 than in PTCL-GATA3. PTCL-GATA3 had significantly worse overall survival (OS) than those with PTCL-TBX21 (p = 0.047), although a similar tendency was observed for progression-free survival (PFS) (p = 0.064). PTCL-GATA3 was a prognostic factor for OS in univariate analysis (HR 2.02; 95% CI, 1.09-3.77; p = 0.027), although multivariate analysis did not show significance (HR 2.07; 95% CI, 0.93-4.61; p = 0.074). In the PFS analysis, PTCL-GATA3 was an independent prognostic factor by univariate analysis (HR 1.96; 95% CI, 1.08-3.56; p = 0.027) and multivariate analysis (HR 2.34; 95% CI, 1.07-5.11; p = 0.032). CONCLUSION: The classification of PTCL-NOS into PTCL-TBX21 and PTCL-GATA3 is useful for predicting the prognosis of Japanese patients and stratifying the administration of tumor immune checkpoint inhibitors in clinical practice.

Co-expression of regulatory B-cell markers, transforming growth factor ß and interleukin-10 as a prognostic factor in diffuse large B-cell lymphoma.

Regulatory B cells (Bregs) suppress antitumor immunity by producing anti-inflammatory cytokines such as transforming growth factor ß (TGF-ß) and interleukin-10 (IL-10) and promoting tumor growth. It is unknown whether diffuse large B-cell lymphoma (DLBCL), a common subtype of B-cell malignancy, exhibits characteristics similar to those of Bregs. This study aimed to clarify the features of DLBCLs carrying Breg markers. In 123 DLBCL cases, we evaluated TGF-ß and IL-10 expression in tumor biopsy samples using immunohistochemical staining and retrospectively analyzed their clinicopathological characteristics. Fifteen cases (12.2 %) classified as Breg-type DLBCL were positive for both TGF-ß and IL-10. Breg-type DLBCL is mainly classified as having activated B cell-like cells of origin. Breg-type DLBCL cases showed significantly worse progression-free survival and overall survival (OS) than other DLBCL cases (P = 0.0016 and P = 0.042, respectively). In multivariate analysis, Breg-type DLBCL significantly affected OS (hazard ratio, 3.13; 95 % confidence interval 1.15-8.55; P = 0.025). Gene expression analysis showed that the expression of follicular dendritic cell-associated genes (FCER2, PIK3CD, FOXO1) was downregulated in Breg-type DLBCLs compared to other DLBCLs. These results suggest that the double expression of Breg markers, TGF-ß and IL-10, in tumor cells indicates a poor prognosis in DLBCL patients. Further studies evaluating genomic abnormalities could confirm the characteristics of Breg-type DLBCL.

Clinicopathological analysis of CD47 and signal regulatory protein alpha expression in myeloid sarcoma patients: CD47 expression is a favourable prognostic factor.

Myeloid sarcoma is a rare extramedullary haematopoietic malignancy. Interaction between CD47 and signal regulatory protein α (SIRPα) inhibits phagocytosis. CD47-positive tumours confer poor prognoses in various malignant tumours, including acute myeloid leukaemia. This study aimed to investigate the clinicopathological effects of CD47 and SIRPα expression in myeloid sarcoma. Immunohistochemistry (IHC) of CD47 and SIRPα was performed in 84 biopsy samples obtained from patients with myeloid sarcoma, some of which were CD47-positive. Patients were categorised into the following two groups based on IHC of SIRPα: those with SIRPα-positive neoplastic cells (nSIRPα) and, SIRPα expression on non-neoplastic stromal cells in tumour microenvironment (miSIRPα). In addition, patients with CD47 positivity had higher lymphocytic infiltration into the tumour microenvironment. Overall, these patients had significantly higher overall survival, however, no significant difference was observed in progression-free survival. No significant prognostic differences were observed between the nSIRPα and miSIRPα groups. This is the first study to demonstrate an association between CD47 expression and improved prognosis in myeloid sarcoma. Nonetheless, it will be necessary to conduct additional research on gene expression and genomic abnormalities to elucidate the corresponding pathogenesis of myeloid sarcoma.

Case-based similar image retrieval for weakly annotated large histopathological images of malignant lymphoma using deep metric learning.

In the present study, we propose a novel case-based similar image retrieval (SIR) method for hematoxylin and eosin (H&E) stained histopathological images of malignant lymphoma. When a whole slide image (WSI) is used as an input query, it is desirable to be able to retrieve similar cases by focusing on image patches in pathologically important regions such as tumor cells. To address this problem, we employ attention-based multiple instance learning, which enables us to focus on tumor-specific regions when the similarity between cases is computed. Moreover, we employ contrastive distance metric learning to incorporate immunohistochemical (IHC) staining patterns as useful supervised information for defining appropriate similarity between heterogeneous malignant lymphoma cases. In the experiment with 249 malignant lymphoma patients, we confirmed that the proposed method exhibited higher evaluation measures than the baseline case-based SIR methods. Furthermore, the subjective evaluation by pathologists revealed that our similarity measure using IHC staining patterns is appropriate for representing the similarity of H&E stained tissue images for malignant lymphoma.

Direct observation of Mn distribution/speciation within and surrounding a basidiomycete fungus in the production of Mn-oxides important in toxic element containment.

Biogenic manganese (Mn) oxides occur ubiquitously in the environment including the uranium (U) mill tailings at the Ningyo-toge U mine in Okayama, Japan, being important in the sequestration of radioactive radium. To understand the nanoscale processes in Mn oxides formation at the U mill tailings site, Mn2+ absorption by a basidiomycete fungus, Coprinopsis urticicola, isolated from Ningyo-toge mine water samples, was investigated in the laboratory under controlled conditions utilizing electron microscopy, synchrotron-based X-ray analysis, and fluorescence microscopy with a molecular pH probe. The fungus' growth was first investigated in an agar-solidified medium supplemented with 1.0 mmol/L Mn2+, and Cu2+ (0-200 µM), Zn2+ (0-200 µM), or diphenyleneiodonium (DPI) chloride (0-100 µM) at 25 °C. The results revealed that Zn2+ has no significant effects on Mn oxide formation, whereas Cu2+ and DPI significantly inhibit both fungal growth and Mn oxidation, indicating superoxide-mediated Mn oxidation. Indeed, nitroblue tetrazolium and diaminobenzidine assays on the growing fungus revealed the production of superoxide and peroxide. During the interaction of Mn2+ with the fungus in solution medium at the initial pH of 5.67, a small fraction of Mn2+ infiltrated the fungal hyphae within 8 h, forming a few tens of nm-sized concentrates of soluble Mn2+ in the intracellular pH of ∼6.5. After 1 day of incubation, Mn oxides began to precipitate on the hyphae, which were characterized as fibrous nanocrystals with a hexagonal birnessite-structure, these forming spherical aggregates with a diameter of ∼1.5 µm. These nanoscale processes associated with the fungal species derived from the Ningyo-toge mine area provide additional insights into the existing mechanisms of Mn oxidation by filamentous fungi at other U mill tailings sites under circumneutral pH conditions. Such processes add to the class of reactions important to the sequestration of toxic elements.

Clinicopathological analysis of immunohistochemical expression of immune checkpoint molecules in follicular lymphoma.

Follicular lymphoma (FL) is characterized by an indolent clinical course and a high relapse rate, and often exhibits a diffuse pattern beyond the follicular area. Our group previously reported that immune checkpoint (ICP) pathways, such as programmed cell death (PD-1) and programmed death ligand 1 (PD-L1), are poor prognostic factors for diffuse large B-cell lymphoma and adult T-cell leukemia/lymphoma. In this study, the association between the expression of multiple ICP molecules according to immunohistochemistry and clinicopathological features in FL was determined via immunostaining of 173 biopsy samples. Membrane and/or cytoplasm expression of CD86 (nCD86) and PD-L1 (nPD-L1) was found in tumor cells, whereas PD-1 (miPD-1), Galectin-9 (miGalectin-9), OX40 (miOX40), CTLA-4 (miCTLA-4), Tim-3 (miTim-3), OX40L (miOX40L), and LAG-3 (miLAG-3) were expressed in non-neoplastic stromal cells. MiPD-1 expression was significantly higher in the follicular area than in the diffuse area (p = 0.0450). Expression of miOX40 and miCTLA-4 was significantly higher in the diffuse area than in the follicular area (respectively, p = 0.0053 and p = 0.0092). MiTim-3 tended to be higher in the diffuse area than in the follicular area (p = 0.0616). MiTim-3 was significantly higher in relapse cases than in new-onset cases (p = 0.0440); miLAG-3 tended to be higher in relapse cases than in new-onset cases (p = 0.0622, not significant). The miOX40L-high FL group had a significantly worse overall survival than the miOX40L-low group (p = 0.0320). The expression of multiple ICP molecules on several cells reflects activated anti-tumor immunity and the unique FL microenvironment. Further studies on gene expression or genomic abnormalities will reveal the clinical and biological significance of ICP molecules in FL.

Clinicopathological analysis of myeloid sarcoma with megakaryocytic differentiation.

Myeloid sarcoma (MS) is defined as a tumour mass consisting of myeloid blasts that occurs at an anatomical site other than bone marrow. MS with megakaryocytic differentiation (MSmgk) is extremely rare and its clinicopathological features have not been well described. We reviewed 11 cases in 11 patients of extramedullary mass-forming malignant tumours composed of immature non-lymphoid haematopoietic cells expressing CD41 with or without concurrent bone marrow lesions. The patients consisted of seven men and four women (1.75:1 male-to-female ratio). The mean and median ages at diagnosis were 50 and 62 years, respectively, ranging from 2 to 78 years. Extramedullary mass lesions were solitary in three cases (27%) and multiple in eight cases (73%). Tumour locations were lymph nodes (6 cases), subcutaneous tissue (3 cases), intramuscular (1 case), and bone (1 case). Seven of the 11 patients (64%) had a history of myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN). Three patients (27%) developed MS during remissions of acute myelogenous leukaemia, and one patient had a recurrence of MS at other sites. Follow-up data were available for four cases. Tumour cells were positive for CD41, CD33, CD34, MPO, and CD68 in 11 (100%), three (27%), seven (64%), four (36%), and seven (64%) cases, respectively. Cytogenetic analysis was successfully performed in two cases. Complex but inconsistent abnormalities were evident. When compared with cases of MS without megakaryocytic differentiation, the survival of MSmgk was significantly shorter (p=0.0033). Compared to MS without megakaryocytic differentiation, MSmgk is more likely to follow MDS/MPN, to involve multiple sites, and to be associated with poorer outcomes. More detailed studies, including genomic or gene expression analyses, could confirm the characteristics of MSmgk.

DA-EPOCH-R therapy for high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements in a patient with renal dysfunction.

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, also known as double-hit lymphoma, has been reported as refractory to R-CHOP therapy and requires more intensive regimens. However, intensive and safe regimens for patients with renal dysfunction are unknown. Herein, we report the successful use of DA-EPOCH-R therapy for double-hit lymphoma in a 64-year-old man with renal dysfunction. The patient had lymphoma-induced bilateral ureteral obstruction. Although renal dysfunction remained after removing the obstruction using R-CHOP therapy, we completed six cycles of DA-EPOCH-R therapy without any major adverse events. DA-EPOCH-R therapy may be a safe regimen for renal dysfunction patients.

Autoimmune myelofibrosis associated with systemic lupus erythematosus: a case report.

A 66-year-old woman presented with severe anaemia, thrombocytopenia and lymphopenia. The bone marrow biopsy demonstrated hypocellular marrow with myelofibrosis (MF); there was no evidence of malignancy, but infiltration of peripheral T and B cells were noticed. Magnetic resonance imaging (MRI) revealed that bone marrow of the spine exhibited low signal intensity (SI) with spotty high SI in T1- and T2-weighted images. Because there was evidence of autoimmune abnormality, she had fulfilled the classification criteria for systemic lupus erythematosus (SLE). She was diagnosed with autoimmune myelofibrosis (AIMF) associated with SLE and was treated with corticosteroid. Cytopenia improved after 1 month of corticosteroid therapy. A repeated bone marrow biopsy demonstrated that cellularity had increased and that the amount of reticulin fibre had reduced after treatment. Compared with primary MF, AIMF has generally a favourable prognosis and is often associated with autoimmune diseases, especially SLE. Bone marrow biopsy, but not aspiration, was useful for diagnosing bone marrow fibrosis. Although the association between SLE and MF has been rarely reported, we should pay attention to MF as a possible cause of pancytopenia.

Cytokine-related genes play critical roles in extrafollicular growth of follicular lymphoma cells.

Follicular lymphoma (FL) is a germinal center-derived B-cell lymphoma that is known to proliferate in the intrafollicular region. However, lymphoma cells can be identified in the extrafollicular regions, which are related to disease dissemination. We purified the intrafollicular and extrafollicular regions of FL cells by laser microdissection and conducted microarray analysis in order to characterize the gene expression profiles of FL cells from both regions. BCL2 and genes of germinal B-cell markers clearly separated intrafollicular and extrafollicular regions of reactive follicular hyperplasia, suggesting the adequacy of the current analysis. In FL cases, cytokine-related genes were significantly enriched in extrafollicular regions compared with those in the intrafollicular regions. In intrafollicular regions of FL, cell-cycle-related genes were enriched. We found that the FL cells in the extrafollicular region more strongly expressed IL3RA and CXCL12 than those of intrafollicular regions. The cytokines might be also derived from stroma cells in the extrafollicular regions, which may initiate activation and migration of the tumor cells to this region. Our results suggest that FL cell interaction with surrounding stroma cells plays an important role in the pathophysiology of FL and that such interactions should be a good target for therapy.

Combination of CD47 and signal-regulatory protein-α constituting the "don't eat me signal" is a prognostic factor in diffuse large B-cell lymphoma.

The interaction between CD47 and signal-regulatory protein-α (SIRPα) inhibits phagocytosis, thus affecting the clinical outcomes of neoplastic diseases. Although CD47 upregulation is associated with poor prognosis in several malignancies, the effect of SIRPα expression and its coexpression with CD47 remains unclear. This study aimed to investigate the clinicopathologic effect of CD47 and SIRPα expression in diffuse large B-cell lymphoma (DLBCL). Immunostaining of 120 biopsy samples showed that CD47 is primarily expressed in tumor cells, whereas SIRPα is expressed in nonneoplastic stromal cells, mostly macrophages. CD47high cases showed higher MYC protein expression and lower MYC translocation. The SIRPαhigh cases presented significantly shorter overall survival (OS) and progression-free survival (PFS) than SIRPαlow cases in the activated B-cell (ABC) subtype of DLBCL (P = .04 and P = .02, respectively). Both CD47high and SIRPαhigh presented significantly shorter OS and PFS than other cases among all DLBCL patients (P = .01 and P = .004, respectively), and the ABC type (P = .04 and P = .008, respectively) but not the germinal center B-cell type. Both CD47high and SIRPαhigh yielded a constant independent prognostic value for OS and PFS in multivariate analysis (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.20-7.43; P = .02; and HR, 2.87; 95% CI, 1.42-5.85; P = .003, respectively). To the best of our knowledge, this is the first study to report that combinatorial CD47 and SIRPα expression is a potential independent prognostic factor for DLBCL. Evaluation of CD47 and SIRPα expression could be useful before CD47 blockade therapy.

Comprehensive immunohistochemical analysis of immune checkpoint molecules in adult T cell leukemia/lymphoma.

Acute or lymphomatous type adult T cell leukemia/lymphoma (ATLL) is an aggressive hematopoietic malignancy with poor prognosis. We previously reported that programmed cell death ligand 1 (PD-L1) expression could predict ATLL outcomes. However, the roles of other immune checkpoint molecules remain largely unknown in ATLL. Our aim in this study was to explore the clinicopathological impacts of immune checkpoint molecules in ATLL. Immunohistochemistry was performed in 69 ATLL patients with antibodies against the following: PD-L1, programmed cell death ligand 2 (PD-L2), OX40, OX40 ligand (OX40L), CD137, CD137 ligand (CD137L), Galectin-9, T cell immunoglobulin mucin-3 (Tim-3), cytotoxic T lymphocyte associated protein-4 (CTLA-4), lymphocyte activating-3 (LAG-3), CD80, CD86, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), GITR ligand (GITRL), and programmed death-1 (PD-1). Immune checkpoint molecules were variably expressed on neoplastic and/or microenvironmental cells. Expression of PD-1, OX40L, Galectin-9, and PD-L1 was nearly mutually exclusive on neoplastic cells, suggesting that immune checkpoint pathways differ in patients. Microenvironmental expression of PD-L1, OX40L, and Tim-3 was significantly associated with better overall survival (log-rank test; P =0.0004, 0.0394, and 0.0279, respectively). Univariate and multivariate analyses with clinical prognostic factors identified microenvironmental expression of PD-L1 and OX40L, and age (> 70 years) as significant prognostic factors. This is the first comprehensive analysis of ATLL immune checkpoint molecules. Our results may provide information on new therapeutic strategies in ATLL.

Clinicopathological analysis of splenic red pulp low-grade B-cell lymphoma.

Primary splenic low-grade B-cell lymphoma of the red pulp comprises hairy cell leukemia (HCL) and splenic B-cell lymphoma/leukemia, unclassifiable (SPLL-U). SPLL-U is a rare disease that includes subtypes of a hairy cell leukemia-variant (HCL-v), splenic diffuse red pulp small B-cell lymphoma (SDRPL) and other types that are known as narrow sense SPLL-U (SPLL-U-NS). Notably, limited information is available regarding the BRAF mutation (V600E) and cyclin D3 expression in subtypes of SPLL-U. Therefore, we performed a pathological analysis of the BRAF mutation (V600E) and characterized pathological features of SPLL-U. We reviewed the pathological findings of 12 SPLL-U cases. The 12 cases considered included two cases of HCL-v, six cases of SPLL-U-NS and four undetermined cases. The BRAF mutation (V600E) was detected in three cases, which were all SPLL-U-NS. Cases with the BRAF mutation (V600E) have increased levels of CD103 expression and decreased cyclin D3 and cyclin D1 expression compared with cases that lacked the BRAF mutation. These findings suggest that the BRAF mutation might play a significant role in SPLL-U. Therefore, the significance of the BRAF mutation should be evaluated via genomic or transcriptional analyses of a large cohort of SPLL-U patients.

High-fat diets provoke phosphorus absorption from the small intestine in rats.

OBJECTIVE: The ratio of dietary carbohydrate to fat may affect phosphorus metabolism because both calcium and phosphorus are regulated by similar metabolic mechanisms, and a high-fat diet (HFD) induces deleterious effects on the absorption of dietary calcium. We hypothesized that an HFD induces an increase in phosphorus absorption. The aim of this study was to evaluate the effects of differences in the quantity and quality of dietary fat on phosphorus metabolism over the short- and long-term. METHODS: Eighteen 8-wk-old Sprague-Dawley male rats were fed an isocaloric diet containing varied ratios of carbohydrates to fat energy and sources of fat (control diet, HFD, and high- saturated fat diet [HF-SFA]). At 3 d and 7 wk after the allocation and initiation of the test diets, feces and urine were collected and used for phosphorus and calcium measurement. RESULTS: The fecal phosphorous concentration (F-Pi) was lower in the HF-SFA group than in the other two groups; however, the urine phosphorus concentration (U-Pi) was significantly higher in the HF-SFA group than the other two groups when the rats were fed over the short- (P < 0.01) and long -term (P < 0.01 versus control, P < 0.05 versus HFD group). There were no significant differences in type-IIa sodium-phosphate cotransporter (NaPi-2 a) and type-IIc sodium-phosphate cotransporter (NaPi-2 c) mRNA expression, which are renal phosphate transport-related genes; however, the expression of type-IIb sodium-phosphate cotransporter (NaPi-2 b) and type-III sodium-phosphate cotransporter (Pit-1) mRNA in the duodenum was higher in the HFD and HF-SFA groups than in the control group (P < 0.05), although there were no significant differences in these in the jejunum. CONCLUSIONS: The present results indicated that an HFD, particularly HF-SFA, increases intestinal phosphate absorption compared with control.

Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population.

OBJECTIVE: The causality and pathogenic mechanism of microbiome composition remain elusive in many diseases, including autoimmune diseases such as rheumatoid arthritis (RA). This study aimed to elucidate gut microbiome's role in RA pathology by a comprehensive metagenome-wide association study (MWAS). METHODS: We conducted MWAS of the RA gut microbiome in the Japanese population (ncase=82, ncontrol=42) by using whole-genome shotgun sequencing of high depth (average 13 Gb per sample). Our MWAS consisted of three major bioinformatic analytic pipelines (phylogenetic analysis, functional gene analysis and pathway analysis). RESULTS: Phylogenetic case-control association tests showed high abundance of multiple species belonging to the genus Prevotella (e.g., Prevotella denticola) in the RA case metagenome. The non-linear machine learning method efficiently deconvoluted the case-control phylogenetic discrepancy. Gene functional assessments showed that the abundance of one redox reaction-related gene (R6FCZ7) was significantly decreased in the RA metagenome compared with controls. A variety of biological pathways including those related to metabolism (e.g., fatty acid biosynthesis and glycosaminoglycan degradation) were enriched in the case-control comparison. A population-specific link between the metagenome and host genome was identified by comparing biological pathway enrichment between the RA metagenome and the RA genome-wide association study results. No apparent discrepancy in alpha or beta diversities of metagenome was found between RA cases and controls. CONCLUSION: Our shotgun sequencing-based MWAS highlights a novel link among the gut microbiome, host genome and pathology of RA, which contributes to our understanding of the microbiome's role in RA aetiology.

Artificial bioinorganic clusters of dinuclear 3d-transition metal ions coordinated by an inorganic coordination ligand.

A new biologically relevant cubane-type artificial inorganic ligand was developed to support 3d-transition metal ions of Mn(II), Co(II), Ni(II), Zn(II), Fe(III), and also In(III). All of the reactions produce dinuclear cationic clusters of [({Co(tacn)}2HMo3O13∙H2O){M(H2O)2}]2n+ (M = Mn2+ (4Mn), Co2+ (4Co), Ni2+ (4Ni), Zn2+ (4Zn), n = 2; M = Fe3+ (5), In3+ (6), n = 4), where tacn is the abbreviation of 1,4,7-triazacyclononane ligand. Clusters 4 do not dissolve in any solvents at all to prevent the recrystallization or the further characterization whereas the high solubility of clusters 5 and 6 allowed us to characterize the solution state properties. The dinuclear cores are separated at a fixed-distance in the range of 5.66-5.77 Šfor M(II) complexes and 5.45-5.65 Šfor M(III) complexes. Each 3d-transition metal ion is supported by two pairs of cis-oxido groups from a cubane unit formed by CoMo3O3(OH) group, and remaining two sites on the 3d-transition metal centers are occupied by two water molecules. The hydroxido group on the cubane unit provides an interaction route through bifurcated hydrogen bondings between dinuclear centers. Three consecutive stepwise reduction waves were observed at -0.73, -0.91, and -1.16 mV vs Fc+/Fc for 5 in cyclic voltammetry and the comparison with the redox inactive In3+ complex revealed that two iron centers are interacted each other through the inorganic ligand which gave a reduction wave observed at -0.91 mv vs Fc+/Fc.

[Clinical features of adult-onset chronic active Epstein-Barr virus infection].

Chronic active Epstein-Barr virus infection (CAEBV) presents with mononucleosis-like symptoms such as chronic persistent or recurrent pyrexia, lymphadenopathy, and hepatosplenomegaly because of the reactivation of Epstein-Barr virus (EBV) as demonstrated by the recurrence of EBV-infected cells. The mechanism of CAEBV remains obscure, and CAEBV can lead to fatal conditions such as hemophagocytic syndrome and malignant lymphoma by clonal expansion of EBV-infected T- or NK-cells. Without hematopoietic stem cell transplantation, CAEBV has a poor prognosis. CAEBV is listed in the revised 2016 World Health Organization classification as a chronic active EBV infection of T- and NK-cell types, systemic form, among EBV-positive T- and NK-cell lymphoproliferative diseases of childhood. However, similar clinical conditions have been reported in adult patients. Therefore, we investigated the clinical features of adult patients with CAEBV-like features (adult-onset CAEBV) in a relatively small number of cases. Additionally, genetic alterations related to CAEBV development have also been reported. Along with these results, we reviewed the clinical characteristics of adult-onset CAEBV.

Transient severe conduction disturbances associated with ankylosing spondylitis.

A 46-year-old man presented with advanced and complete atrioventricular block. He was diagnosed with human leukocyte antigen-B27-positive ankylosing spondylitis (AS) and treated with nonsteroidal anti-inflammatory drugs for AS. The severe atrioventricular block spontaneously improved and resolved after 3 months of therapy. Sequential cardiac magnetic resonance imaging demonstrated transient myocardial high-intensity signals in the basal septum close to the membranous portion of the septum. A pacemaker was not needed because of the reversible atrioventricular block.