Expression of prostacyclin-stimulating factor (PSF) in mononuclear cells of human peripheral blood and THP-1 derived macrophage-like cells, and effects of high glucose concentration

Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to development of diabetic angiopathies including that in atherosclerosis. We identified a bioactive peptide, prostacyclin-stimulating factor (PSF), which stimulates PGI2 synthesis in cultured aortic ECs. Our previous studies demonstrated that PSF was predominantly expressed by arterial smooth muscle cells (SMCs) and ECs. We immunohistochemically showed that PSF existed in SMCs of human coronary arteries, and PSF staining was markedly reduced in coronary arterial SMCs of patients with type 2 diabetes and/or myocardial infarction. In the present study, we investigated the existence of PSF in human serum, and effects of glucose on serum PSF levels in patients with type 2 diabetes. Immunoblot analysis revealed the presence of PSF in serum, and showed that serum PSF protein concentration was significantly decreased in type 2 diabetic patients. Moreover, there was a significant negative correlation between serum PSF and HbA1c levels in these patients. Using immunohistochemistry, we also showed that PSF was present in serum and in macrophages (Mfs). PSF mRNA was found in Mfs using reverse transcription-polymerase chain reaction (RT-PCR). In addition, effects of high glucose conditions on PSF production in Mfs were examined by Western blotting, and we showed that PSF significantly decreased when Mfs were cultured in high glucose conditions. These results strongly suggested that decreased PSF production might result in decreased production of PGI_2 in atherosclerotic lesions, thus leading to development of diabetic macroangiopathy and atherosclerosis

CORONARY ARTERY MORPHPLOGY AND REACTIVITY TO ACUTE HYPOXIA IN CHRONIC PULMONARY DISEASE

In patients with chronic pulmonary disase (CPD), myocardial infarction is rare. To elucidate why this is so, we investigated the morphological changes and the reactivity of the coronary artery to acute hypoxia in patients with CPD. Sixty patients with CPD and 28 normal subjects were studied. Measurements of pulmonary homodynamics and coronary angiography were undertaken before and after inhalation of 13%O2 for 15 minutes. The size of the coronary arteries was measured using a densitometric method, and a coronary narrowing score was calculated according to the WHO criteria. The size of the left anterior descending artery of patients with low %VC and hypoxia was larger than that of the normal subjects. In patients with CPD, the coronary narrowing score was low and the atherosclerotic change was minimal. The reactivity of the coronary arteries to acute hypoxia was reduced in patients with CPD when compared with normal subjects

小児急性リンパ性白血病のL-アスパラギナーゼを含む寛解導入療法ではトロンピン・プラスミン生成試験において著明な線溶抑制を主体とする凝固障害を示す。

Background: L-asparaginase (L-Asp)-associated thromboembolisms are serious complications in pediatrics patients with acute lymphoblastic leukemia (ALL), especially at ≥10.0 years old, but the pathogenesis remains to be clarified. Procedure: We conducted a multicenter, prospective study of 72 patients with ALL aged 1.0 to 15.2 years treated with either a Berlin-Frankfurt-Münster (BFM) 95-ALL oriented regimen or Japan Association of Childhood Leukemia Study ALL-02 protocol. We divided patients into each treatment protocol and investigated the dynamic changes in coagulation and fibrinolysis using simultaneous thrombin and plasmin generation assay. Patients' plasma samples were collected at the prephase (T0), intermittent phase (T1), and postphase of L-Asp therapy (T2), and postinduction phase (T3). Measurements of endogenous thrombin potential (T-EP) and plasmin peak height (P-Peak) were compared to normal plasma. Results: None of the cases developed thromboembolisms. Median ratios of T-EP and P-Peak for the controls in the JACLS group were 1.06 and 0.87 (T0), 1.04 and 0.71 (T1), 1.02 and 0.69 (T2), and 1.20 and 0.92 (T3), respectively, while those in the BFM group were 1.06 and 1.00 (T0), 1.04 and 0.64 (T1), 1.16 and 0.58 (T2), and 1.16 and 0.85 (T3), respectively. In particular, P-Peak ratios were depressed at T1 and T2 compared to T0 in the BFM group (P < .01). Moreover, P-Peak ratios in patients ≥10.0 years old were lower at T1 in the BFM group (P = .02). Conclusions: The results demonstrated that hemostatic dynamics appeared to shift to a hypercoagulable state with marked hypofibrinolysis associated with L-Asp therapy, especially in patients ≥10.0 years old following the BFM regimen.博士（医学）・甲第722号・令和元年12月5日© 2019 Wiley Periodicals, Inc.This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1002/pbc.28016], which has been published in final form at [https://doi.org/10.1002/pbc.28016]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Comparison with Magnetic Resonance Three-Dimensional Sequence for Lumbar Nerve Root with Intervertebral Foramen

Study DesignProspective study based on magnetic resonance (MR) imaging of the lumbar spinal root of the intervertebral foramen.PurposeThis study was to compare MR three-dimensional (3D) sequences for the evaluation of the lumbar spinal root of the intervertebral foramen.Overview of LiteratureThe diagnosis of spinal disorders by MR imaging is commonly performed using two-dimensional T1- and T2-weighted images, whereas 3D MR images can be used for acquiring further detailed data using thin slices with multi-planar reconstruction.MethodsOn twenty healthy volunteers, we investigated the contrast-to-noise ratio (CNR) of the lumbar spinal root of the intervertebral foramen with a 3D balanced sequence. The sequences used were the fast imaging employing steady state acquisition and the coherent oscillatory state acquisition for the manipulation of image contrast (COSMIC). COSMIC can be used with or without fat suppression (FS). We compared these sequence to determine the optimized visualization sequence for the lumbar spinal root of the intervertebral foramen.ResultsFor the CNR between the nerve root and the peripheral tissue, these were no significant differences between the sequences at the entry of foramen. There was a significant difference and the highest CNR was seen with COSMIC-FS for the intra- and extra-foramen.ConclusionsIn this study, the findings suggest that the COSMIC-FS sequences should be used for the internal or external foramen for spinal root disorders

Complications of Evans' syndrome in an infant with hereditary spherocytosis: a case report

Hereditary spherocytosis (HS) is a genetic disorder of the red blood cell membrane clinically characterized by anemia, jaundice and splenomegaly. Evans' syndrome is a clinical syndrome characterized by autoimmune hemolytic anemia (AIHA) accompanied by immune thrombocytopenic purpura (ITP). It results from a malfunction of the immune system that produces multiple autoantibodies targeting at least red blood cells and platelets. HS and Evans' syndrome have different mechanisms of pathophysiology one another. We reported the quite rare case of an infant who had these diseases concurrently. Possible explanations of the unexpected complication are discussed

Risk-adjusted therapy for pediatric non-T cell ALL improves outcomes for standard risk patients: results of JACLS ALL-02

This study was a second multicenter trial on childhood ALL by the Japan Childhood Leukemia Study Group (JACLS) to improve outcomes in non-T ALL. Between April 2002 and March 2008, 1138 children with non-T ALL were enrolled in the JACLS ALL-02 trial. Patients were stratified into three groups using age, white blood cell count, unfavorable genetic abnormalities, and treatment response: standard risk (SR), high risk (HR), and extremely high risk (ER). Prophylactic cranial radiation therapy (PCRT) was abolished except for CNS leukemia. Four-year event-free survival (4yr-EFS) and 4-year overall survival (4yr-OS) rates for all patients were 85.4% ± 1.1% and 91.2% ± 0.9%, respectively. Risk-adjusted therapy resulted in 4yr-EFS rates of 90.4% ± 1.4% for SR, 84.9% ± 1.6% for HR, and 66.5% ± 4.0% for ER. Based on NCI risk classification, 4yr-EFS rates were 88.2% in NCI-SR and 76.4% in NCI-HR patients, respectively. Compared to previous trial ALL-97, 4yr-EFS of NCI-SR patients was significantly improved (88.2% vs 81.2%, log rank p = 0.0004). The 4-year cumulative incidence of isolated (0.9%) and total (1.5%) CNS relapse were significantly lower than those reported previously. In conclusion, improved EFS in NCI-SR patients and abolish of PCRT was achieved in ALL-02

Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency

X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency characterized by increased vulnerability to Epstein-Barr virus infection. XLP type 1 is caused by mutations in SH2D1A, whereas X-linked inhibitor of apoptosis (XIAP) encoded by XIAP/BIRC4 is mutated in XLP type 2. In XIAP deficiency, hemophagocytic lymphohistiocytosis (HLH) occurs more frequently and recurrence is common. However, the underlying mechanisms remain mostly unknown. We describe the characteristics of the cytokine profiles of serum samples from 10 XIAP-deficient patients. The concentration of interleukin (IL)-18 was strikingly elevated in the patients presented with HLH, and remained high after the recovery from HLH although levels of other pro-inflammatory cytokines approached the normal range. Longitudinal examination of two patients demonstrated marked exacerbation of IL-18 levels during every occasion of HLH. These findings may suggest the association between HLH susceptibility and high serum IL-18 levels in XIAP deficiency. © 2013 Elsevier Ltd. All rights reserved

Surgical benefits of liver hanging maneuver for hepatectomy of huge liver tumor

In hepatic surgery, it is very important to control bleeding during liver resection. However, in hepatectomy for a huge liver tumor it is often difficult to reduce bleeding volume and maintain an excellent surgical view. The anterior pproach, which is hepatectomy done using the liver hanging maneuver, has beneficial effects reducing bleeding volume and preventing scattering of cancer cells from huge liver tumors. W e investigated the surgical benefits of the liver anging maneuver during hepatectomy for huge liver tumors in our department.