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Background:A relationship has been reported between blood concentrations of coagulation factor VII (FVII) and obesity. In addition to its role in coagulation, FVII has been shown to inhibit insulin signals in adipocytes. However, the production of FVII by adipocytes remains unclear.Objective:We herein investigated the production and secretion of FVII by adipocytes, especially in relation to obesity-related conditions including adipose inflammation and sympathetic nerve activation.Methods:C57Bl/6J mice were fed a low- or high-fat diet and the expression of FVII messenger RNA (mRNA) was then examined in adipose tissue. 3T3-L1 cells were used as an adipocyte model for in vitro experiments in which these cells were treated with tumor necrosis factor-α (TNF-α) or isoproterenol. The expression and secretion of FVII were assessed by quantitative real-time PCR, Western blotting and enzyme-linked immunosorbent assays.Results:The expression of FVII mRNA in the adipose tissue of mice fed with high-fat diet was significantly higher than that in mice fed with low-fat diet. Expression of the FVII gene and protein was induced during adipogenesis and maintained in mature adipocytes. The expression and secretion of FVII mRNA were increased in the culture medium of 3T3-L1 adipocytes treated with TNF-α, and these effects were blocked when these cells were exposed to inhibitors of mitogen-activated kinases or NF-κB activation. The β-adrenoceptor agonist isoproterenol stimulated the secretion of FVII from mature adipocytes via the cyclic AMP/protein kinase A pathway. Blockade of secreted FVII with the anti-FVII antibody did not affect the phosphorylation of Akt in the isoproterenol-stimulated adipocytes.Conclusion:Obese adipose tissue produced FVII. The production and secretion of FVII by adipocytes was enhanced by TNF-α or isoproterenol via different mechanisms. These results indicate that FVII is an adipokine that plays an important role in the pathogenesis of obesity. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibodies (aPL) are associated with an increased risk of thrombosis; however, the mechanism remains unknown. Recent studies have focused on the impediment of protein C anticoagulant activity by anti-β2-glycoprotein I (β2GPI) antibodies (aβ2GPI Ab). We purified IgG fractions containing a high concentration of aβ2GPI Ab from patients with antiphospholipid syndrome (APS) and then investigated the effect of purified aβ2GPI Ab on the activity of activated protein C (APC). Using a three-step chromatography method (DEAE-sepharose column, phosphatidylserine polyacrylamide gel column dependent on the presence of β2GPI, and protein G column chromatography), we successfully isolated anti-β2GPI IgG from nine patients with APS. Seven of nine samples inhibited APC activity in a concentration-dependent manner only in the presence of β2GPI, as observed by a chromogenic assay that was able to determine thrombin activity even in the presence of APC. The extent of APC inhibition by these fractions appeared to be related to aβ2GPI Ab titers of the purified IgG. However, the inhibitory effect of IgG from patients was not detected in the absence of β2GPI. IgG purified from three normal subjects did not affect APC activity. Herein, we show a useful method for the isolation of IgG containing a high concentration of aβ2GPI Ab. Moreover, the present findings indicate that inhibition by aβ2GPI Ab on APC anticoagulant activity could explain one of the mechanisms for the thrombotic state in APS. [ABSTRACT FROM AUTHOR]

Background To establish an available, economical technique for the large-scale purification of CD34 + cells we used a nylon-fiber syringe (NF-S) for depletion of adherent cells and then selected CD 34 + cells from peripheral blood mobilized by G-CSF, using MAb and magnetic heads. Methods PBSC were mobilized and collected from adult, healthy volunteers. With the effect of concentration of anti-CD34 MAb (9C5) on the purification of CD34 + cells from 1 × 10 8 NF-S treated cells (NF cells), the recovery and the purity of CD34 + cells was identical for 5, 10, 20, 40 µg of 9C5. In this study, therefore, the concentration of 9C5 was maintained at >5 µg/10 8 NF cells, with a cellhead ratio of 1:10. Results When half to one-third of leukapheresis product containing 121.5 ± 26.0 × 10 8 mononuclear cells (mean ± SD; n = 6) was processed for CD34 + cell purification, 5.26 ± 3.01 × 10 7 total purified cells were obtained with a purity of CD34 + cells at 94.9 ± 8.5%. The numbers of CD34 + cells and total progenitor cells recovered in this process were 4.71 ± 2.33 × 10 7 cells and 145.9 + 121.8 × 10 5 cells, respectively. The total recovery of CD34 + cells was 37.0 ± 21.0%. The depletion of monocyte by NF-S reduced the 9C5 anti-human CD34 MAb needed for purification of CD34 + cells to one-third. Two patients were grafted with peripheral blood CD34 + cells selected by this procedure and achieved a rapid and consistent hematopoiesis. Discussion Our clinical data show that these cells are capable of rapid reconstitution of hematopoiesis after high-dose chemotherapy. The procedure contains an additional step; however, consistent high purity of CD34 + cells in the purified population and cost reduction were achieved, both critical issues in the better purging of malignant cells and for a wide clinical application. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case study of a 73-year-old Japanese woman who has livedoid vasculopathy (LV) and the severe pain was treated with apixaban drug.

The article presents the case history of a patient with Trousseau's syndrome. The case associates the tissue factor coming from lung cancer as the cause of recurrent deep vein thrombosis (DVT) and pulmonary thromboembolism (PE). In April 2002, a man was diagnosed with DVT and PE after the symptoms of dry cough and dull pain in his right leg. The patient has the history of cigarette smoking and inhalation of toxic substances.

Comments on a study on whether multiple thrombosis in major arteries in a patient with antiphospholipid syndrome (APS) is associated with excess of a large multimer of von Willebrand factor. Results of laboratory investigations of antiphospholipid antibodies; Details on the study; Characteristics of catastrophic APS.