Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ATHEROSCLEROSIS SOC  

Aims: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors and an increased risk of cardiovascular events. The carotid intima-media thickness (CIMT) is correlated with coronary and carotid atherosclerosis, and is a significant predictor of cardiovascular events. Tissue factor (TF) is an initiator of the extrinsic coagulation cascade and is expressed on peripheral blood monocytes and macrophages in atherosclerotic plaques. TF plays important roles in both thrombosis and atherosclerosis. No study has investigated the relationship between monocyte TF activity and CIMT in MS patients.
Methods: Peripheral blood mononuclear cells (PBMCs) were collected from 39 normal subjects and 110 patients with MS. The procoagulant activity (PCA) in monocytes was measured using a one-stage clotting assay and is expressed as the mean +/- SD (mU TF/10(6) PBMCs).
Results: The PCA in monocytes in MS patients was significantly higher than in normal subjects (86.2 +/- 69.5 vs. 52.4 +/- 9.9 mU TF/10(6) PBMCs, p < 0.001). In multivariate analysis, patient age (beta coefficient = 0.373, p < 0.001), high-density lipoprotein cholesterol (beta coefficient = -0.307, p = 0.001) and PCA (beta coefficient = 0.422, p = 0.002) were each significantly and independently associated with CIMT.
Conclusions: These data indicate that the upregulation of monocyte TF activity is significantly associated with CIMT in MS patients.

DOI： 10.5551/jat.6874

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

Background: An elevation of the cardiac troponin T (TnT) level identifies patients with ongoing myocardial damage (OMD) and at increased risk for future cardiac events in chronic heart failure (CHF). C-reactive protein (CRP) upregulates monocyte proinflammatory cytokine production and this upregulalion appears to play an important role on OMD.
Methods and Results: Peripheral blood mononuclear cells (PBMCs) were stimulated by 25 mu g/mL CRP in 72 patients with CHF. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production by monocytes was measured by a specific enzyme-linked immunosorbent assay and expressed as the mean +/- SD (pg.mL.10(6) PBMCs). The patients were divided into 2 groups according to the TnT levels: 27 patients with OMD (TnT >= 0.01 ng/mL) and 45 patients without OMD. CRP-induced cytokine production was upregulated significantly more in patients with OMD than in those without OMD (TNF-alpha.: 200.6 +/- 100.4 vs. 102.1 +/- 73.6 pg/mL, P < .001, IL-6: 4611.7 +/- 2600.0 vs. 1451.6 +/- 1193.5 pg/mL, P < .001). Multivariate Cox regression analyses revealed that CRP-stimulated monocyte production of TNF-alpha 120 pg/mL and TnT >= 0.03 ng/mL were independent predictors of cardiac events.
Conclusions: The upregulation of monocyte proinflammatory cytokine production by CRP could be significantly related to OMD and future cardiac events in CHF. (J Cardiac Fail 2010;16:562-571)

DOI： 10.1016/j.cardfail.2010.02.003

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC IMMUNOLOGISTS  

The S100 calcium-binding proteins S100A8 and S100A9 are elevated systemically in patients with viral infections. The S100A8-S100A9 complex facilitated viral replication in human CD4(+) T lymphocytes latently infected with HIV-1- and S100A8-induced HIV-1 transcriptional activity. Mechanisms inducing the S100 genes and the potential source of these proteins following viral activation are unknown. In this study, we show that S100A8 was induced in murine macrophages, and S100A8 and S100A9 in human monocytes and macrophages, by polyinosinic: polycytidylic acid, a dsRNA mimetic. Induction was at the transcriptional level and was IL-10 dependent. Similar to LPS-induced S100A8, induction by dsRNA was dependent on p38 and ERK MAPK. Protein kinase R (PKR) mediates antiviral defense and participates in MyD88-dependent/independent signaling triggered by TLR4 or TLR3. Like IL-10, S100 induction by polyinosinic:polycytidylic acid and by LPS was inhibited by the specific PKR inhibitor 2-aminopurine, indicating a novel IL-10, PKR-dependent pathway. Other mediators such as IFN-beta, which synergized with dsRNA, may also be involved. C/EBP beta bound the defined promoter region in response to dsRNA. S100A8 was expressed in lungs of mice infected with influenza virus and was maximal at day 8 with strong immunoreactivity in epithelial cells lining the airways and in mononuclear cells and declined early in the recovery phase, implying down-regulation by mediator(s) up-regulated during resolution of the infection. IL-10 is implicated in viral persistence. Since S100A8/S100A9 levels are likely to be maintained in conditions where IL-10 is raised, these proteins may contribute to viral persistence in patients infected by some RNA viruses. The Journal of Immunology, 2009, 182: 2258-2268.

DOI： 10.4049/jimmunol.0802683

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

Leukocyte immunoglobulin-like receptor A5 (LILRA5) belongs to a family of receptors known to regulate leukocyte activation, There are two membrane-bound and two soluble forms of LILRA5. The transmembrane LILRA5 contain a short cytoplasmic domain and a charged arginine residue within the transmembrane region. Cross-linking of LILRA5 on monocytes induced production of pro-inflammatory cytokines, suggesting that LILRA5 plays a role in inflammation. However, expression of LILRA5 in diseases with extensive inflammatory component is unknown. Rheumatoid arthritis (RA) is a chronic inflammatory synovitis characterized by unregulated activation of leukocytes leading to joint destruction. Here we demonstrate extensive LILRA5 expression on synovial tissue macrophages and in synovial fluid of patients with active RA but not in patients with osteoarthritis. We also show that LILRA5 associated with the common gamma chain of the FcR and LILRA5 cross-linking induced phosphorylation of Src tyrosine kinases and Spleen tyrosine kinase (Syk). Furthermore, LILRA5 induced selective production of pro-inflammatory cytokines as well as IL-10. LILRA5 mRNA and protein expression was tightly regulated by TNF-alpha, IL-10 and IFN-gamma. Increased expression of LILRA5 in rheumatoid tissue, together with its ability to induce key cytokines involved in RA, suggests that this novel receptor may contribute to disease pathogenesis.

DOI： 10.1002/eji.200838415

Web of Science

researchmap

researchmap

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

Growth factors, including fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (TGF-beta) regulate fibroblast function, differentiation and proliferation. S100A8 and S100A9 are members of the S100 family of Ca2+-binding proteins and are now accepted as markers of inflammation. They are expressed by keratinocytes and inflammatory cells in human/murine wounds and by appropriately activated macrophages, endothelial cells, epithelial cells and keratinocytes in vitro. In this study, regulation and expression of S100A8 and S100A9 were examined in fibroblasts. Endotoxin (LPS), interferon gamma (IFN gamma), tumour-necrosis factor (TNF) and TGF-beta did not induce the S100A8 gene in murine fibroblasts whereas FGF-2 induced mRNA maximally after 12 h. The FGF-2 response was strongly enhanced and prolonged by heparin. Interleukin-1 beta (IL-1 beta) alone, or in synergy with FGF-2/heparin strongly induced the gene in 3T3 fibroblasts. S100A9 mRNA was not induced under any condition. Induction of S100A8 in the absence of S100A9 was confirmed in primary fibroblasts. S100A8 mRNA induction by FGF-2 and IL-1 beta was partially dependent on the mitogen-activated-protein-kinase pathway and dependent on new protein synthesis. FGF-2-responsive elements were distinct from the IL-1 beta-responsive elements in the S100A8 gene promoter. FGF-2-/heparin-induced, but not IL-1 beta-induced responses were significantly suppressed by TGF-beta, possibly mediated by decreased mRNA stability. S100A8 in activated fibroblasts was mainly intracytoplasmic. Rat dermal wounds contained numerous S100A8-positive fibroblast-like cells 2 and 4 days post injury; numbers declined by 7 days. Up-regulation of S100A8 by FGF-2/IL-1 beta, down-regulation by TGF-beta, and its time-dependent expression in wound fibroblasts suggest a role in fibroblast differentiation at sites of inflammation and repair.

DOI： 10.1111/j.1742-4658.2005.04703.x

Web of Science

researchmap

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Background: A wide QRS complex is not a rare electrocardiographic phenomenon at the termination of paroxysmal supraventricular tachycardia (PSVT), but no plausible underlying mechanism has yet been proposed. The purpose of the present study was to elucidate the frequency and the underlying mechanism of the wide QRS complexes at the termination of PSVT. Methods: We retrospectively reviewed 305 electrocardiograms (ECGs) from 100 patients, on which PSVT termination was recorded. The frequency of the wide QRS complexes was analyzed in 181 ECGs to avoid duplication, because there were 124 ECGs obtained from the same patients with same methods. The 181 ECGs were divided by morphology into three groups: Type A, termination with wide QRS complex without pause
Type B, wide QRS complex following initial pause after termination
Type C, wide QRS complex following the first narrow QRS after termination. Results: The wide QRS complex was recorded in 81/181 (44.8%) ECGs (Type A
3/81 (3.7%), Type B
44/81 (54.3%), Type C
62/81 (55.6%)) and its frequency was not dependent on the mechanism of PSVT. It was more frequently observed after a long pause, and was frequently induced by procedures that increase vagal tone, such as intravenous adenosine 5′-triphosphate administration (16/22:72.7%) and vagal stimulation maneuvers (16/32:50%). There were a total of 41 wide QRS complexes (44.6%) which had a preceding sinus P wave, out of a total of 92 wide QRS complexes in all three types. These 41 wide QRS complexes included 30/44 (68.2%) Type B wide QRS, and 11 (24.4%) Type C wide QRS complexes. Conclusion. The aberrant conduction or escaped ventricular contraction was suggested to be the underlying mechanism of the majority of wide QRS complexes and ventricular premature contraction is less frequent.

DOI： 10.1272/jnms.69.525

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY, INC  

Objectives: To elucidate pharmacokinetics and pharmacodynamics of landiolol hydrochloride, newer developed ultra-short-acting beta-blocker, in patients with various cardiac tachyarrhythmias.
Background: The short duration of action and titratability of landiolol hydrochloride make it ideal for use in patients with a clinical need for beta-blockers.
Methods: In a total of 31 examinations we infused the drug in 19 patients (mean age, 55 +/- 14 years). After the persistence of the tachyarrhythmias was confirmed, continuous infusion was started at rates of 0.005, 0.01, 0.02, 0.04, and 0.08 mg/kg/min for 5 minutes (for paroxysmal atrial fibrillation, paroxysmal supraventricular tachycardia, and ventricular tachycardia) or 15 minutes (for ventricular premature complex). We analyzed the pharmacokinetics of 16 examinations. A one-compartment model provided a close fit for each blood concentration-time curve.
Results: The maximum blood concentrations obtained clearly showed the dose dependency and revealed very short half-lives (range, 2.3 to 4.0 minutes). Area under the blood concentration-time curves also increased, showing dose dependency. In paroxysmal atrial fibrillation, landiolol hydrochloride reduced the heart rate from 111 +/- 20 to 90 +/- 10/min. Sinus rhythm was restored, without any adverse effects, in three of five patients with paroxysmal supraventricular tachycardia and one patient with ventricular tachycardia, There was no significant change in peripheral blood pressure,
Conclusions: Landiolol hydrochloride has a shorter elimination half-life than any other beta-blocker, and it can be administered safely to patients with various tachyarrhythmias.

DOI： 10.1067/mcp.2000.108733

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Whether phosphodiesterase inhibitors increase the heart rate in patients with bradyarrhythmias is not known. We attempted to determine whether the oral phosphodiesterase inhibitor cilostazol exhibits beneficial chronotropic effects in patients with symptomatic bradyarrhythmias. Twenty patients comprising eight with bradycardic atrial fibrillation, eight with sick sinus syndrome, and four with Wenckebach-type atrioventricular block, whose 24-h total heart-beat count was less than or equal to 70,000 brats and whose maximal RR interval was greater than or equal to 2.5 s, were enrolled. Holter recordings (24-h) were made before and 2 weeks after oral daily administration of 200 mg of cilostazol. Cilostazol increased the 24-h total heart-beat count from 77,429 +/- 11,168 to 107,981 +/- 13,536 (95% confidence interval, 24,605-36,397; p < 0.0001), the minimal heart rate from 33 +/- 9 47 +/- 13 beats/min (95% confidence interval, 9-19 beats/min; p < 0.0001), and the maximal RR interval from 3,149 +/- 1,018 to 2,087 +/- 601 ms (95% confidence interval, -1,517 to -608 ms; p = 0.0001). Only two patients had headaches as adverse effects. In conclusion, cilostazol had a beneficial positive chronotropic effect in patients with bradyarrhythmias, especially with bradycardic atrial fibrillation and sick sinus syndrome.

DOI： 10.1097/00005344-199804000-00010

Web of Science

researchmap

DOI： 10.1272/jnms1923.64.546

researchmap