Five steps in leukocyte extravasation in the microcirculation by chemoattractants

For in vivo study of the phenomena observed in vitro, PMN (polymorphonuclear leukocyte) extravasation was analysed quantitatively in the microcirculation of the hamster cheek pouch using a video system. Topical application of leukotriene B4 or N-formyl-methionylleucyl- phenylalanine increased dose dependently the number of PMNs adhering to the venules. Eighty to 90% of the adhering PMNs disappeared from the vascular lumen into the venular wall within 10-12 rain after the adhesion. After PMNs had passed through the endothelial cell layer, they remained in the venular wall for more than 30 min after application of the chemoattractants and appeared in the extravascular space. Thus, the process could be divided into five steps: (1) rolling and (2) adhesion to the endothelium, (3) passage through the endothelial layer (4) remaining in the venular wall, and (5) passage through the basement membrane

Expression and Trafficking of the γ Subunit of Na,K-ATPase in Hypertonically Challenged IMCD3 Cells

The γ subunit (FXYD2) of Na,K-ATPase is an important regulator of the sodium pump. In this investigation we have analysed the trafficking of γ to the plasma membrane in cultures of inner medullary collecting duct cells (IMCD3) following acute hypertonic challenge and brefeldin A (BFA) treatment. Following hypertonic challenging for 24 hr immunofluorescence labeling revealed initial co-localization of the γ subunit and 58K Golgi protein in the cytoplasm, but no co-localization of α1 and Golgi protein. Exposure of the challenged cells to BFA prevented the subsequent incorporation of γ into the basolateral plasma membrane. The γ subunit instead remained in cytoplasmic vesicles while cell proliferation and cell viability decreased simultaneously. Following removal of BFA from the hypertonic medium the IMCD3 cells recovered with distinct expression of γ in the basolateral membrane. The α1 subunit was only marginally influenced by BFA. The results demonstrate that the γ subunit trafficks to the plasma membrane via the Golgi apparatus, despite the absence of a signal sequence. The results also suggest that the γ and α subunits do not traffic together to the plasma membrane, and that the γ and α subunit have different turnover rates during these experimental conditions

Associations of Renal Vascular Resistance With Albuminuria and Other Macroangiopathy in Type 2 Diabetic Patients

OBJECTIVE—Albuminuria can be caused by endothelial dysfunction as a result of ischemic nephropathy rather than classic diabetic nephropathy. We studied whether renal vascular resistance (resistive index [RI]) of the main renal arteries could be associated with albuminuria and further assessed the relationship between RI and aorta stiffness measured by brachial-ankle pulse-wave velocity (baPWV)

Sprint interval and sprint continuous training increases circulating CD34+ cells and cardio-respiratory fitness in young healthy women

The improvement of vascular health in the exercising limb can be attained by sprint interval training (SIT). However, the effects on systemic vascular function and on circulating angiogenic cells (CACs) which may contribute to endothelial repair have not been investigated. Additionally, a comparison between SIT and sprint continuous training (SCT) which is less time committing has not been made

Periodontal disease and atherosclerosis from the viewpoint of the relationship between community periodontal index of treatment needs and brachial-ankle pulse wave velocity

BACKGROUND: It has been suggested that periodontal disease may be an independent risk factor for the development of atherosclerosis. However, the relationship between periodontal disease and atherosclerosis has not been fully elucidated. This study aimed to assess the effects of periodontal disease on atherosclerosis. METHODS: The study design was a cross-sectional study. Subjects were 291 healthy male workers in Japan. We used the Community Periodontal Index of Treatment Needs (CPITN) score, average probing depth and gingival bleeding index (rate of bleeding gums) to assess the severity of periodontal disease. We also used the Brachial-Ankle Pulse Wave Velocity (baPWV) as the index for the development of atherosclerosis. RESULTS: The unadjusted odds ratio (OR) of atherosclerosis in relation to the CPITN score was 1.41 [95% CI: 1.16–1.73]. However, after adjustment for age, systolic blood pressure and smoking, the CPITN score had no relationship with atherosclerosis (adjusted OR: 0.91 [0.68–1.20]). CONCLUSION: Our results show no relationship between mild periodontal disease and atherosclerosis after appropriate adjustments

Metabolic syndrome is associated with change in subclinical arterial stiffness - A community-based Taichung Community Health Study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate the effect of MetS on arterial stiffness in a longitudinal study.</p> <p>Methods</p> <p>Brachial-ankle pulse wave velocity (baPWV), a measurement interpreted as arterial stiffness, was measured in 1518 community-dwelling persons at baseline and re-examined within a mean follow-up period of 3 years. Multivariate linear regression with generalized estimating equations (GEE) were used to examine the longitudinal relationship between MetS and its individual components and baPWV, while multivariate logistic regression with GEE was used to examine the longitudinal relationship between MetS and its individual components and the high risk group with arterial stiffness.</p> <p>Results</p> <p>Subjects with MetS showed significantly greater baPWV at the end point than those without MetS, after adjusting for age, gender, education, hypertension medication and mean arterial pressure (MAP). MetS was associated with the top quartile of baPWV (the high-risk group of arterial stiffness, adjusted odds ratio [95% confidence interval] 1.52 [1.21-1.90]), and a significant linear trend of risk for the number of components of MetS was found (p for trend < 0.05). In further considering the individual MetS component, elevated blood pressure and fasting glucose significantly predicted a high risk of arterial stiffness (adjusted OR [95% CI] 3.72 [2.81-4.93] and 1.35 [1.08-1.68], respectively).</p> <p>Conclusions</p> <p>MetS affects the subject's progression to arterial stiffness. Arterial stiffness increased as the number of MetS components increased. Management of MetS is important for preventing the progression to advanced arterial stiffness.</p

Impact of mediastinal, liver and lung 123I-metaiodobenzylguanidine (123I-MIBG) washout on calculated 123I-MIBG myocardial washout

PURPOSE: In planar (123)I-metaiodobenzylguanidine ((123)I-MIBG) myocardial imaging mediastinum (M) activity is often used as a background correction in calculating "washout" (WO). However, the most likely sources for counts that might produce errors in estimating myocardial (Myo) activity are lung (Lu) and liver (Li), which typically have higher counts/pixel (cpp) than M. The present study investigated the relationship between changes in Lu, Li and Myo activity between early and late planar (123)I-MIBG images, with comparison to M as the best estimator of non-specific background activity. METHODS: Studies on 98 subjects with both early (e) and late (l) planar (123)I-MIBG images were analysed. There were 68 subjects with chronic heart failure (CHF), 14 with hypertension (HTN) but no known heart disease and 16 controls (C). For each image, regions of interest (ROIs) were drawn: an irregular whole Myo, Lu, upper M and Li. For each ROI, WO was calculated as [(cpp(e)-cpp(l:decay corrected))/cpp(e)]x100%. RESULTS: Multivariable forward stepwise regression analysis showed that overall a significant proportion of the variation in Myo WO could be explained by a model containing M WO and Lu WO (37%, p < 0.001). Only in controls was M WO the sole variable explaining a significant proportion of the variation in Myo WO (27%, p = 0.023). CONCLUSION: Although increased Myo WO in CHF subjects reflects disease severity, part of the count differences measured on planar (123)I-MIBG myocardial images likely reflects changes in the adjacent and surrounding Lu tissue. The results for the controls suggest that this is the only group where a mediastinum correction alone may be appropriate for cardiac WO calculation

MFG-E8 Regulates the Immunogenic Potential of Dendritic Cells Primed with Necrotic Cell-Mediated Inflammatory Signals

Dendritic cells (DC) manipulate tissue homeostasis by recognizing dying cells and controlling immune functions. However, the precise mechanisms by which DC recognize different types of dying cells and devise distinct immunologic consequences remain largely obscure. Herein, we demonstrate that Milk-fat globule-EGF VIII (MFG-E8) is a critical mediator controlling DC immunogenicity in inflammatory microenvironments. MFG-E8 restrains DC-mediated uptake and recognition of necrotic cells. The MFG-E8-mediated suppression of necrotic cell uptake by DC resulted in the decreased proinflammatory cytokines production and activated signal components such as STAT3 and A20, which are critical to maintain tolerogenic properties of DC. Furthermore, the DC-derived MFG-E8 negatively regulates the cross-priming and effector functions of antigen-specific T cells upon recognition of necrotic cells. MFG-E8 deficiency enhances an ability of necrotic cell-primed DC to stimulate antitumor immune responses against established tumors. Our findings define what we believe to a novel mechanism whereby MFG-E8 regulates the immunogenicity of DC by modulating the modes of recognition of dying cells. Manipulating MFG-E8 levels in DC may serve as a useful strategy for controlling inflammatory microenvironments caused by various pathological conditions including cancer and autoimmunity