Large eddy simulation of LDL surface concentration in a subject specific human aorta

The development of atherosclerosis is correlated to the accumulation of lipids in the arterial wall, which, in turn, may be caused by the build-up of low-density lipoproteins (LDL) on the arterial surface. The goal of this study was to model blood flow within a subject specific human aorta, and to study how the LDL surface concentration changed during a cardiac cycle. With measured velocity profiles as boundary conditions, a scale-resolving technique (large eddy simulation, LES) was used to compute the pulsatile blood flow that was in the transitional regime. The relationship between wall shear stress (WSS) and LDL surface concentration was investigated, and it was found that the accumulation of LDL correlated well with WSS. In general, regions of low WSS corresponded to regions of increased LDL concentration and vice versa. The instantaneous LDL values changed significantly during a cardiac cycle; during systole the surface concentration was low due to increased convective fluid transport, while in diastole there was an increased accumulation of LDL on the surface. Therefore, the near-wall velocity was investigated at four representative locations, and it was concluded that in regions with disturbed flow the LDL concentration had significant temporal changes, indicating that LDL accumulation is sensitive to not only the WSS but also near-wall flow.     

Molecular heterogeneity of angiotensin converting enzyme in human cerebrospinal fluid.

Three different molecular forms of angiotensin converting enzyme (ACE) (approximately Mr 150,000, 80,000 and 40,000, respectively), have been recovered from human cerebrospinal fluid. All three enzymes were inhibited by captopril and enalapril and their activity was potentiated by chloride ions. They were capable of degrading Leu-enkephalin-Arg6 and substance -P, but gave no conversion of neurokinin A. In all these aspects, the CSF enzymes were identical with the human pulmonary enzyme. The Mr 40,000 form of ACE is the smallest active form of the enzyme hitherto reported and is likely to represent a fragment of the C-terminal part of native ACE, where its active center is located.     

Adhesion molecules in subjects with COPD and healthy non-smokers: a cross sectional parallel group study

Background

The aim of the study was to investigate how the expression of adhesion molecules changes as neutrophils migrate from the circulation to the lung and if these changes differ between non-smoking subjects and smokers with and without COPD.

Methods

Non-smoking healthy subjects (n=22), smokers without (n=21) and with COPD (n=18) were included. Neutrophils from peripheral blood, sputum and bronchial biopsies were analysed for cell surface expression of adhesion molecules (CD11b, CD62L, CD162). Serum, sputum supernatant and BAL-fluid were analysed for soluble adhesion molecules (ICAM-1, -3, E-selectin, P-selectin, VCAM-1, PECAM-1).

Results

Expression of CD11b was increased on circulating neutrophils from smokers with COPD. It was also increased on sputum neutrophils in both smokers groups, but not in non-smokers, as compared to circulating neutrophils.Serum ICAM-1 was higher in the COPD group compared to the other two groups (p<0.05) and PECAM-1 was lower in smokers without COPD than in non-smoking controls and the COPD group (p<0.05). In BAL-fluid ICAM-1 was lower in the COPD group than in the other groups (p<0.05).

Conclusions

Thus, our data strongly support the involvement of a systemic component in COPD and demonstrate that in smokers neutrophils are activated to a greater extent at the point of transition from the circulation into the lungs than in non-smokers.     

Dendritic cell maturation controls adhesion, synapse formation, and the duration of the interactions with naive T lymphocytes

The initiation of adaptive immune responses requires the direct interaction of dendritic cells (DCs) with naive T lymphocytes. It is well established that the maturation state of DCs has a critical impact on the outcome of the response. We show here that mature DCs form stable conjugates with naive T cells and induce the formation of organized immune synapses. Immature DCs, in contrast, form few stable conjugates with no organized immune synapses. A dynamic analysis revealed that mature DCs can form long-lasting interactions with naive T cells, even in the absence of Ag. Immature DCs, in contrast, established only short intermittent contacts, suggesting that the premature termination of the interaction prevents the formation of organized immune synapses and full T cell activation.     

High enkephalyl peptide degradation, due to angiotensin-converting enzyme-like activity in human CSF

The metabolism of enkephalin peptides was studied in human cerebrospinal fluid. The degradation rates of (Leu)-enkephalin and (Leu)-enkephalin-Arg6 were compared and the latter was degraded at a 10-fold higher rate. The major enzyme activity was investigated by Mr determination and inhibition experiments, showing marked similarity with angiotensin-converting enzyme.     

The human cornea has a high incidence of acquired chromosome abnormalities

Structurally and functionally, the human cornea is a highly specialized tissue. The corneal stromal collagen matrix is uniquely transparent and yet maintains a mechanically tough and chemically impermeable barrier between the eye and environment. We report for the first time that stromal keratocytes of the human cornea show cytogenetic abnormalities with a frequency that is unprecedented among normal tissues. The abnormalities are acquired, clonal and nonclonal, primarily aneuploid in nature, and present in normal as well as diseased corneas. Received: 10 February 1997 / Accepted: 21 May 1997     

Geographical differences in erythemally-weighted UV measured at mid-latitude USDA sites.

UV measurements from instruments maintained by USDA at 16 mid-latitude sites were analysed to investigate geographic differences. Fifteen of the sites are in North America, and one is in New Zealand. The instruments measure erythemally weighted UV radiation, and the results are presented in terms of UV Index (UVI). The focus of this work is on data from 2003, but the main results are also shown for years 2002 and 2004. In the North American sites, the peak UVI values increase by approximately 15% between latitudes 47 degrees N and 40 degrees N, and they show an increase with altitude of approximately 15% in the first kilometer, but much smaller rates of increase above that level. Peak UV intensities in the New Zealand site (45 degrees S, alt. 0.37 km) exceed those at comparable latitudes and altitudes in North America by 41 +/- 5%, and are more comparable with those over 1 km higher and 5 degrees closer to the equator. The number of observations on these days that exceeded various thresholds of UVI showed similar patterns. Furthermore, the number of days in which the peak values exceeded various thresholds also showed similar patterns, with the number of extreme values in New Zealand being anomalously high. For example, the only sites in North America where UVI exceeded 12 were at the high altitude sites in Colorado and Utah, for which there were 53 days, 6 days and 2 days respectively at the 3.2 km, 1.6 and 1.4 km sites. By contrast, the peak UVI at Lauder (0.37 km) exceeded 12 on 17 days. Lauder was the only site under 1 km altitude where the UVI exceeded 11 on a regular basis (48 days). The optical depths at Lauder were significantly lower than at all North American sites. These, together with the lower ozone amounts and the closer Earth-Sun separation in summer all contribute to the relatively high UV intensities at the New Zealand site. Other sites in New Zealand show similar increases compared with corresponding sites in North America, and the differences persist from year to year. The contrast in UV between New Zealand and North America is similar to that observed previously between New Zealand and Europe. During winter months, the UVI in New Zealand is not particularly high, giving a larger summer/winter contrast in UVI, which may be important from a health perspective.