Epigenetics and atherosclerosis

The contribution of epigenetic mechanisms to cardiovascular diseases remains poorly understood. Hypomethylation of genomic DNA is present in human atherosclerotic lesions and methylation changes also occur at the promoter level of several genes involved in the pathogenesis of atherosclerosis, such as extracellular superoxide dismutase, estrogen receptor-α, endothelial nitric oxide synthase and 15-lipoxygenase. So far, no clear data is available about histone modification marks in atherosclerotic lesions. It remains unclear whether epigenetic changes are causally related to the pathogenetic features, such as clonal proliferation of lesion smooth muscle cells, lipid accumulation and modulation of immune responses in the lesions, or whether they merely represent a consequence of the ongoing pathological process. However, epigenetic changes could at least partly explain poorly understood environmental and dietary effects on atherogenesis and the rapid increases and decreases in the incidence of coronary heart disease observed in various populations. RNAi mechanisms may also contribute to the epigenetic regulation of vascular cells. Therapies directed towards modification of the epigenetic status of vascular cells might provide new tools to control atherosclerosis-related cardiovascular diseases.     

Midkine Is Expressed and Differentially Processed during Chronic Obstructive Pulmonary Disease Exacerbations and Ventilator-Associated Pneumonia Associated with Staphylococcus aureus Infection

Staphylococcus aureus is sometimes isolated from the airways during acute exacerbations of chronic obstructive pulmonary disease (COPD) but more commonly recognized as a cause of ventilator-associated pneumonia (VAP). Antimicrobial proteins, among them midkine (MK), are an important part of innate immunity in the airways. In this study, the levels and possible processing of MK in relation to S. aureus infection of the airways were investigated, comparing COPD and VAP, thus comparing a state of disease with preceding chronic inflammation and remodeling (COPD) with acute inflammation (that is, VAP). MK was detected in the small airways and alveoli of COPD lung tissue but less so in normal lung tissue. MK at below micromolar concentrations killed S. aureus in vitro. Proteolytic processing of MK by the staphylococcal metalloprotease aureolysin (AL), but not cysteine protease staphopain A (SA), resulted in impaired bactericidal activity. Degradation was seen foremost in the COOH-terminal portion of the molecule that harbors high bactericidal activity. In addition, MK was detected in sputum from patients suffering from VAP caused by S. aureus but less so in sputum from COPD exacerbations associated with the same bacterium. Recombinant MK was degraded more rapidly in sputum from the COPD patients than from the VAP patients and a greater proteolytic activity in COPD sputum was confirmed by zymography. Taken together, proteases of both bacteria and the host contribute to degradation of the antibacterial protein MK, resulting in an impaired defense of the airways, in particular, in COPD where the state of chronic inflammation could be of importance.     

Effect of habitat, date of laying and density on clutch size of the Great Tit Parus major in northern Finland

The sizes of 1034 Great Tit clutches were studied at the Oulu area (c. 65°N, 25°30'E) in northern Finland. The average size was 9.86 eggs in the first clutch and 7.51 in the second in 13 study areas. The decrease in clutch size from the first to the second laying was most pronounced in those females laying the largest first clutches.
Irrespective of habitat, the clutch size was larger in the sparsely populated areas than in the densest area (Taskila). The clutch size decreased according to the season in all the areas, but this was not as pronounced in Taskila as in the other areas.
The annual average size of the first clutches was inversely related to the breeding density and pronouncedly so to the mean dale of laying. The latter was suggested to be an adaptation to the short season in the northern areas.
An analysis of data from 27 study areas in Europe, north of the Mediterranean region, suggests that the clutch size does not vary with latitude or longitude.     

Genetic diversity and population structure in the outcrossing populations of Equisetum arvense and E. hyemale (Equisetaceae)

An allozyme examination was conducted to study the mating systems and genetic differentiation of populations of Equisetum arvense and E. hyemale. The study revealed that the rate of intragametophytic selfing in these homosporous pteridophytes is very low, i.e., on average 0.020 and 0.019, respectively, despite the potential hermaproditism and selfing of the gametophytes. Most populations consisted of numerous genotypes, and the average heterozygosities of E. arvense and E. hyemale equalled 0.092 and 0.134, respectively. The commonly observed excess of the heterozygote genotypes indicates that there are interclonal differences in the frequency of vegetative reproduction. The level of genetic divergence among populations was considerable even within a limited geographic area. It is suggested that the life history of Equisetum, characterized by the inefficiency of spore germination and gametophyte reproduction in noncolonizing situations, limits the level of gene flow and leads to a great genetic divergence between populations.     

Tuberculosis and Alcoholism

Of 227 chronic alcoholics studied in jail, 20 (9%) had a previous diagnosis of tuberculosis. The chest radiographs of 202 of these inmates were compared with those of 187 inmates serving sentences for other offences. Significant findings compatible with tuberculosis were noted in 34 of 202 (16.8%) chronic alcoholics and in two of 187 (1.1%) other offenders. Tuberculin testing of 98 inmates revealed that 80.6% of the chronic alcoholics and 33.3% of the other offenders had positive skin tests. It is suggested that the mixing in jail of a potentially highly infectious group with susceptible individuals is undesirable and that other methods of management should be considered.     

Immobilized-metal affinity chromatography of serum proteins on gel-immobilized group III A metal ions

The potential pharmacologic use of enzymes has long been considered. Practical applications, however, have been limited by the toxicity and allergic response to administered foreign proteins. A simple in vitro modification that allows the intraperitoneal administration of large doses of L-gulonolactone oxidase to guinea pigs is described. The enzyme is precipitated by guinea pig antisera and reacted with glutaraldehyde (0.125%). The product is comparatively nontoxic in guinea pigs. Administration of this enzyme enables guinea pigs to synthesize ascorbic acid. Success of this approach may depend on reinforcement by the bifunctional reagent of the enzyme-antibody complex.