Telomere attrition and accumulation of senescent cells in cultured human endothelial cells

The human umbilical vein endothelial cell (HUVEC) is an important model of the human endothelium that is widely used in vascular research. HUVECs and the adult endothelium share many characteristics including progression into senescence as the cells age. Despite this, the shortening of telomeres and its relationship to the progression into senescence are poorly defined in HUVECs. In this study of several HUVEC lines we show notable consistency in their growth curves. There is a steady decline in the growth rate of HUVECs grown continually in culture and we estimate complete cessation of growth after approximately 70 population doublings. The HUVECs lose telomeric DNA at a consistent rate of 90 base pairs/population doubling and show a progressive accumulation of shortened telomeres (below 5 kilobases). This telomeric loss correlates with the accumulation of senescent HUVECs in culture as assessed by staining for beta-galactosidase activity at pH 6. Although the telomere length of a large population of cells is a relatively crude measure, we suggest that in HUVECs a mean telomere length (as measured by terminal restriction fragment length) of 5 kilobases is associated with entry into senescence. These data demonstrate the strong relationship between telomere attrition and cell senescence in HUVECs. They suggest that DNA damage and subsequent telomere attrition are likely to be key mechanisms driving the development of endothelial senescence in the pathogenesis of vascular disease.     

Telomere attrition predicts reduced survival in a wild social bird,but short telomeres do not

Attempts to understand the causes of variation in senescence trajectories would benefit greatly from biomarkers that reflect the progressive declines in somatic integrity (SI) that lead to senescence. While telomere length has attracted considerable interest in this regard, sources of variation in telomere length potentially unrelated to declines in SI could, in some contexts, leave telomere attrition rates a more effective biomarker than telomere length alone. Here, we investigate whether telomere length and telomere attrition rates predict the survival of wild white‐browed sparrow‐weaver nestlings (Plocepasser mahali). Our analyses of telomere length reveal counterintuitive patterns: telomere length soon after hatching negatively predicted nestling survival to fledging, a pattern that appears to be driven by differentially high in‐nest predation of broods with longer telomeres. Telomere length did not predict survival outside this period: neither hatchling telomere length nor telomere length in the mid‐nestling period predicted survival from fledging to adulthood. Our analyses using within‐individual telomere attrition rates, by contrast, revealed the expected relationships: nestlings that experienced a higher rate of telomere attrition were less likely to survive to adulthood, regardless of their initial telomere length and independent of effects of body mass. Our findings support the growing use of telomeric traits as biomarkers of SI, but lend strength to the view that longitudinal assessments of within‐individual telomere attrition since early life may be a more effective biomarker in some contexts than telomere length alone.     

Pneumonia due to Enterobacter cancerogenus infection

Enterobacter cancerogenus (formerly known as CDC Enteric Group 19; synonym with Enterobacter taylorae) has rarely been associated with human infections, and little is known regarding the epidemiology and clinical significance of this organism. We describe a community-acquired pneumonia case in a 44-year-old female due to E. cancerogenus. Identification and antimicrobial susceptibility of the microorganism was performed by the automatized VITEK 2 Compact system (bioMerieux, France). The clinical case suggests that E. cancerogenus is a potentially pathogenic microorganism in determined circumstances; underlying diseases such as bronchial asthma, empiric antibiotic treatment, wounds, diagnostic, or therapeutic instruments.     

Telomere attrition and growth: a life‐history framework and case study in common terns

The relationship between growth and age‐specific telomere length, as a proxy of somatic state, is increasingly investigated, but observed patterns vary and a predictive framework is lacking. We outline expectations based on the assumption that telomere maintenance is costly and argue that individual heterogeneity in resource acquisition is predicted to lead to positive covariance between growth and telomere length. However, canalization of resource allocation to the trait with a larger effect on fitness, rendering that trait relatively invariant, can cause the absence of covariance. In a case study of common tern (Sterna hirundo) chicks, in which hatching order is the main determinant of variation in resource acquisition within broods, we find that body mass, but not telomere length or attrition, varies with hatching order. Moreover, body mass and growth positively predict survival to fledging, whereas telomere length and attrition do not. Using a novel statistical method to quantify standardized variance in plasticity, we estimate between‐individual variation in telomere attrition to be only 12% of that of growth. Consistent with the relative invariance of telomere attrition, we find no correlation between age‐specific body mass or growth and telomere attrition. We suggest that common tern chicks prioritize investment in long‐term somatic state (as indicated by canalization of telomere maintenance) over immediate survival benefits of growth as part of an efficient brood reduction strategy that benefits the parents. As such, interspecific variation in the growth–telomere length relationship may be explained by the extent to which parents benefit from rapid mortality of excess offspring.     

Bronchopulmonary infection due to Branhamella catarrhalis.

Over six months Branhamella catarrhalis was isolated in pure culture from the sputum of 81 patients with symptoms of acute respiratory tract infection. Of 38 patients who were infected in the community, over half required admission to hospital. The remaining 43 patients acquired the infection in hospital. Forty one of the 81 isolates produced beta-lactamase, 24 of these being hospital acquired infections. As a result 40% of patients who were treated with ampicillin did not respond. Most patients had chronic lung diseases or lung cancer or were taking corticosteroids. Three patients died and one required assisted ventilation; strains producing beta-lactamase were isolated in each case. Acute bronchitis developed in one previously healthy young non-smoker. It is concluded that B catarrhalis is an important pathogen of the lower respiratory tract which should be reported, and strains producing beta-lactamase should be identified. Otherwise, treatment with inappropriate antibiotics may result in increased morbidity or mortality.     

Secondary amyloidosis due to Schistosoma mansoni infection.

Four children with Schistosoma mansoni infection and the nephrotic syndrome with varying degrees of renal dysfunction were found on histological examination to have amyloidosis. In one boy who had no evidence of renal failure complete clinical regression of his nephrotic syndrome and almost complete disappearance of renal amyloid deposits followed adequate treatment of his schistosomal infection. Conditions known to cause secondary amyloidosis were excluded in all four patients. Amyloidosis in association with mansoni infection is probably more common than is currently recognised. Early treatment of the infection, before renal function becomes impaired, may result in regression of the amyloidosis.     

Telomere dynamics in response to chemotherapy

The use of chemotherapy provides an essential arm in the treatment of a number of cancers. The biological feature common to all cancerous cells that sensitizes them to chemotherapeutic agents is their elevated division rate. Rapidly dividing cells, such as tumor cells, are more sensitive to chemotherapeutic agents that act to initiate pathways leading to cell death, a process enhanced in cells with compromised DNA damage responses. The toxicity accompanying chemotherapy is due to side-effects induced in normal regenerative tissues which also have relatively high replication rates, such as hair follicles, the hematopoietic system, the gastrointestinal system, the germline and skin cells. While the side-effects of chemotherapy may be tolerated by the patient, the long term impact of the cytotoxic effects of chemotherapy on healthy tissues is only now becoming apparent. Chemotherapy-induced cytotoxicity in regenerative tissues requires multiple cell divisions in order to reconstitute the affected tissues. At least in part as a consequence of these extra divisions, telomeres in individuals treated with chemotherapy are shorter than age-matched control individuals who have never been exposed to these drugs. Given the essential role of telomeres in regulating cellular aging and chromosomal stability, it is possible that the prematurely shortened telomeres that arise following chemotherapy may impact the long-term replicative potential of these tissues. This review is focused on how telomeres may be modulated, directly or indirectly, by anticancer drugs and the potential long-term consequences of accelerated telomere shortening in healthy tissue as a result of current cancer treatment protocols.     

Hospital infection due to Pseudomonas aeruginosa in resuscitation departments

The bacteriological survey of resuscitation and intensive care units has revealed the presence of P. aeruginosa strains in the microflora in 69.4% of cases. The circulation of 1-2 P. aeruginosa strains, identical in their serovar and pyocin type, is indicative of the presence of hospital infection and, therefore, the endogenous character of the contamination of patients. P. aeruginosa hospital strains are the main causative agents of infectious complications in the patients treated in resuscitation units.