Association of Leukocyte Telomere Length With Mortality Among Adult Participants in 3 Longitudinal Studies.

Importance: Leukocyte telomere length (LTL) is a trait associated with risk of cardiovascular disease and cancer, the 2 major disease categories that largely define longevity in the United States. However, it remains unclear whether LTL is associated with the human life span.

Objective: To examine whether LTL is associated with the life span of contemporary humans.

Telomeres and the natural lifespan limit in humans.

An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death.

The heritability of leucocyte telomere length dynamics.

Background: Leucocyte telomere length (LTL) is a complex trait associated with ageing and longevity. LTL dynamics are defined by LTL and its age-dependent attrition. Strong, but indirect evidence suggests that LTL at birth and its attrition during childhood largely explains interindividual LTL variation among adults.

Antibodies against interferon-beta in neuromyelitis optica patients.

Neuromyelitis optica (NMO) is an antibody-mediated autoimmune inflammatory disease of the CNS. A poor response to treatment with recombinant interferon beta (IFN-ß) in NMO patients has been suggested, although the precise mechanisms remain uncertain. We analyzed occurrence and clinical consequences of IFN-neutralizing antibodies (NAbs) in 15 IFN-ß treated NMO-patients from a population-based retrospective case series cohort.

Interferon alpha association with neuromyelitis optica.

Interferon-alpha (IFN- α ) has immunoregulatory functions in autoimmune inflammatory diseases. The goal of this study was to determine occurrence and clinical consequences of IFN- α in neuromyelitis optica (NMO) patients. Thirty-six NMO and 41 multiple sclerosis (MS) patients from a population-based retrospective case series were included.

Physical and cognitive functioning of people older than 90 years: a comparison of two Danish cohorts born 10 years apart.

Background: A rapidly increasing proportion of people in high-income countries are surviving into their tenth decade. Concern is widespread that the basis for this development is the survival of frail and disabled elderly people into very old age. To investigate this issue, we compared the cognitive and physical functioning of two cohorts of Danish nonagenarians, born 10 years apart.

The telomere lengthening conundrum--artifact or biology?

Recent longitudinal studies of age-dependent leukocyte telomere length (LTL) attrition have reported that variable proportions of individuals experience LTL lengthening. Often, LTL lengthening has been taken at face value, and authors have speculated about the biological causation of this finding. Based on empirical data and theoretical considerations, we show that regardless of the method used to measure telomere length (Southern blot or quantitative polymerase chain reaction-based methods), measurement error of telomere length and duration of follow-up explain almost entirely the absence of age-dependent LTL attrition in longitudinal studies.

Tracking and fixed ranking of leukocyte telomere length across the adult life course.

Short leukocyte telomere length (LTL) is associated with atherosclerosis in adults and diminished survival in the elderly. LTL dynamics are defined by LTL at birth, which is highly variable, and its age-dependent attrition thereafter, which is rapid during the first 20 years of life. We examined whether age-dependent LTL attrition during adulthood can substantially affect individuals' LTL ranking (e.

Modifications of longitudinally extensive transverse myelitis and brainstem lesions in the course of neuromyelitis optica (NMO): a population-based, descriptive study.

Background: Neuromyelitis optica (NMO) includes transverse myelitis, optic neuritis and brain lesions. Recent studies have indicated that the brainstem is an important site of attack in NMO. Longitudinally extensive transverse myelitis (LETM) is an important component of the clinical diagnosis of NMO.

Heritability of health-related quality of life: SF-12 summary scores in a population-based nationwide twin cohort.

Aim: The present study aims to estimate the relative importance of genetic and environmental factors for health-related quality of life (HRQL) measured by the 12-item Short-Form Health Survey (SF-12).

Methods: The study was based on two Danish twin cohorts (46,417 twin individuals) originating from the nationwide, population-based Danish Twin Registry. The twins were approached by a mailed-out questionnaire in 2002.

Leukocyte telomere dynamics in the elderly.

Limited data suggest that leukocytes of the elderly display ultra-short telomeres. It was reported that in some elderly persons leukocyte telomere length (LTL) shows age-dependent elongation. Using cross-sectional and longitudinal models, we characterized LTL dynamics in participants of the Longitudinal Study of Aging Danish Twins.

The relationship between HbA1c and fasting plasma glucose in patients with increased plasma liver enzyme measurements.

Background: HbA(1c) is currently being introduced for diagnostic purpose in diabetes. Previous studies have, however, indicated that patients with liver disease have false low HbA(1c) levels. We therefore investigated the correlation between HbA(1c) and plasma glucose in patients with different levels of increased liver enzyme concentrations.

Functional characteristics of N8, a new recombinant FVIII.

  The aim of this study was to evaluate the in vitro function of the new recombinant factor VIII (FVIII) compound, N8. The specific activity of N8 as measured in a FVIII:C one-stage clot assay was 9300±400 IU mg(-1) based on the analysis of seven individual batches. The ratio between the FVIII:C activity measured in clot and chromogenic assays was 1.

Recombinant coagulation factor VIIa--from molecular to clinical aspects of a versatile haemostatic agent.

Recombinant factor VIIa (rFVIIa, NovoSeven) is currently the only bypassing agent produced by recombinant technology for the treatment of haemophiliacs whose disease is complicated by inhibitory antibodies. In addition, recombinant production of FVIIa has made it widely available for a variety of purposes and accelerated the growth of our knowledge about FVIIa by generating an abundance of clinical and biochemical data. This fascinating molecule has turned out to be a safe haemostatic agent with great potential in the clinic and has inspired the generation of improved variants currently in (pre-)clinical testing.

Purification and characterization of a new recombinant factor VIII (N8).

A new recombinant factor VIII (FVIII), N8, has been produced in Chinese hamster ovary (CHO) cells. The molecule consists of a heavy chain of 88 kDa including a 21 amino acid residue truncated B-domain and a light chain of 79 kDa. The two chains are held together by non-covalent interactions.

More than one intracellular processing bottleneck delays the secretion of coagulation factor VII.

Coagulation factor VII (FVII) is a vitamin K-dependent glycoprotein that undergoes extensive post-translational modification prior to secretion. Secretion of FVII proteins from producer cells is a slow process. To identify bottlenecks for the transport of FVII through the secretory pathway of FVII-producing cells, we analysed the processing of intracellular FVII by pulse-chase of FVII producing CHO cells followed by radioimmuno precipitation, SDS-PAGE, and autoradiography.

All post-translational modifications except propeptide cleavage are required for optimal secretion of coagulation factor VII.

Human coagulation factor VII (FVII) has two N-glycosylation sites (N145 and N322) and two O-glycosylation sites (S52 and S60). In transiently transfected COS-7 cells, all combinations of N- and O-glycosylation knock-out mutations reduced the release of FVII to the medium. Pulse-chase analysis of CHO-K1 cell lines expressing recombinant FVII demonstrated that virtually all wild-type FVII synthesized was secreted from the cells, whereas both N- and O-glycosylation knock-out mutations induced partial intracellular degradation of the synthesized FVII.

Posttranslational N-glycosylation takes place during the normal processing of human coagulation factor VII.

N-glycosylation is normally a cotranslational process that occurs during translocation of the nascent protein to the endoplasmic reticulum. In the present study, however, we demonstrate posttranslational N-glycosylation of recombinant human coagulation factor VII (FVII) in CHO-K1 and 293A cells. Human FVII has two N-glycosylation sites (N145 and N322).

Isolation of a spontaneously fusing BC3H1 muscle cell line: fusion alters the response to serum stimulation.

Differentiation of skeletal muscle cells involves two distinct events: exit from the cell cycle and expression of muscle-specific contractile genes and formation of multinucleated myocytes. Although many studies have shown that growth factors regulate the initial step of differentiation, little is known about regulation of fusion. BC3H1 cells are a skeletal muscle cell line characterized by a nonfusing phenotype and an ability to dedifferentiate.

Expression of fibroblast growth factor family during postnatal skeletal muscle hypertrophy.

The potential role of the fibroblast growth factor (FGF) family during stretch-induced postnatal skeletal muscle hypertrophy was analyzed by using an avian wing-weighting model. After 2 or 11 days of weighted stretch, anterior latissimus dorsi (ALD) muscles were, on average, 34 (P < 0.01) and 85% (P < 0.