Mesenchymal Differentiation and Organ Distribution of Established Human Stromal Cell Lines in NOD/SCID Mice

Two human stromal cell lines were established previously from bone marrow-derived primary long-term cultures by immortalization using the SV40 large T antigen and cellular cloning. After irradiation, the fibroblast-like cell lines L87/4 and L88/5 support hematopoietic differentiation of allogeneic cord blood cells in vitro. The stromal cells do not express CD34 and CD50, but some adhesion molecules and integrins, such as CD44, CD54 and CD58. Their expression profiles on RNA and protein levels are suggestive of their osteogenic potency. The quality and quantity of osteocalcin and osteopontin protein expression depended on the culture conditions. Expression of the osteogenic markers increased over time in culture, especially in cells growing in clusters. The stromal cells also expressed collagens I and V, but did not show any expression of collagens II and III. The potentially osteoblastic stromal cells were transplanted into NOD/SCID recipient mice by intravenous injection and were found in various mesenchymal organs up to 10 weeks after transplantation. Osteocalcin-positive human stromal cells could be detected in the bone marrow, thymus, liver, brain and gut of the recipient animals. In summary, there is evidence that human bone-marrow-derived stromal cells have to be considered mesenchymal progenitors, persistently expressing osteogenic markers in vitro and in vivo. Copyright (C) 2001 S, Karger AG, Basel

Measuring chronic stress exposure incorporating the active and healthy ageing (AHA) concept within the cross-sectional Bern cohort study 2014 (BeCS-14).

The aim of the study was to represent chronic stress exposure by a complex generic Active and Healthy (AHA) diagnostic assessment tool incorporating ICF. This is a single-centre, cross-sectional, observational, non-interventional, non-randomized trial in University based women's hospital, division of Gynecological Endocrinology and Reproductive Medicine. All participants followed a standardized, holistic battery of biopsychosocial assessments consisting of bio-functional status (BFS), bio-functional age (BFA) and the questionnaire for chronic stress exposure (TICS). 624 non-pediatric, non-geriatric subjects were recruited in the BeCS-14 cohort. The mean difference between chronological age and BFA was 7.8 ± 8.0 year equivalents. The mean stress level score assessed by SSCS was 13.2 with 45.4% being exposed to above average stress intensity. 22 BFS items (14 objective, 7 subjective) significantly correlated with chronic stress exposure (TICS-SSCS). The constructed sum score composed of SOC_L9 and complaint questionnaire (physical and emotional wellbeing) represented chronic stress exposure best (pearson-correlation value 0.564, p < 0.0001). Higher chronic stress exposure was associated with bio-functional pro-aging (less vitality) in both sexes. In conclusion, chronic stress is accepted as a major risk factor for developing non-communicable diseases (NCD). Our ICF compatible, complex, generic BFS/BFA assessment tool reflects chronic stress exposure and may be applied in various health care settings, e.g., in health promotion and prevention of NCDs

The first three-dimensional visualization of a thrombus in transit trapped between the leads of a permanent dual-chamber pacemaker: a case report

<p>Abstract</p> <p>Introduction</p> <p>Two-dimensional echocardiography is a useful tool in diagnosing cardiac masses. However, the three-dimensional offline reconstruction technique of transesophageal echocardiography might be superior to two-dimensional transesophageal echocardiography in providing additional information of structural details.</p> <p>Case presentation</p> <p>We report the case of a 76-year-old Caucasian man with a permanent dual-chamber pacemaker and a worm-like right-heart thrombus in transit. Two-dimensional transthoracic echocardiography and two-dimensional transesophageal echocardiography showed that it was debatable as to whether "the worm" was originating from the leads. Offline three-dimensional transesophageal echocardiography reconstruction technique proved superior in identifying the cardiac mass as a thrombus trapped between the leads of the pacemaker. The thrombus was successfully dissolved by systemic heparin therapy.</p> <p>Conclusions</p> <p>The three-dimensional transesophageal echocardiography is useful and effective in patients with implanted pacemakers or defibrillators when other closely competing imaging modalities are contraindicated, such as magnetic resonance imaging. In patients with pacemakers and trapped thrombus in transit for whom surgical therapy might be a high risk, medical therapy seems to offer a safer and convincing alternative. Whether the management of right-heart thrombi has to be modified due to the presence of pacemaker leads is controversial.</p

ARVC-Related Mutations in Divergent Region 3 Alter Functional Properties of the Cardiac Ryanodine Receptor

Two single-nucleotide polymorphisms in the type 2 ryanodine receptor (RyR2) leading to the nonsynonymous amino acid replacements G1885E and G1886S are associated with arrhythmogenic right ventricular cardiomyopathy in patients who are carrying both of the corresponding RyR2 alleles. The functional properties of HEK293 cell lines isogenically expressing RyR2 mutants associated with arrhythmogenic right ventricular cardiomyopathy, RyR2-G1885E, RyR2-G1886S, RyR2-G1886D (mimicking a constitutively phosphorylated Ser1886), and the double mutant RyR2-G1885E/G1886S were investigated by analyzing the intracellular Ca2+ release activity resulting from store-overload-induced calcium release. The substitution of serine for Gly1886 caused a significant increase in the cellular Ca2+ oscillation activity compared with RyR2 wild-type-expressing HEK293 cells. It was even more pronounced if glycine 1885 or 1886 was replaced by the acidic amino acids glutamate (G1885E) or aspartate (G1886D). Surprisingly, when both substitutions were introduced in the same RyR2 subunit (RyR2-G1885E/G1886S), the store-overload-induced calcium release activity was nearly completely abolished, although the Ca2+ loading of the intracellular stores was markedly enhanced, and the channel still displayed substantial Ca2+ release on stimulation by 5 mM caffeine. These results suggest that the adjacent glycines 1885 and 1886, located in the divergent region 3, are critical for the function and regulation of RyR2

Frequent and sex-biased deletion of SLX4IP by illegitimate V(D)J-mediated recombination in childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) accounts for ∼25% of pediatric malignancies. Of interest, the incidence of ALL is observed ∼20% higher in males relative to females. The mechanism behind the phenomenon of sex-specific differences is presently not understood. Employing genome-wide genetic aberration screening in 19 ALL samples, one of the most recurrent lesions identified was monoallelic deletion of the 5′ region of SLX4IP. We characterized this deletion by conventional molecular genetic techniques and analyzed its interrelationships with biological and clinical characteristics using specimens and data from 993 pediatric patients enrolled into trial AIEOP-BFM ALL 2000. Deletion of SLX4IP was detected in ∼30% of patients. Breakpoints within SLX4IP were defined to recurrent positions and revealed junctions with typical characteristics of illegitimate V(D)J-mediated recombination. In initial and validation analyses, SLX4IP deletions were significantly associated with male gender and ETV6/RUNX1-rearranged ALL (both overall P < 0.0001). For mechanistic validation, a second recurrent deletion affecting TAL1 and caused by the same molecular mechanism was analyzed in 1149 T-cell ALL patients. Validating a differential role by sex of illegitimate V(D)J-mediated recombination at the TAL1 locus, 128 out of 1149 T-cell ALL samples bore a deletion and males were significantly more often affected (P = 0.002). The repeatedly detected association of SLX4IP deletion with male sex and the extension of the sex bias to deletion of the TAL1 locus suggest that differential illegitimate V(D)J-mediated recombination events at specific loci may contribute to the consistent observation of higher incidence rates of childhood ALL in boys compared with girl

Evidence for a Pathogenic Role of Different Mutations at Codon 188 of PRNP

Clinical and pathological changes in familial Creutzfeldt-Jakob disease (CJD) cases may be similar or indistinguishable from sporadic CJD. Therefore determination of novel mutations in PRNP remains of major importance

Impacts of 1.5°C Global Warming on Natural and Human Systems

An IPCC Special Report on the impacts of global warming of 1.5°C above pre-industrial levels and related global greenhouse gas emission pathways, in the context of strengthening the global response to the threat of climate change, sustainable development, and efforts to eradicate povert