Platelet-induced differentiation of endothelial progenitor cells

Endothelial progenitor cells (EPCs) have the potential to home at sites of vascular lesions and to contribute to revascularization. This homing is a highly concerted mechanism, which involves chemotaxis, adhesion, migration, and finally integration of the cells into the target tissue. Only recently has the platelet been identified as a central mediator of EPC homing. Adherent platelets were able to mediate chemotaxis and adhesion of EPCs, a process that involved P-selectin glycoprotein ligand 1 and very late antigen-4 (VLA-4). Recent studies suggest that platelet-derived stromal cell-derived factor-1 is also involved centrally in the recruitment of EPCs. Furthermore, platelets induce progenitor cell migration by platelet-derived growth factor AB. Recent in vivo data confirm the recruitment of EPCs to sites of vascular lesions after vessel denudation by activated platelets and fibrin. Moreover, when coincubated with platelets, EPCs differentiate to mature endothelial cells and have the potential to migrate and colonize a platelet thrombus. The described interaction of EPCs with platelets represents a novel mechanism of vascular remodeling and healing of endothelial lesions.     

Multi-slice cardiac computed tomography reveals anomalous origin of the right coronary artery between the great arteries

We report a case of a 72-year-old man whose multi-slice cardiac computed tomography revealed an anomalous origin of the right coronary artery between the great arteries.     

Individualized antithrombotic therapy in high risk patients after coronary stenting. A double-edged sword between thrombosis and bleeding

Dual antiplatelet therapy with aspirin and clopidogrel is currently the standard therapy after coronary stent implantation to prevent a life-threatening stent thrombosis. However, a variety of procedural and individual factors contribute to the individual patient risk and have to be taken into account to allow for an individual recommendation for both the duration and intensity of the antiplatelet therapy. Obviously, the benefit of the prevention of stent thrombosis by antithrombotic therapy has to outweigh the risk of severe bleeding complications. Depending on the individual clinical situation and procedural characteristics (stent type, length, angiographic result etc.), the recommended duration of the combined antiplatelet therapy currently varies from four weeks to at least one year. These recommendations are mainly based on large, prospective, randomized trials and evidence-based guidelines. However, in a subgroup of high-risk patients there is insufficient evidence for the benefit of conventional dual antiplatelet regimen. These include i) patients with an indication for anticoagulation, ii) patients with urgent need for an operation requiring a perioperative withholding of antiplatelet therapy, as well as iii) clopidogrel low responders. This review aims to provide a stratification to define patient collectives who may benefit from more individualized antithrombotic regimens on behalf of currently available literature and guidelines.     

Decreased CXCL12 (SDF-1) plasma levels in early Alzheimer's disease: a contribution to a deficient hematopoietic brain support?

The chemokine CXCL12 (also known as stromal cell-derived factor 1, SDF-1) controls many aspects of bone marrow-derived stem cell functions and has been associated with neurogenesis as well with recruitment of brain resident and non-resident circulating cells towards sites of lesion in the central nervous system (CNS). Disrupting this line of chemokine-mediated intercellular communication may contribute to the pathogenesis of Alzheimer's disease (AD). In this study, decreased CXCL12 plasma levels in patients with early AD (p = 0.003) were found, which significantly inversely correlated with CSF tau protein levels (r = -0.373; p = 0.042) and positively with CXCL12 CSF levels (r = 0.429; p = 0.018) and with changes of cognitive functions over the time period of 15 months (r = 0.583; p = 0.009). Our findings indicate a lack of chemotactic activity in early AD and support the view of a deficient regenerative hematopoietic brain support in early AD with putative pathogenic and therapeutic relevance.     

Pitfalls in diagnostics of hip pain: osteoid osteoma and osteoblastoma

Osteoid osteoma and osteoblastoma are benign bone tumors that occur most often in adolescents and predominantly in males. Typical clinical symptoms, such as reduced range of motion of adjacent joints, nocturnal bone pain and relief of pain using non-steroidal anti-inflammatory drug therapy especially in osteoid osteoma may lead to the correct diagnosis. However, these symptoms are not always apparent and specific. In radiographic examinations, the initial changes are often uncharacteristic causing further delay in diagnosis. Magnetic resonance imaging is increasingly used for screening, but early findings in the course of disease might not lead to the definite diagnosis. Both entities (especially osteoid osteoma) occur frequently in the area of the hip. To demonstrate pitfalls in the diagnostic pathway of hip pain caused by benign bone tumors, we present two cases with osteoid osteoma and one with osteoblastoma.     

1 alpha,25(OH)2D3 inhibits not only Th1 but also Th2 differentiation in human cord blood T cells

Human naive CD4+ T helper (Th) and CD8+ cytotoxic (Tc) T cells, which only produce IL-2, may differentiate into Th1/Tc1- or Th2/Tc2-like lymphocytes, characterized by their cytokine production profile. 1 alpha,25-dihydroxyvitamin D3 (1 alpha, 25(OH)2D3) has been reported to inhibit Th1/Tc1-related, but increase Th2/Tc2-associated cytokines in T cells from adults. In industrialized countries, vitamin D supplementation for prevention of rickets is initiated within the first days of life and continued throughout the entire first year. Epidemiologic studies suggest an association of vitamin D exposure in newborns with the incidence of allergic diseases in later life. This study addresses the effects of 1 alpha, 25(OH)2D3 on Th1/Tc1 versus Th2/Tc2 differentiation in long term cell cultures of (naive) cord blood T lymphocytes. Our results show that in CD4+ as well as CD8+ cord blood cells, 1 alpha, 25(OH)2D3 inhibits not only IL-12-generated IFN-gamma production, but also suppresses IL-4 and IL-13 expression induced by IL-4. Thus, in cord blood 1 alpha, 25(OH)2D3 induces a T cell population without predominance of Th2 related cytokines.     

Reversible contraction by looping of the Tcra and Tcrb loci in rearranging thymocytes

Reversible contraction of immunoglobulin loci juxtaposes the variable (V) genes next to the (diversity)-joining-constant ((D)JC) gene domain, thus facilitating V-(D)J recombination. Here we show that the T cell receptor beta (Tcrb) and T cell receptor alphadelta (Tcra-Tcrd) loci also underwent long-range interactions by looping in double-negative and double-positive thymocytes, respectively. Contraction of the Tcrb and Tcra loci occurred in rearranging thymocytes and was reversed at the next developmental stage. Decontraction of the Tcrb locus probably prevented further V(beta)-DJ(beta) rearrangements in double-positive thymocytes by separating the V(beta) genes from the DJC(beta) domain. In most double-negative cells, one Tcrb allele was recruited to pericentromeric heterochromatin. Such allelic positioning may facilitate asynchronous V(beta)-DJ(beta) recombination. Hence, pericentromeric recruitment and locus 'decontraction' seem to contribute to the initiation and maintenance of allelic exclusion at the Tcrb locus.     

Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch

CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using T cell-specific gene ablation of the Notch effector RBP-J or the Notch1 and 2 receptors, we showed here that Notch was required on CD4(+) T cells for physiological Th2 responses to parasite antigens. GATA-3 was necessary for Notch-induced Th2 differentiation, and we identified an upstream Gata3 promoter as a direct target for Notch signaling. Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, Gata3 is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch.