PEKK-made indirect temporary crowns and bridges: a clinical pilot study.

OBJECTIVES: The aim of the present study was to find out whether the high-performance polymer PEKK is an equivalent alternative compared to cobalt chrome (CoCr)-made restorations, regarding to biocompatibility, stability, and comfort. MATERIALS AND METHODS: Twenty-two patients (m, 10; f, 12) who were indicated for a long-term temporary-fixed restoration were included. They were randomized through a lottery procedure into two groups: the first group was restored with veneered PEKK-made crowns and bridges (Pekkton ivory), while the second group was restored with veneered CoCr crowns. Clinical parameters (plaque index (PI), probing depth (PD), fracture, and chipping) were documented in a period of 3-5 months from the insertion of restoration. Furthermore, every patient completed the OHIP-14 questionnaire. An exchange of the restorations from the first to the alternative material was performed after a period of 3-5 months. RESULTS: All patients showed an improvement of the oral hygiene and probing depth after insertion of the temporary restorations. However, there were no significant differences between PEKK and CoCr-made restorations (P > 0.05). There was no chipping after 5 months for both kinds of materials. There was a noticeable reduction of pain and discomfort of patients after insertion of temporary restorations. However, there were no significant differences between the two materials (P > 0.05). CONCLUSIONS: PEKK-made temporary restorations offer a good and stable alternative to CoCr-made restorations. They have a high aesthetical advantage over CoCr restoration. CLINICAL RELEVANCE: Esthetic and price-efficient temporary crowns can be offered for the patient during periodontal therapy to improve its success, in particular by improving the oral hygiene.

Developmental origins of hematopoietic stem cells.

Hematopoietic stem cells (HSCs) are at the foundation of the hematopoietic hierarchy and give rise to all blood lineages in the adult organism. A thorough understanding of the molecular, cellular, and developmental biology of HSCs is of fundamental importance, but is also clinically relevant for the advancement of cell replacement therapies and transplantation protocols in blood-related genetic disease and leukemias. While the major anatomical sites of hematopoiesis change during ontogeny, it was long believed that the developmental origin of the adult mammalian hematopoietic system was the yolk sac. However, current studies have shown that the first adult-type HSCs are autonomously generated in the intrabody portion of the mouse embryo, the aorta-gonads-mesonephros (AGM) region, and sublocalize to the dorsal aorta. HSCs are also found in the other large embryonic vessels, the vitelline and umbilical arteries. The intraluminal hematopoietic clusters along these vessels, together with the role of the Runx1 transcription factor in cluster and HSC formation and the HSC/endothelial/mesenchymal Runxl expression pattern, strongly suggest a vascular endothelial/mesenchymal origin for the first HSCs. Moreover, a transgenic mouse line expressing the GFP marker under the control of the Sca-1 transcriptional regulatory elements (GFP expression marks all HSCs) shows a clear localization of GFP-expressing cells to the endothelial cell layer of the dorsal aorta. Thus, highly enriched GFP-positive AGM HSCs will serve as a basis for the future examination of the cellular and molecular factors involved in the induction and expansion of adult HSCs.

Macrophage inflammatory protein-1alpha uses a novel receptor for primitive hemopoietic cell inhibition.

Macrophage inflammatory protein-1alpha (MIP-1alpha) is a member of the chemokine family of proinflammatory mediators. In addition to its inflammatory roles, MIP-1alpha has been shown to be active as an inhibitor of primitive hemopoietic cell proliferation. Indeed, a dysfunction in this inhibitory process has been postulated to contribute to leukemogenesis. Research has been aimed at characterizing the receptor involved in cellular inhibition by MIP-1alpha. This study demonstrates that of all the beta-chemokines tested, only MIP-1alpha is capable of inhibiting primitive hemopoietic cell proliferation. Because no MIP-1alpha-specific receptors have been identified, this suggests that inhibition is mediated by an uncharacterized receptor. Further evidence for the involvement of a novel receptor in this process is the equivalent potencies of MIP-1alphaS and MIP-1alphaP variants of human MIP-1alpha and the fact that primitive cells from bone marrow derived from individual MIP-1alpha receptor null mice display a full response to MIP-1alpha inhibition.

Aggregation-independent modulation of proteoglycan binding by neutralization of C-terminal acidic residues in the chemokine macrophage inflammatory protein 1alpha.

Members of the chemokine family of proteins mediate their biological effects through interaction with a family of seven-transmembrane G-protein-coupled receptors. This interaction is complicated by the biochemical properties of chemokines, such as their ability to form self aggregates and their ability to bind to proteoglycans. With some chemokines there is a clear interrelationship between these interactions; the chemokine platelet factor 4 binds preferentially to proteoglycans in its aggregated form. Little is known about the role of aggregation in the proteoglycan binding of other chemokines. Here we demonstrate that the aggregation status of the chemokine macrophage inflammatory protein 1alpha (MIP-1alpha) has no detectable effect on its affinity for proteoglycans. Furthermore, we demonstrate that the alteration of acidic amino acid residues in MIP-1alpha influences the affinity of its interactions with heparin as these residues are progressively neutralized, leading to an enhanced binding affinity for heparin. Thus, with MIP-1alpha, aggregation is not a determinant of proteoglycan binding; however, overall charge does seem to have a major role in the interaction. These results therefore add to our understanding of the nature of the interaction between MIP-1alpha and proteoglycans and suggests that the basic amino acids might not be the sole regulators of proteoglycan binding.

Adhesion-dependent tyrosine phosphorylation of (beta)-dystroglycan regulates its interaction with utrophin.

Many cell adhesion-dependent processes are regulated by tyrosine phosphorylation. In order to investigate the role of tyrosine phosphorylation of the utrophin-dystroglycan complex we treated suspended or adherent cultures of HeLa cells with peroxyvanadate and immunoprecipitated (beta)-dystroglycan and utrophin from cell extracts. Western blotting of (&bgr;)-dystroglycan and utrophin revealed adhesion- and peroxyvanadate-dependent mobility shifts which were recognised by anti-phospho-tyrosine antibodies. Using maltose binding protein fusion constructs to the carboxy-terminal domains of utrophin we were able to demonstrate specific interactions between the WW, EF and ZZ domains of utrophin and (beta)-dystroglycan by co-immunoprecipitation with endogenous (beta)-dystroglycan. In extracts from cells treated with peroxyvanadate, where endogenous (beta)-dystroglycan was tyrosine phosphorylated, (beta)-dystroglycan was no longer co-immunoprecipitated with utrophin fusion constructs. Peptide 'SPOTs' assays confirmed that tyrosine phosphorylation of (beta)-dystroglycan regulated the binding of utrophin. The phosphorylated tyrosine was identified as Y(892) in the (beta)-dystroglycan WW domain binding motif PPxY thus demonstrating the physiological regulation of the (beta)-dystroglycan/utrophin interaction by adhesion-dependent tyrosine phosphorylation.

ESkine, a novel beta-chemokine, is differentially spliced to produce secretable and nuclear targeted isoforms.

Using the murine embryonal stem cell system, we have identified a novel gene encoding a highly divergent member of the beta-chemokine family of proinflammatory mediators and have called this protein ESkine. Much of the coding sequence for ESkine overlaps with the 3'-end of a novel interleukin 11 receptor alpha-like sequence on murine chromosome 4. ESkine is produced as two splice variants. One of these variants encodes a classical chemokine with an associated signal peptide, while the other variant (PESKY) possesses the main body of the chemokine but has replaced the signal peptide with an alternative stretch of amino acids that allows for nuclear targeting of this isoform. This differential splicing arises as a result of alternative 5' exon usage. These differentially spliced forms are expressed at discrete tissue loci. Thus, while ESkine is highly expressed in the placenta, PESKY is mainly expressed in the Testes and brain and weakly in the developing embryo. Studies on the proinflammatory properties of ESkine reveal it to be active in inducing polarization of CD4(+) T cells but to be inactive on other hemopoietic cellular populations.