Systemically transferred hematopoietic stem cells home to the subretinal space and express RPE-65 in a mouse model of retinal pigment epithelium damage

Stem cell regeneration of damaged tissue has recently been reported in many different organs. Since the loss of retinal pigment epithelium (RPE) in the eye is associated with a major cause of visual loss - specifically, age-related macular degeneration - we investigated whether hematopoietic stem cells (HSC) given systemically can home to the damaged subretinal space and express markers of RPE lineage. Green fluorescent protein (GFP) cells of bone marrow origin were used in a sodium iodate (NaIO(3)) model of RPE damage in the mouse. The optimal time for adoptive transfer of bone marrow-derived stem cells relative to the time of injury and the optimal cell type [whole bone marrow, mobilized peripheral blood, HSC, facilitating cells (FC)] were determined by counting the number of GFP(+) cells in whole eye flat mounts. Immunocytochemistry was performed to identify the bone marrow origin of the cells in the RPE using antibodies for CD45, Sca-1, and c-kit, as well as the expression of the RPE-specific marker, RPE-65. The time at which bone marrow-derived cells were adoptively transferred relative to the time of NaIO(3) injection did not significantly influence the number of cells that homed to the subretinal space. At both one and two weeks after intravenous (i.v.) injection, GFP(+) cells of bone marrow origin were observed in the damaged subretinal space, at sites of RPE loss, but not in the normal subretinal space. The combined transplantation of HSC+FC cells appeared to favor the survival of the homed stem cells at two weeks, and RPE-65 was expressed by adoptively transferred HSC by four weeks. We have shown that systemically injected HSC homed to the subretinal space in the presence of RPE damage and that FC promoted survival of these cells. Furthermore, the RPE-specific marker RPE-65 was expressed on adoptively transferred HSC in the denuded areas.

Prosthetic treatment planning on the basis of scientific evidence

The objective of this report is to summarize the results on survival and complication rates of different designs of fixed dental prostheses (FDP) published in a series of systematic reviews. Moreover, the various parameters for survival and risk assessment are to be used in attempt to perform treatment planning on the basis of scientific evidence. Three electronic searches complemented by manual searching were conducted to identify prospective and retrospective cohort studies on FDP and implant-supported single crowns (SC) with a mean follow-up time of at least 5 years. Patients had to have been examined clinically at the follow-up visit. Failure and complication rates were analyzed using random-effects Poisson regression models to obtain summary estimates of 5- and 10-year survival proportions. Meta-analysis of the studies included indicated an estimated 5-year survival of conventional tooth-supported FDP of 93.8%, cantilever FDP of 91.4%, solely implant-supported FDP of 95.2%, combined tooth-implant-supported FDP of 95.5% and implant-supported SC of 94.5% as well as resin-bonded bridges 87.7%. Moreover, after 10 years of function the estimated survival decreased to 89.2% for conventional FDP, to 80.3% for cantilever FDP, to 86.7% for implant-supported FDP, to 77.8% for combined tooth-implant-supported FDP, to 89.4% for implant-supported SC and to 65% for resin-bonded bridges. When planning prosthetic rehabilitations, conventional end-abutment tooth-supported FDP, solely implant-supported FDP or implant-supported SC should be the first treatment option. Only as a second option, because of reasons such as financial aspects patient-centered preferences or anatomical structures cantilever tooth-supported FDP, combined tooth-implant-supported FDP or resin-bonded bridges should be chosen.

Human intestinal maltase-glucoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity

Human maltase-glucoamylase (MGAM) is one of the two enzymes responsible for catalyzing the last glucose-releasing step in starch digestion. MGAM is anchored to the small-intestinal brush-border epithelial cells and contains two homologous glycosyl hydrolase family 31 catalytic subunits: an N-terminal subunit (NtMGAM) found near the membrane-bound end and a C-terminal luminal subunit (CtMGAM). In this study, we report the crystal structure of the human NtMGAM subunit in its apo form (to 2.0 A) and in complex with acarbose (to 1.9 A). Structural analysis of the NtMGAM-acarbose complex reveals that acarbose is bound to the NtMGAM active site primarily through side-chain interactions with its acarvosine unit, and almost no interactions are made with its glycone rings. These observations, along with results from kinetic studies, suggest that the NtMGAM active site contains two primary sugar subsites and that NtMGAM and CtMGAM differ in their substrate specificities despite their structural relationship. Additional sequence analysis of the CtMGAM subunit suggests several features that could explain the higher affinity of the CtMGAM subunit for longer maltose oligosaccharides. The results provide a structural basis for the complementary roles of these glycosyl hydrolase family 31 subunits in the bioprocessing of complex starch structures into glucose.

The exchange of radiotherapy data as part of an electronic patient-referral system

PURPOSE: To describe the implementation and use of an electronic patient-referral system as an aid to the efficient referral of patients to a remote and specialized treatment center. METHODS AND MATERIALS: A system for the exchange of radiotherapy data between different commercial planning systems and a specially developed planning system for proton therapy has been developed through the use of the PAPYRUS diagnostic image standard as an intermediate format. To ensure the cooperation of the different TPS manufacturers, the number of data sets defined for transfer has been restricted to the three core data sets of CT, VOIs, and three-dimensional dose distributions. As a complement to the exchange of data, network-wide application-sharing (video-conferencing) technologies have been adopted to provide methods for the interactive discussion and assessment of treatments plans with one or more partner clinics. RESULTS: Through the use of evaluation plans based on the exchanged data, referring clinics can accurately assess the advantages offered by proton therapy on a patient-by-patient basis, while the practicality or otherwise of the proposed treatments can simultaneously be assessed by the proton therapy center. Such a system, along with the interactive capabilities provided by video-conferencing methods, has been found to be an efficient solution to the problem of patient assessment and selection at a specialized treatment center, and is a necessary first step toward the full electronic integration of such centers with their remotely situated referral centers.

Family change theory: A preliminary evaluation on the basis of recent cross-cultural studies

Family change theory (Kagitcibasi, 1996, 2007) is an approach which can be used to explain how modernisation and globalisation processes affect the family. The most important assumption of the theory is that when traditional interdependent cultures modernise, they need not necessarily develop in the direction of the independent family model typical of Western individualistic societies. Instead, they may develop towards a family model of emotional interdependence that combines continuing emotional interdependencies in the family with declining material interdependencies and with rising personal autonomy. In this chapter a preliminary evaluation of the empirical status of family change theory is given based on a review of recent cross-cultural studies. It will be shown to what extent the few studies that have been systematically conducted in this respect have found results either supporting or not supporting aspects ofthe theory, and where the strengths and problems of this research lie.