SCF modulates organ distribution and hematopoietic engraftment of CB-derived pluripotent HPC transplanted in NOD/SCID mice

BACKGROUND: During the engraftment process of transplanted HPC, the beta 1 integrins play an important role. An increased expression and adhesive function of these integrins has been shown in hematopoietic cell lines and peripheral blood-derived HPC after stimulation with SCF. In this study, we investigated the influence of SCF on the engraftment capability and tissue distribution of cord blood (CB) cells transplanted into NOD/SCID mice. METHODS: CB-derived mononuclear cells were injected i.v. into 40 sublethally irradiated NOD/SCID mice with or without the addition of 10 microg SCF/ mouse. Six weeks later, BM, liver, kidneys, brain and testicular tissue were analyzed for the prevalence of human cells. RESULTS: The mean proportion of human CD45+ CD71+ cells within the BM of all engrafted mice receiving SCF in addition to the cells was 1.7-fold higher than in the respective controls. By immunohistochemical staining, human cells were found in liver and kidneys of the engrafted animals, but not in neural tissues or testicles. In the kidneys, the proportion of human cells rose significantly from 0.07 +/- 0.3% to 0.24 +/- 0.05% with treatment with SCF, compared with untreated controls. Single human cells in the liver additionally stained positive for human albumin, indicating organ-specific differentiation of the transplanted cells. DISCUSSION: Our results indicate that stimulation with SCF modulates the tissue distribution of the progeny of the transplanted cells and improves the hematopoietic engraftment potential of transplanted CB cells

SINBAD - a proposal for a dedicated accelerator research facility at DESY

A dedicated accelerator research and development facility SINBAD (Short INnovative Bunches and Accelerators at DESY) is proposed. This multi-purpose research facility is initially aimed at promoting three major goals: (1) Short electron bunches for ultra-fast science. (2) Construction of a plasma accelerator module with useable beam quality (3) Setup of an attosecond radiation source with advanced technology. Research and development on these topics is presently ongoing at various places at DESY, as add-on experiments at operational facilities. The two research goals are intimately connected: short bunches and precise femtosecond timing are requirements for developing a plasma accelerator module with external injection or staging. The scientific case of a dedicated facility for accelerator research at DESY is discussed. Further options are mentioned, like the use of a 1 GeV beam from Linac II for FEL studies. The presently planned conversion of the DORIS accelerator and its central halls into the SINBAD facility is described. The available space will allow setting up several independent experiments with a cost-effective use of the same infrastructure(for example a central high power laser, a central timing and synchronization lab, etc.). National and international contributions and proposals can be envisaged. A preliminary, possible layout and the design work plan are discussed

Molecular and clinical spectrum of type I plasminogen deficiency: a series of 50 patients

Severe type I plasminogen (PLG) deficiency has been causally linked to a rare chronic inflammatory disease of the mucous membranes that may be life threatening. Here we report clinical manifestations, PLG plasma levels, and molecular genetic status of the PLG gene of 50 patients. The most common clinical manifestations among these patients were ligneous conjunctivitis (80%) and ligneous gingivitis (34%), followed by less common manifestations such as ligneous vaginitis (8%), and involvement of the respiratory tract (116%), the ears (14%), or the gastrointestinal tract (2%). Four patients showed congenital occlusive hydrocephalus, 2 with Dandy-Walker malformation of cerebellum. Venous thrombosis was not observed. In all patients, plasma PLG levels were markedly reduced. In 38 patients, distinct mutations in the PLG gene were identified. The most common genetic alteration was a K19E mutation found in 34% of patients. Transient in vitro expression of PLG mutants R134K, delK212, R216H, P285T P285A, T319_N320insN, and R776H in transfected COS-7 cells revealed significantly impaired secretion and increased degradation of PLG. These results demonstrate impaired secretion of mutant PLG proteins as a common molecular pathomechanism in type I PLG deficiency.Wo