Migration and differentiation of myogenic precursors following transplantation into the developing rat brain

There is increasing evidence that muscle-derived precursor cells can, under appropriate conditions, give rise to other than myogenic cell types. Transplantation into the embryonic ventricular zone provides a unique opportunity to study the migration and differentiation of non-neural somatic progenitor cells in response to instructive cues within the developing neuroepithelium. Here, we demonstrate that myogenic cell lines grafted into the ventricles of rat embryos showed widespread migration into several host brain compartments. In contrast to incorporation patterns observed after transplantation of neural cells, grafted myoblasts incorporated virtually exclusively along endogenous blood vessels. Preferential incorporation sites included cortex, olfactory bulb, hippocampus, striatum, thalamus, hypothalamus, and tectum. While the engrafted myoblasts showed no evidence of neural differentiation, a fraction exhibited pronounced coexpression of endothelial marker antigens. These findings support the concept of a close developmental relationship between the myogenic and the endothelial lineages. Used as a delivery system, transfected myoblasts may be exploited for widespread gene transfer to the perivascular compartment of the perinatal central nervous system.     

RGD modified polymers: biomaterials for stimulated cell adhesion and beyond

Since RGD peptides (R: arginine; G: glycine; D: aspartic acid) have been found to promote cell adhesion in 1984 (Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule, Nature 309 (1984) 30), numerous materials have been RGD functionalized for academic studies or medical applications. This review gives an overview of RGD modified polymers, that have been used for cell adhesion, and provides information about technical aspects of RGD immobilization on polymers. The impacts of RGD peptide surface density, spatial arrangement as well as integrin affinity and selectivity on cell responses like adhesion and migration are discussed.     

Possibilities of surgery and their differentiated use in the individual treatment of endometriosis

Numerous medical, surgical, and combined therapies have been proposed in the management of endometriosis. This range of treatment options contrasts remarkably with the evidence regarding their respective proven success rates. An exact preoperative differential diagnosis as well as adherence to operative recommendations that have been established meanwhile are essential for optimal results of surgery.     

Neonatal nucleated red blood cell count and postpartum complications in growth restricted fetuses

AIMS: To study relationships between nucleated red blood cell count (NRBC), persistence of NRBC count elevation and neonatal complications in growth restricted fetuses (IUGR). METHODS: Observational study of IUGR neonates (birthweight < 10th percentile). NRBC's/100 WBC were ascertained in a peripheral blood sample. Subsequent daily samples were analyzed until NRBC's fell < 10/100 WBC. NRBC count and days of NRBC elevation were related to complications (respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotising enterocolitis (NEC), circulatory insufficiency (CI), day 28 oxygen requirement, mortality). RESULTS: 157/298 IUGR neonates (52.7%) had complications, which were associated with a higher NRBC count and persistence of NRBC elevation (12 vs. 189 NRBC's and 1 vs. 4 days; p < 0.0001 respectively). This relationship applied to each complication. Prematurity was the main determinant of RDS, BPD and mortality, while IVH was related to mechanical ventilation, CI to birthweight percentile and NEC to degree of acidemia. Persistence of NRBC count elevation was a statistical contributor for RDS, CI and mortality and the NRBC count to day 28 oxygen requirement. CONCLUSION: NRBC count elevation and persistent NRBC count elevation are associated with perinatal complications in IUGR. Wide ranges in numbers, complex relationships between triggering factors and impacts of other perinatal variables limit the use of NRBC parameters as predictors of complications.     

Assessment of functional gastrointestinal disorders using the Gastro-Questionnaire

The purpose was to investigate the reliability and factorial structure of the Gastro-Questionnaire for the screening and psychometric measurement of functional gastrointestinal disorders (FGDs). The questionnaire contains 27 gastrointestinal symptom items drawn from the Rome—II criteria, which are rated by frequency and severity, as well as some items to exclude organic diseases. The questionnaire was administered to 259 normal participants and to 69 participants of the annual German meeting of patients with irritable bowel syndrome. Reliability was good (Cronbach’s alpha for frequency and severity items: α = .86 and α = .87). Factor analysis yielded a six-factor solution explaining 60.7% of the variance. Diagnostic frequencies ranged from 32.8%to100% for FGDs in general, from 1.3% to 76.8% for irritable bowel syndrome, and from 7.0% to 100% for functional dyspepsia, depending on samples and symptom definitions. The Gastro-Questionnaire is a very economic, reliable, and content-valid instrument for the assessment of FGDs.     

MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo

The susceptibility of certain inbred mouse strains to murine cytomegalovirus (MCMV) is related to their inability to generate a strong natural killer (NK) cell response. We addressed here whether the MCMV susceptibility of the BALB/c strain is due to viral functions that control NK cell activation in a strain-specific manner. MCMV expresses two proteins, gp48 and gp40, that are encoded by the genes m06 and m152, respectively; they down-regulate major histocompatibility complex (MHC) class I expression at the plasma membrane. Using MCMV deletion mutants and revertants, we found that gp40 but not gp48 controls NK cell activation. Absence of gp40 improved antiviral NK cell control in BALB/c, but not C57BL/6, mice. Down-regulation of H-60, the high-affinity ligand for the NKG2D receptor, was the mechanism by which gp40 modulates NK cell activation. Thus, a single herpesvirus protein has a dual function in inhibiting both the adaptive as well as the innate immune response.     

Correction of the iron overload defect in beta-2-microglobulin knockout mice by lactoferrin abolishes their increased susceptibility to tuberculosis

As a resident of early endosomal phagosomes, Mycobacterium tuberculosis is connected to the iron uptake system of the host macrophage. beta-2-microglobulin (beta2m) knockout (KO) mice are more susceptible to tuberculosis than wild-type mice, which is generally taken as a proof for the role of major histocompatibility complex class I (MHC-I)-restricted CD8 T cells in protection against M. tuberculosis. However, beta2m associates with a number of MHC-I-like proteins, including HFE. This protein regulates transferrin receptor mediated iron uptake and mutations in its gene cause hereditary iron overload (hemochromatosis). Accordingly, beta2m-deficient mice suffer from tissue iron overload. Here, we show that modulating the extracellular iron pool in beta2m-KO mice by lactoferrin treatment significantly reduces the burden of M. tuberculosis to numbers comparable to those observed in MHC class I-KO mice. In parallel, the generation of nitric oxide impaired in beta2m-KO mice was rescued. Conversely, iron overload in the immunocompetent host exacerbated disease. Consistent with this, iron deprivation in infected resting macrophages was detrimental for intracellular mycobacteria. Our data establish: (a) defective iron metabolism explains the increased susceptibility of beta2m-KO mice over MHC-I-KO mice, and (b) iron overload represents an exacerbating cofactor for tuberculosis.