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F Scherer

Publications and source records attributed to F Scherer.

9 recordsLinked to original sources
PubMed2002

Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo.

Low efficiencies of nonviral gene vectors, the receptor-dependent host tropism of adenoviral or low titers of retroviral vectors limit their utility in gene therapy. To overcome these deficiencies, we associated gene vectors with superparamagnetic nanoparticles and targeted gene delivery by application of a magnetic field. This potentiated the efficacy of any vector up to several hundred-fold, allowed reduction of the duration of gene delivery to minutes, extended the host tropism of adenoviral vectors to nonpermissive cells and compensated for low retroviral titer. More importantly, the high transduction efficiency observed in vitro was reproduced in vivo with magnetic field-guided local transfection in the gastrointestinal tract and in blood vessels. Magnetofection provides a novel tool for high throughput gene screening in vitro and can help to overcome fundamental limitations to gene therapy in vivo.

Adenoviridae↗
PubMed2001

Pharmacokinetics of native Escherichia coli asparaginase (Asparaginase medac) and hypersensitivity reactions in ALL-BFM 95 reinduction treatment.

Repeated asparaginase treatment has been associated with hypersensitivity reactions against the bacterial macromolecule in a considerable number of patients. Immunological reactions may range from anaphylaxis without impairment of serum asparaginase activity to a very fast decline in enzyme activity without any clinical symptoms. Previous investigations on a limited number of patients have shown high interindividual variability of asparaginase activity time courses and hypersensitivity reactions in about 30% of patients during reinduction treatment. Therefore, monitoring of reinduction treatment was performed prospectively in 76 children with newly diagnosed acute lymphoblastic leukaemia (ALL). According to the ALL-Berlin-Frankfurt-Münster (BFM) 95 protocol, 10 000 U/m2 body surface area of native Escherichia coli asparaginase (Asparaginase medac) was given on d 8, 11, 15 and 18. In 45/76 children, trough and peak activities were determined with every dose, and also on d 4 and d 11 after the last administration. Data on asparaginase activity were not available from the remaining 31 patients, but information with regard to hypersensitivity reactions only was given. Eighteen out of 76 patients (24%) suffered a clinical hypersensitivity reaction; however, no silent inactivation was observed. Activity in the therapeutic range of greater than 100 U/l for at least 14 d was determined in 43 of the 45 patients who were analysed for enzyme activity.

Adolescent↗
PubMed1995

LPS directly induces oxygen radical production in human monocytes via LPS binding protein and CD14.

In human monocytes, superoxide (O2-) generation accompanies phagocytosis and is important for bactericidal activity. It also contributes to tissue damage in inflammation. In the present study we investigated, whether lipopolysaccharide (LPS) directly stimulates monocyte O2- production with kinetics known for other LPS effects and, if so, by which mechanism. LPS caused a time- and dose-dependent O2- release in nonadherent purified monocytes. The effect appeared after 5 min, peaked at 30 min, and disappeared after 2 h. It was maximal with 10 ng/ml lipid A (+148 +/- 22%, P < .001), 1 ng/ml LPS Escherichia coli Re (+226 +/- 68%, P < .001), and 100 ng/ml LPS Salmonella abortus equi sm (+272 +/- 52%, P < .001), respectively. The effect was not observed in buffer, even when using 10 micrograms/ml LPS. It was dependent on the presence of heat-inactivated AB serum, with a maximal effect at > or = 0.5%. Serum could be replaced by LPS-binding protein (LBP). Polymyxin B and anti-LBP antiserum, respectively, blocked the LPS effect. LPS-induced O2- generation was also completely blocked by anti-CD14 antibodies (3C10 and 63D3) and by their corresponding F(ab')2 fragments. Monocytes treated with phosphoinositol-specific phospholipase C and monocytes from patients with paroxysmal nocturnal hemoglobinuria, lacking the phosphatidylinositol-anchored CD14, did not respond to LPS stimulation with O2- production. Similarly to LPS, E. coli caused stronger O2- production with heat-inactivated serum than without, and this effect was blocked by anti-CD14 antibodies. In conclusion, these data indicate that LPS directly stimulates O2- production in human monocytes via CD14 depending on LBP.

Acute-Phase Proteins↗
PubMed1973

Histopathology and distribution of viral antigens in hamsters infected with virulent and benign Venezuelan encephalitis viruses.

Lethalities and virulences of Venezuelan encephalitis (VE) viruses for hamsters were found to correlate with severity of histopathologic lesions in hematopoietic and brain tissues. Highly virulent strains (subtype I) destroyed marrow and lymphoid cells rapidly and produced intestinal wall damage; focal brain hemorrhages and destruction of Purkinje cells also occurred within the 4 to 5 days between subcutaneous inoculation and death. Like subtype I virus, a slightly less virulent strain (subtype II) also caused necrosis of bone marrow and brain lesions, but only minimal lymphoid cell damage occurred. The less virulent subtype III VE virus, which killed hamsters between 4 and 14 days after inoculation, usually caused no lesions in hematopoietic tissues, and deaths were related chiefly to hemorrhagic brain lesions and necrosis of Purkinje cells. Two VE viruses, benign for hamsters (the TC-83 attenuated vaccine strain and subtype IV), usually caused no necrosis of hematopoietic or brain tissues; focal extravasations of blood and swollen glial cells were found in brains of the rare hamsters that died. The degrees of necrosis seen in tissues stained with hematoxylin and eosin correlated with the quantities of viral antigens detected by fluorescent antibody, except in pancreas and small intestinal smooth muscle and glands, where antigens of subtype I virus were present without morphologic damage.

Animals↗