Biomedical subjects

Alexander Werner

Publications and source records attributed to Alexander Werner.

4 recordsLinked to original sources

PubMed2006

A prospective study comparing different iodine concentrations for triphasic multidetector row CT of the upper abdomen.

OBJECTIVES: To investigate the effect of different iodine concentrations at either constant injection or iodine administration rates but constant total iodine load on contrast enhancement of liver, pancreas and spleen by multidetector row CT. MATERIALS AND METHODS: One hundred and twenty consecutive patients (70+/-6 years) underwent triphasic liver CT at a four-channel multidetector-row CT using the non-ionic contrast medium iopromide. Patients were divided into six equal groups-I: 150 ml, 240 mg/ml at 4 ml/s; II: 120 ml, 300 mg/ml at 4 ml/s; III: 97.3 ml, 370 mg/ml at 4 ml/s; IV: 150 ml, 240 mg/ml at 5 ml/s; V: 120 ml, 300 mg/ml, 60 ml at 6 ml/s, 60 ml at 3 ml/s; VI: 97.3 ml, 370 mg/ml at 3.3 ml/s. ROIs were measured in the liver, the pancreas, and the spleen in unenhanced, arterial, portal venous, and equilibrium phase. RESULTS: At a constant injection rate of 4 ml/s, pancreatic enhancement over baseline only in the arterial phase was significantly higher at 370 mg/ml (58+/-15 HU versus 59+/-18 HU versus 74+/-20 HU for groups I-III, respectively (p<0.02)). Comparison of different iodine concentrations at constant iodine administration rate (groups II, IV and VI) and of all six protocols revealed no significant differences at either phase. CONCLUSIONS: At a constant iodine load and constant injection rates, the high-iodinated contrast agent iopromide at 370 mg/ml improves pancreatic enhancement in the arterial phase. At constant iodine load and constant iodine administration rates, there is no significant effect of different iodine concentrations.

Aged↗

PubMed2006

Absence of alpha 7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy.

Both the dystrophin-glycoprotein complex and alpha7beta1 integrin have critical roles in the maintenance of muscle integrity via the provision of mechanical links between muscle fibres and the basement membrane. Absence of either dystrophin or alpha7 integrin results in a muscular dystrophy. To clarify the role of alpha7 integrin and dystrophin in muscle development and function, we generated integrin alpha7/dystrophin double-mutant knockout (DKO) mice. Surprisingly, DKO mice survived post-natally and were indistinguishable from wild-type, integrin alpha7-deficient and mdx mice at birth, but died within 24-28 days. Histological analysis revealed a severe muscular dystrophy in DKO mice with endomysial fibrosis and ectopic calcification. Weight loss was correlated with the loss of muscle fibres, indicating that progressive muscle wasting in the double mutant was most likely due to inadequate muscle regeneration. The data further support that premature death of DKO mice is due to cardiac and/or respiratory failure. The integrin alpha7/dystrophin-deficient mouse model, therefore, resembles the pathological changes seen in Duchenne muscular dystrophy and suggests that the different clinical severity of dystrophin deficiency in human and mouse may be due to a fine-tuned difference in expression of dystrophin and integrin alpha7 in both species. Together, these findings indicate an essential role for integrin alpha7 in the maintenance of dystrophin-deficient muscles.

Animals↗

PubMed2003

Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels.

Recently, cationic liposomes have been shown to preferentially target the angiogenic endothelium of tumors. It was the aim of our study to investigate the influence of liposomal surface charge on the uptake and kinetics of liposomes into solid tumors and tumor vasculature. Experiments were performed in the amelanotic hamster melanoma A-Mel-3 growing in the dorsal skinfold chamber preparation of male Syrian golden hamsters. Fluorescently labeled liposomes with different surface charge were prepared. Accumulation of i.v. injected liposomes was assessed by quantitative intravital fluorescence microscopy of tumor and surrounding host tissue. The histological distribution of liposomes was analyzed by double-fluorescence microscopy 20 min after application of fluorescently labeled lectin as a vascular marker. After i.v. application of anionic and neutral liposomes, we observed an almost homogeneous distribution of liposome-induced fluorescence throughout the chamber preparation without specific targeting to tumor tissue. In contrast, cationic liposomes exhibited a significantly enhanced accumulation in tumor tissue and tumor vasculature up to 3-fold compared to surrounding tissue (p<0.05). The histological distribution of neutral and anionic liposomes revealed extravasation 20 min after i.v. injection, while cationic liposomes displayed a highly selective accumulation on the vascular endothelium. In conclusion, cationic liposomes exhibited a preferential uptake in angiogenic tumor vessels and therefore may provide an efficient tool for the selective delivery of diagnostic or therapeutic agents to angiogenic blood vessels of solid tumors. On the other hand, anionic and neutral liposomes may be used as carriers of drugs to the extravascular compartment of tumors due to their extravasation.

Animals↗

PubMed2003

Lymphocyte infiltration in the injured brain: role of proinflammatory cytokines.

Studies using mouse axotomised facial motoneuron model show a strong and highly selective entry of CD3+ lymphocytes into the affected nucleus, with a maximum at Day 14, which coincides with the peak of neuronal cell death, microglial phagocytosis, and increased synthesis of interleukin-1 beta (IL1beta), tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma). We explored the possible involvement of these cytokines during the main phase of lymphocyte recruitment into the axotomised facial motor nucleus 7-21 days after nerve cut using mice homozygously deficient for IL1 receptor type 1 (IL1R1-/-), TNF receptor type 1 (TNFR1-/-), type 2 (TNFR2-/-) and type 1 and 2 (TNFR1&2-/-), IFNgamma receptor type 1 (IFNgammaR1-/-), and the appropriate controls for the genetic background. Transgenic deletion of IL1R1 led to a 54% decrease and that of TNFR2 to a 44% reduction in the number of CD3+ T-cells in the axotomised facial motor nucleus, with a similar relative decrease at Day 7, 14, and 21. Deletion of TNFR1 or IFNgammaR1 had no significant effect. Deletion of both TNFR1 and 2 (TNFR1&2-/-) caused a somewhat stronger, 63% decrease than did TNFR2 deletion alone, but this could be due to an almost complete inhibition of neuronal cell death. No mutations seemed to inhibit aggregation of CD3+ T-cells around glial nodules consisting of Ca-ion binding adaptor protein-1 (IBA1)+ phagocytotic microglia and neuronal debris. Altogether, the current data show the importance of IL1R1 and TNFR2 as the key players during the main phase of lymphocyte recruitment to the damaged part of the central nervous system.

Animals↗