Bromsulfalein-Kinetik mit albumingebundenem BSP

Zusammenfassung Die Beeinflussung der BSP-Kinetik durch Zusätze von Albumin zur Injektionslösung wurde geprüft. Bei einer Dosierung von 5 mg BSP pro kg Körpergewicht bleibt die Eliminationshalbwertzeit bis zu einem BSP-Albuminverhältnis von 1:10 (w/w) unverändert, nach größeren Albumingaben ist sie signifikant verlängert.F.H. Dost zum 65. Geburtstag zugeeignet     

Effect of synthetic lipopeptides formulated in liposomes on the maturation of human dendritic cells

Diacylated (e.g. MALP-2) and triacylated (Pam(3)Cys derivatives) lipopeptides, deriving from the N-terminal moiety of respectively mycoplasmal and E. coli lipoproteins, are powerful adjuvants recognized by Toll-like receptors (TLR) which have been used successfully to trigger cell activation and immune responses. To design liposome-based vaccination constructs in which Th and CTL epitopes are conjugated to synthetic lipopeptide analogues anchored into the bilayers of the vesicles, the peptide moieties of the lipopeptides were functionalized with thiol-reactive groups, such as maleimide (Mal) or bromoacetyl, incorporated into liposomes and reacted with thiol carrying peptide epitopes. Because dendritic cells (DCs) play a key role as antigen-presenting cells in immune responses, in the present study we have evaluated the impact of the functionalization of lipopeptide analogues Pam(2)CAG, Pam(3)CAG and Ol(3)GAG on the phenotypic maturation of human monocyte-derived DCs. The intrinsic cellular activities of the lipopeptide analogues incorporated into liposomes were monitored, in vitro, by measuring the up-regulation of the cell-surface markers CD80, CD83, CD86 and HLA-DR. We found that in some cases their functionalization with thiol-reactive groups led to a loss of activity. The stimulatory potency can be ranked in the following order: Pam(3)CAG>/=Pam(2)CAG-Mal-Th approximately Pam(2)CAG-Mal>Pam(3)CAG-Mal-Th (where Th is a HS-peptide) and no appreciable activity was detected for Pam(3)CAG-Mal, Ol(3)CAG-Mal and Ol(3)CAG-Mal-Th. Our findings indicate that subtle modifications in the peptide moiety of lipopeptides have a great impact on the immunomodulatory properties of these molecules. For the engineering of liposome/lipopeptide-based vaccines, the maleimide derivative of Pam(2)CAG appears to be the best candidate.     

Epiphyseal dysplasia of the femoral head, mild vertebral abnormality, myopia, and sensorineural deafness: report of a pedigree with autosomal dominant inheritance.

A family is presented with short stature, femoral epiphyseal dysplasia, mild vertebral changes, and sensorineural deafness inherited as an autosomal dominant trait. Myopia and retinal detachment presenting in adult life were also present in some affected members. We suggest that this disorder may be a distinct entity within the spondyloepiphyseal dysplasia group of disorders.     

Wilms' tumor in the adult--report of a case and review of the literature

Wilms' tumor is rare in adults. Its histology, grading and staging are identical to those in children. Investigators agree on a combined modality approach in the treatment of adult Wilms' tumor (AWT), but differ on how aggressive it should be. Some advocate adopting the current pediatric protocols which take into account tumor stage and grade. Others recommend using advanced disease regimens for all stages and grades. We report on an 18 year-old male with stage IV favorable histology Wilms' tumor. The patient underwent radical nephrectomy and received postoperative radiotherapy with intensive four-drug chemotherapy. He had one relapse after 12 months which was successfully treated with chemotherapy and radiotherapy. He remains in remission without relapses 36 months after the initial diagnosis. The genetics of Wilms' tumor has been well studied in children but is practically unknown in adults; karyotype and molecular genetic studies in this case were normal.     

Immunoelectron microscopic investigation of surface coat of Wilms tumor cells. Dense lamina is composed of highly sialylated neural cell adhesion molecule

In previous studies we demonstrated the presence of polysialic acid in Wilms tumor by immunohistochemistry and immunoblotting. We now show by immunoelectron microscopy that the cell surface coat of Wilms tumor cells consists of a layer of amorphous material containing polysialic acid but not detectable amounts of laminin, laminin-nidogen complex, or low density proteoglycan. Therefore, Wilms tumor cells are covered by a highly developed and chemically specialized cell surface coat that does not represent a basement membrane, although it bears some structural similarities. Polysialic acid is present on neural cell adhesion molecule that exists in Wilms tumor as two isoforms of approximately 120 and 140 kDa. The cell surface coat exhibits variation in its thickness along the plasma membrane of a single tumor cell, and the variation is inversely related to the extent of cell-cell contact. It is therefore proposed that polysialic acid may modulate the behavior and invasive potential of Wilms tumor cells.     

Interpretation of skeletal muscle four-electrode impedance measurements using spatial and temporal frequency-dependent conductivities

Spatial and temporal frequency-dependent conductivities are used to interpret four-electrode conductivity measurements on skeletal muscle. The model qualitatively explains the observed dependence of the experimental data on the temporal frequency of the injected current, the angle between the electrode array and the fibre direction and the distance between the electrodes.     

The effect of tyrphostin AG-556 on intimal thickening in a mouse model of arterial injury

BACKGROUND: Inflammation has been shown to play an important role in promoting the response to arterial injury and proinflammatory cytokines, such as tumor necrosis factor (TNF) alpha, are candidate mediators. AG-556 is a tyrosine kinase inhibitor proven to be effective in a model of multiple sclerosis-like syndrome in mice due to its immunomodulating effect. In the current study, we investigated the effect of the tyrphostin AG-556 on neointimal thickening and cytokine profile in a model of arterial injury in the mouse. METHODS: Injury was induced by external cuff placement on the left femoral artery of wild-type C57BL/6 mice. AG-556 dissolved in DMSO was injected intraperitoneally daily to the injured mice in a dosage of 2 mg/mouse. Control mice received DMSO injections. Histological analysis was carried out to assess neointimal formation. Splenocytes were cultured in the absence and presence of a mitogen for evaluation of thymidine incorporation and cytokine production. RESULTS: AG-556 treatment significantly attenuated intimal thickening (43,000+/-17,000 microm2; n=11) when compared to DMSO administration (286,000+/-127,000 microm2; n=10; P<0.05). Basal interferon-gamma production by splenocytes from AG-556-treated mice was increased by approximately 20-fold in comparison with levels in DMSO-treated animals, whereas Con-A induced secretion of the cytokine was similar between both groups. Levels of TNF-alpha, IL-4 and IL-10 in the culture supernatant from treated and non-treated animals did not differ significantly. CONCLUSION: The tyrosine kinase inhibitor AG-556 may have a role in the reduction of intimal thickening. The effect could be mediated via an immune modulating effect involving a significant increase in the smooth muscle cell inhibitory cytokine IFN-gamma.     

Target motion measurement without implanted markers and its validation by comparison with manually obtained data

For an effective radiotherapy the exact tumor location must be determined. The localization has to take into account patient's setup position as well as internal organ motion. Among the different localization methods, the use of a computer tomography (CT) scanner in the therapy room has been proposed recently. Achieving a CT with the patient on the therapy couch, a patient's treatment position is captured. We present a method to locate tumor considering internal organ motion and displacements due to respiration. We tested the method with prostate and lung patients. The method found the most probable tumor position as well as, for high-mobility tumors located in the lung, its trajectory during the respiratory cycle. The results of this novel method were validated by comparison with manually determined target position.