Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas.

Platelet-derived growth factor (PDGF) receptor signaling has been implicated in the development of glial tumors, but not yet been examined in choroid plexus carcinomas, pediatric tumors with dismal prognosis for which novel treatment options would be desirable. Therefore, protein expression of PDGF receptors alpha and beta as well as amplification status of the respective genes, PDGFRA and PDGFRB, were examined in a series of 22 patients harboring choroid plexus carcinoma using immunohistochemistry and chromogenic in situ hybridization (CISH). The majority of choroid plexus carcinomas expressed PDGF receptors with 6 cases (27%) displaying high staining scores for PDGF receptor alpha and 13 cases (59%) showing high staining scores for PDGF receptor beta. Correspondingly, copy-number gains of PDGFRA were observed in 8 cases out of 12 cases available for CISH and 1 case displayed amplification (six or more signals per nucleus). The proportion of choroid plexus carcinomas with amplification of PDGFRB was even higher (5/12 cases). PDGFRB amplification status and PDGF receptor beta protein expression scores were significantly correlated (P=0.01, Spearman). Expression status of PDGF receptor alpha or PDGF receptor beta was not significantly associated with progression-free survival. To conclude, expression and amplification of PDGF receptors, particularly PDGF receptor beta, are frequent in choroid plexus carcinomas, providing a first rationale for the development of treatments targeting PDGF receptor signaling in these rare malignant pediatric tumors.     

Der klinische Wert quantitativ-immunochemischer Bestimmungen verschiedener Proteine im Liquor cerebrospinalis

Zusammenfassung Es wird ein klinischer Erfahrungsbericht mit der quantitativ-immunochemischen Bestimmung verschiedener Liquorproteine vorgelegt. Untersucht wurde der Liquor bei 213 Krankheitsfällen und gearbeitet mit der radialen Immundiffusionsmethode nach Mancini et al. In sämtlichen Fällen wurden neben den üblichen Liquoruntersuchungen _G-Globulin, saures ₁-Glykoprotein, Haptoglobin und unter den liquorfremden Proteinen das _M-Globulin und das-Lipoprotein quantitativ bestimmt. Die wesentliche Bereicherung der klinischen Liquordiagnostik durch die aufgeführten Untersuchungen wird gesehen in der Erfassung der jeweiligen immunologischen Reaktionslage und einer genaueren Bestimmung der Permeabilitätsintensität bei Hirnschrankenstörungen. Ferner kann gelegentlich quantitativen Liquorproteinbestimmungen der Hinweis auf akute Krankheitsphasen, ausgedehnte Gewebsdestruktionen und auf abgelaufene Blutungen in die Liquorräume entnommen werden. Dem Nachweis des-Lipoprotein im Liquor sowie vielleicht auch der Höhe des _G-Globulingehaltes kommt schließlich ein klinisch-diagnostischer Wert bei Raumforderungen im ZNS-Bereich zu.

---

Summary This paper presents a clinical experience with the quantitative immuno-chemical analysis of different cerebrospinal fluid proteins. The CSF of 213 patients suffering from a CNS disease was examined. We used the radial immun diffusion method as described by Manciniet al. Besides the usual CSF examinations, _G-Globulin, acid ₁-Glycoprotein, and Haptoglobin were quantitatively determined in all cases. Of those proteins that under healthy conditions do not occur in the CSF the _M-Globulin and the-Lipoprotein were quantitatively evaluated, too. The essential additional value of the clinical CSF diagnostic procedures derived from those examinations is seen in the comprehension of the respective immunological reaction state as well as of a more exact evaluation of the permeability intensity in brain barrier system disturbances. Furthermore, quantitative CSF determinations can occasionally point to acute episodes of a CNS disease, an extensive tissue destruction, or to a CSF dysproteinosis following a bleeding into the CSF space. The proof of the existence of-Lipoprotein in the CSF, and perhaps also the level of the _G-Globulin, finally show a clinical-diagnostic significance in cases of space occupying lesions within the CNS.

     

Über das Prodigiosin,den roten Farbstoff des Bacillus prodigiosus

Ohne Zusammenfassung     

Decentred comparative research: Context sensitive analysis of maternal health care

Cross-national comparison is an important tool for health care research, but too often those who use this method fail to consider important inter-national differences in the social organisation of health care and in the relationship between health care practices and social experience. In this article we make the case for a context-sensitive and reflexive analysis of health care that allows researchers to understand the important ways that health care systems and practices are situated in time and place. Our approach--decentred comparative research--addresses the often unacknowledged ethnocentrism of traditional comparative research. Decentred cross-national research is a method that draws on the socially situated and distributed expertise of an international research team to develop key concepts and research questions. We used the decentred method to fashion a multilevel framework that used the meso level of organisation (i.e., health care organisations, professional groups and other concrete organisations) as an analytical starting point in our international study of maternity care in eight countries. Our method departs from traditional comparative health systems research that is most often conducted at the macro level. Our approach will help researchers develop new and socially robust knowledge about health care.     

Hoher Impact – am besten im Original

Notfall + Rettungsmedizin -     

Infektiologie und Hygiene bei Notfallpatienten

Notfall + Rettungsmedizin -     

Intracellular depletion of insulin: a comparative study with palmitate,oleate and elaidate in INS-1 cells

OBJECTIVE: Free fatty acids (FFAs) deplete the intracellular insulin stores of pancreatic beta-cells. It has been suggested that this results from a lipotoxic dysregulation of both insulin secretion and insulin synthesis. In the present study, this hypothesis was tested within a 12-h time-course by directly relating the FFA-induced loss of intracellular insulin to corresponding parameters of insulin secretion and de novo biosynthesis. Palmitate, cis-monoenic oleate and the trans-monoenic elaidate were employed as model FFAs to elucidate potentially different effects due to chain length and configuration. METHODS: INS-1 cells were incubated for 1, 4 or 12 h with 11.2 mmol/l glucose with 200 micromol/l palmitate, oleate or elaidate and compared with non-FFA-exposed controls with respect to content and secretion of immunoreactive insulin (IRI). Biosynthesis of insulin was monitored by pulse-labeling experiments and by Northern blot analysis. RESULTS: IRI content dropped by 50-60% after a short-term exposure with all FFAs employed (P< or =0.001). It tended to recover after 12 h of treatment with oleate and elaidate but not with palmitate. FFA treatment increased insulin secretion by 25% (P< or =0.05) which could not account quantitatively for the intracellular loss. FFA-induced changes in insulin biosynthesis did not correlate clearly with the FFA-induced intracellular loss. CONCLUSIONS: The FFA-induced loss of IRI is an acute effect independent of the FFA employed. It cannot be sufficiently explained by FFA-induced perturbances of IRI secretion and biosynthesis. We therefore postulate an additional FFA-triggered mechanism, e.g. intracellular IRI degradation.     

Non-invasive tumor decoding and phenotyping of cerebral gliomas utilizing multiparametric 18F-FET PET-MRI and MR Fingerprinting

European Journal of Nuclear Medicine and Molecular Imaging - The introduction of the 2016 WHO classification of CNS tumors has made the combined molecular and histopathological characterization of...