APRIL, a New Ligand of the Tumor Necrosis Factor Family, Stimulates Tumor Cell Growth

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family designated APRIL (for a proliferation-inducing ligand). Although transcripts of APRIL are of low abundance in normal tissues, high levels of mRNA are detected in transformed cell lines, and in human cancers of colon, thyroid, and lymphoid tissues in vivo. The addition of recombinant APRIL to various tumor cells stimulates their proliferation. Moreover, APRIL-transfected NIH-3T3 cells show an increased rate of tumor growth in nude mice compared with the parental cell line. These findings suggest that APRIL may be implicated in the regulation of tumor cell growth

The diagnostic value of Gb3-skin deposits in Patients with Fabry Disease

In der vorliegenden Arbeit wurde geprüft, ob Gb3 in Hautstanzbiopsien von Patienten mit M. Fabry nachweisbar ist, die Ablagerungen quantifizierbar sind, mit der Krankheitsschwere korrelieren, und ob eine Unterscheidung von Patienten und gesunden Kontrollen anhand der dermalen Gb3-Ablagerungen möglich ist. Es wurden 84 Patienten mit M. Fabry über das FAZiT sowie 27 gesunde Kontrollen zwischen 2008 und 2013 prospektiv rekrutiert und jeweils eine proximale und eine distale Hautbiopsie entnommen. Zusätzlich erfolgten eine Anamnese, eine klinische Untersuchung, eine QST, das Ausfüllen von Fragebögen mit der Fragestellung nach Schmerz und Depression sowie eine Blutentnahme und kardiale Diagnostik. Die Immunfluoreszenz erfolgte mit Antikörpern gegen CD77, einem Marker für Gb3. Es erfolgte die verblindete, semiautomatische Quantifizierung der Gb3 Ablagerungen. Hierzu wurden pro Biopsie drei ROI ausgewählt und die Fläche der ROIs mit Gb3-Ablagerungen in Relation zu der Gesamtfläche der ROIs gesetzt. Für die Auswertung wurden die Patienten sowohl nach Geschlecht als auch nach Krankheitsschwere und einzelnen Symptomen stratifiziert Die Gb3 Ablagerungen ließen sich bevorzugt in Schweißdrüsen und Endothel nachweisen. Es fanden sich jedoch auch größere Mengen an Gb3-Ablagerungen ohne ersichtliches anatomischer Korrelat. Die Gb3-Ablagerungen wurden semiautomatisch quantifiziert. Es konnte nachgewiesen werden, dass männliche Fabry-Patienten eine deutlich größere Menge an Gb3 in den distalen Hautbiopsien zeigen als gesunde Kontrollen, Patienten mit einer eingeschränkten Nierenfunktion hatten eine größere Menge an Gb3-Ablagerungen in der Haut als Patienten mit einer uneingeschränkten Nierenfunktion. Bei Patienten mit einer SFN waren erhöhte dermale Gb3 Mengen vorhanden im Vergleich zu gesunden Kontrollen, bei Patienten ohne eine SFN fand sich dieser Unterschied nicht. Patienten mit einem niedrigen SNAP zeigten im Vergleich zu gesunden Kontrollen eine größere Menge an Gb3 in ihrer distalen Haut, bei Patienten mit einem höheren SNAP fand sich dies nicht. Aus diesen Ergebnissen ergeben sich ein mögliches weiteres Werkzeug sowohl für die Diagnosestellung als auch für das Monitoring der Erkrankung, sowie weiterführend auch ein möglicher Indikator für den Therapieerfolg der ERT.Fabry disease (FD) is an X-chromosomally linked disease which leads to deposits of globotriaosylceramide 3 (Gb3) in several tissues. The aim of this study was to prove, that these deposits can be shown in the skin of patients with FD via immunofluorescence, that Gb3 deposits can be quantified, that patients with FD have more Gb3-deposits in their skin than healthy controls and that the amount of Gb3 deposits in skin correlates with disease severity. 84 patients were prospectively recruited in the Würzburg Fabry Center for Interdisciplinary Therapy as well as 27 healthy controls. Every patient received a skin biopsy from a proximal and a distal location, a physical examination as well as a thorough anamnesis, filled out questionnaires regarding pain and symptoms hinting for depression and underwent cardiac diagnostics. Immunofluorescence double stains were done for Gb3 and protein-gene-product 9.5 as well as for Gb3 and von Willebrand factor. We quantified the amount of Gb3 semi-automatically in three predetermined regions of interest. We could show, that Gb3 can be visualized and quantified in the skin of patients with FD using immunofluorescence. Furthermore, male patients with FD had a higher Gb3 load in their distal skin than healthy controls (p<0.05). Male patients with FD and an impaired renal function had a higher Gb3 load in their distal skin (p<0.05). Similarly, it was shown, that male patients with a small fiber neuropathy had a higher load of Gb3 in their distal skin than male patients without a small-fiber neuropathy (p<0.05). In conclusion it can be stated, that the quantification of Gb3 via immunofluorescence could be used in the diagnostics of FD and might be of value as a biomarker in the course of the disease

Anti-glycin-receptor antibody related stiff-person syndrome under treatment with an immune checkpoint inhibitor

Purpose!#!To determine the anatomical and functional outcomes of an extended 6-month intravitreal anti-vascular endothelial growth factor (anti-VEGF) upload in choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSCR).!##!Methods!#!A retrospective database analysis was performed applying the following inclusion criteria: (1) diagnosis of CSCR, (2) diagnosis of secondary CNV, and (3) treatment of at least six consecutive injections of anti-VEGF. Outcome measures included the change of central retinal subfield thickness, remodeling of the pigment epithelium detachments, and change in visual function.!##!Results!#!Twenty-one eyes of 21 patients were included. Mean patient age was 65 ± 8.3 years, and 35% of the patients (n = 8) were female. Mean disease duration before diagnosis of CNV was 48 ± 25.3 months. Mean central retinal thickness decreased from 346 ± 61 to 257 ± 57 μm (p &amp;lt; 0.01) after the sixth injection while mean visual acuity improved from 0.65 ± 0.35 to 0.49 ± 0.29 (logMAR; p &amp;lt; 0.01). Of note, an extended upload of six as opposed to three injections yielded an additional mean central retinal thickness reduction (280 ± 46 μm vs. 257 ± 57 μm, p = 0.038). Significant CNV remodeling was observed as a decrease in pigment epithelium detachment (PED) vertical (p = 0.021) and horizontal diameter (p = 0.024) as well as PED height (p &amp;lt; 0.01).!##!Conclusion!#!An extended anti-VEGF upload of six consecutive injections seems to be effective in inducing CNV remodeling and fluid resorption in CNV complicating chronic CSCR

German Language Adaptation of the NAVS (NAVS-G) and of the NAT (NAT-G): Testing Grammar in Aphasia

Grammar provides the framework for understanding and producing language. In aphasia, an acquired language disorder, grammatical deficits are diversified and widespread. However, the few assessments for testing grammar in the German language do not consider current linguistic, psycholinguistic, and functional imaging data, which have been shown to be crucial for effective treatment. This study developed German language versions of the Northwestern Assessment of Verbs and Sentences (NAVS-G) and the Northwestern Anagram Test (NAT-G) to examine comprehension and production of verbs, controlling for the number and optionality of verb arguments, and sentences with increasing syntactic complexity. The NAVS-G and NAT-G were tested in 27 healthy participants, 15 right hemispheric stroke patients without aphasia, and 15 stroke patients with mild to residual aphasia. Participants without aphasia showed near-perfect performance, with the exception of (object) relative sentences, where accuracy was associated with educational level. In each patient with aphasia, deficits in more than one subtest were observed. The within and between population-groups logistic mixed regression analyses identified significant impairments in processing syntactic complexity at the verb and sentence levels. These findings indicate that the NAVS-G and NAT-G have potential for testing grammatical competence in (German) stroke patients

Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy

[$^{18}$F]fluorodeoxyglucose (FDG) PET and [$^{123}$I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 +/- 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson's disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator #1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater #1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred