Neuronal precursor cells with dopaminergic commitment in the rostral migratory stream of the mouse

Neuroblasts born in the subventricular zone of adult mammals migrate via the rostral migratory stream into the granular cell layer or periglomerular layer of the olfactory bulb to differentiate into interneurons. To analyze if new neurons in the granular cell layer or periglomerular layer have different origins, we inserted a physical barrier into the rostral migratory stream, depleted cell proliferation with cytarabine infusions, labeled newborn cells with bromodeoxyuridine, and sacrificed mice after short-term (0, 2, or 14 days) or long-term (55 or 105 days) intervals. After short-term survival, the subventricular zone and rostral migratory stream rapidly repopulated with bromodeoxyuridine(+) cells after cytarabine-induced depletion. Nestin, glial fibrillary acidic protein and the PAX6 were expressed in bromodeoxyuridine(+) cells within the rostral migratory stream downstream of the physical barrier. After long-term survival after physical barrier implantation, bromodeoxyuridine(+) neurons were significantly reduced in the granular cell layer, but bromodeoxyuridine(+) and dopaminergic neurons in the periglomerular layer remained unaffected by the physical barrier. Thus, newborn neurons for the granular cell layer are mainly recruited from neural stem cells located in the subventricular zone, but new neurons for the periglomerular layer with dopaminergic predisposition can rise as well from neuronal stem or precursor cells in the rostral migratory stream

Antibodies against citrullinated proteins of IgA isotype are associated with progression to rheumatoid arthritis in individuals at-risk

ObjectiveEvents triggering disease outbreak in individuals at-risk for rheumatoid arthritis (RA at-risk) remain unclear, and the role of the various anticitrullinated protein antibody (ACPA) isotypes in this process is still to be established. We aimed to investigate the prevalence of IgA ACPA in RA at-risk individuals, their role in the transition from the RA at-risk status to RA and their dynamics during this transition.MethodsCross-sectional measurement of serum IgA1 and IgA2 ACPA levels was conducted in healthy controls, RA at-risk individuals and patients with RA and compared with the frequency of RA development in at risk individuals during a follow-up of 14 months. In addition, longitudinal measurements of serum IgA1 and IgA2 ACPA levels prior to, at and after the onset of RA were performed.ResultsApproximately two-thirds of RA at-risk individuals were positive for serum IgA1 and IgA2 ACPA in levels comparable to IgG ACPA positive patients with RA. IgA1, but not IgA2 ACPA positivity was associated with the transition from the RA at-risk state to RA within the following 14 months. Interestingly, during this transition process, IgA1 ACPA levels declined at RA onset and also thereafter during the early phase of RA. This decline was confirmed in a second, independent cohort.ConclusionBoth IgA1 and IgA2 ACPA are present in RA at-risk individuals, but only IgA1 ACPA are associated with the progression to RA. The observed decline in serum IgA1 ACPA levels before the onset of RA might indicate starting barrier leakiness prior to disease outbreak

Waldecks Weg ins Dritte Reich Untersuchung der gesellschaftlichen und politischen Strukturen eines laendlichen Raumes waehrend der Weimarer Republik und zu Beginn des Dritten Reiches

SIGLEFES Bonn(Bo133)-C86-301 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Waldecks Weg ins Dritte Reich Untersuchung der gesellschaftlichen und politischen Strukturen eines laendlichen Raumes waehrend der Weimarer Republik und zu Beginn des Dritten Reiches

SIGLEFES Bonn(Bo133)-C86-301 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Waldecks Weg ins Dritte Reich gesellschaftliche und politische Strukturen eines laendlichen Raumes waehrend der Weimarer Republik und zu Beginn des Drittes Reiches

FES Bonn(Bo133)-A88-5991 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEals Ms. gedr.DEGerman

Wissenschaft und Gesellschaft

UuStB Koeln(38)-910106579 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEManuskriptdr.DEGerman

Characterization of the Inducible and Slow-Releasing Hydrogen Sulfide and Persulfide Donor P*: Insights into Hydrogen Sulfide Signaling

Hydrogen sulfide (H2S) is an important mediator of inflammatory processes. However, controversial findings also exist, and its underlying molecular mechanisms are largely unknown. Recently, the byproducts of H2S, per-/polysulfides, emerged as biological mediators themselves, highlighting the complex chemistry of H2S. In this study, we characterized the biological effects of P*, a slow-releasing H2S and persulfide donor. To differentiate between H2S and polysulfide-derived effects, we decomposed P* into polysulfides. P* was further compared to the commonly used fast-releasing H2S donor sodium hydrogen sulfide (NaHS). The effects on oxidative stress and interleukin-6 (IL-6) expression were assessed in ATDC5 cells using superoxide measurement, qPCR, ELISA, and Western blotting. The findings on IL-6 expression were corroborated in primary chondrocytes from osteoarthritis patients. In ATDC5 cells, P* not only induced the expression of the antioxidant enzyme heme oxygenase-1 via per-/polysulfides, but also induced activation of Akt and p38 MAPK. NaHS and P* significantly impaired menadione-induced superoxide production. P* reduced IL-6 levels in both ATDC5 cells and primary chondrocytes dependent on H2S release. Taken together, P* provides a valuable research tool for the investigation of H2S and per-/polysulfide signaling. These data demonstrate the importance of not only H2S, but also per-/polysulfides as bioactive signaling molecules with potent anti-inflammatory and, in particular, antioxidant properties

Adverse events and efficacy of TNF-alpha blockade with infliximab in patients with systemic lupus erythematosus : long-term follow-up of 13 patients.

OBJECTIVE: To follow-up on all available infliximab-treated SLE patients for safety and long-term efficacy in order to extract information that is useful for planning appropriate controlled trials with infliximab in SLE. METHODS: We analysed charts of six patients treated in an open-label safety trial and seven additional patients treated with infliximab on a compassionate care basis for uncontrolled SLE organ inflammation. RESULTS: Out of nine patients with lupus nephritis, six had a long-term response after four infusions of infliximab in combination with AZA, lasting for up to 5 years. All five patients with lupus arthritis responded, but this response did not last for >2 months after the last infusion. One additional patient had a long-lasting improvement in SLE interstitial lung disease. No symptoms suggestive of infliximab-induced SLE flares occurred in any patients. Short-term treatment appeared relatively safe, but one patient developed deep-vein thrombosis and several infections. Under long-term therapy, two patients had life-threatening or fatal events, namely CNS lymphoma and Legionella pneumonia. Retreatment and treatment without concomitant immunosuppression led to drug reactions. CONCLUSIONS: Short-term therapy with four infusions of infliximab in combination with AZA was relatively safe, and had remarkable long-term efficacy for lupus nephritis and, potentially, also interstitial lung disease. Long-term therapy with infliximab, however, was associated with severe adverse events in two out of three SLE patients, which may have been provoked by infliximab and/or by their long-standing refractory SLE and previous therapie