Zur klinik der greisenappendicitis

Zusammenfassung In der nicht selten geradezu unwahrscheinlich mangelhaften Reaktionskraft des Greisenorganismus-selbst auf Sch?digungen schwerster Artist die gro?e Gefahr für die Verkennung einer im Greisenalter auftretenden Appendicitis begründet. Gerade bei der Appendicitis ist diese Gefahr insofern besonders gro?, als es sich hier um ein im all-gemeinen besonders gut bekanntes Krankheitsbild handelt, von dessen wohlgekennzeichneter Symptomatologie Abweichungen in dieser krassen Form schlechthin für unm?glich gehalten werden. Dem an 2 Beispielen aus der Praxis verdeutlichten Gefahrenmoment mu? bei der Diagnostik automatisch und an erster Stelle hinreichend Rechnung getragen werden.      

Investigation into the prevalent CRISPR–Cas systems among the Aeromonas genus

Clustered regularly interspaced short palindromic repeats (CRISPR) is a prokaryotic adaptive immune system that checks invasion by mobile genetic elements through nuclease targeting. In this study, we investigated the occurrence, diversity, and features of the CRISPR system in the genus Aeromonas using bioinformatics tools. Only 13 out of 122 complete genomes (10.66%) of the genus Aeromonas from the NCBI GenBank database harbored the CRISPR system. The Type I–F system was the most prevalent CRISPR system among the Aeromonads, followed by the Type I–E system. Only one strain harbored a Type I–C CRISPR system. Among the Aeromonads, Aeromonas caviae (22.7%) and Aeromonas veronii (20%) had a higher prevalence rate of the complete CRISPR system. The analysis of direct repeat (DR) sequences showed that all could form stable RNA secondary structures. A phylogenetic tree generated for the Cas1 protein classified CRISPR subtypes into three distinct clusters. Among the 748 spacers investigated, 41.98% and 17.25% showed perfect homology to phage and plasmid sequences, respectively. Some arrays had duplicated spacers. The CRISPR loci are closely linked to antibiotic resistance genes in most strains. Collectively, our results would contribute to research on antibiotic resistance in the Aeromonas group, and provide new insights into the diversity and evolution of the CRISPR–Cas system.     

Ueber den centralen Ursprung des Hirnschenkelfusses beim Kaninchen

Ohne Zusammenfassung     

Ueber ein bisher noch selten beobachtetes Markbündel an der Basis des menschlichen Gehirns

Ohne Zusammenfassung     

Sperm protein 17 (Sp17) is a suitable target for immunotherapy of multiple myeloma

Sperm protein 17 (Sp17) is a protein recently identified as a novel cancer-testis (CT) antigen in multiple myeloma (MM). Because this tumor antigen demonstrates a very restricted normal tissue expression, Sp17 may be an excellent target for tumor vaccine of MM. In this study, we determined the ability to generate Sp17-specific HLA class I-restricted cytotoxic T lymphocytes (CTLs) from the peripheral blood of 4 patients with MM, 3 consecutive Sp17(+) patients, and 1 Sp17(-) patient. Dendritic cells were generated from monocytes of 4 patients with MM and used to present a recombinant Sp17 protein to autologous T cells. Following 4 rounds of antigen stimulation, the CTLs were tested for their ability to kill autologous targets in an Sp17-dependent and HLA-class I- restricted manner in standard cytotoxicity assays. Despite previous chemotherapy and the immunosuppression so often associated with MM, CTL generation was successful in all 4 patients, irrespective of the Sp17 status of their tumors. Most importantly, the CTLs were able to lyse autologous tumor cells that expressed Sp17. Tumor cell lysis in all cases appeared to be mainly mediated by perforin and could be blocked by concanamycin A. We conclude that Sp17 is a suitable target for immunotherapy of MM. Our findings provide the basis for a clinical study aimed at inducing a cellular immune response directed at Sp17(+) MM.     

Metabotropic glutamate receptor 5 positive allosteric modulators are neuroprotective in a mouse model of Huntington's disease

Background and Purpose

Huntington''s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. We have previously demonstrated that the cell signalling of the metabotropic glutamate receptor 5 (mGluR5) is altered in a mouse model of HD. Although mGluR5-dependent protective pathways are more activated in HD neurons, intracellular Ca²⁺ release is also more pronounced, which could contribute to excitotoxicity. In the present study, we aim to investigate whether mGluR5 positive allosteric modulators (PAMs) could activate protective pathways without triggering high levels of Ca²⁺ release and be neuroprotective in HD.

Experimental Approach

We performed a neuronal cell death assay to determine which drugs are neuroprotective, Western blot and Ca²⁺ release experiments to investigate the molecular mechanisms involved in this neuroprotection, and object recognition task to determine whether the tested drugs could ameliorate HD memory deficit.

Key Results

We find that mGluR5 PAMs can protect striatal neurons from the excitotoxic neuronal cell death promoted by elevated concentrations of glutamate and NMDA. mGluR5 PAMs are capable of activating Akt without triggering increased intracellular Ca²⁺ concentration ([Ca²⁺]_i); and Akt blockage leads to loss of PAM-mediated neuroprotection. Importantly, PAMs'' potential as drugs that may be used to treat neurodegenerative diseases is highlighted by the neuroprotection exerted by mGluR5 PAMs on striatal neurons from a mouse model of HD, BACHD. Moreover, mGluR5 PAMs can activate neuroprotective pathways more robustly in BACHD mice and ameliorate HD memory deficit.

Conclusions and Implications

mGluR5 PAMs are potential drugs that may be used to treat neurodegenerative diseases, especially HD.