Informationen über mögliche Inhibitionsstrategien und Mannosidsynthesen liefert eine Konformationsanalyse der enzymatischen Mannosidhydrolyse. Strukturen in atomarer Auflösung entlang der Reaktionskoordinate machen deutlich, wie eine invertierende α‐Mannosidase ihr Substrat und den Übergangszustand verzerrt. QM/MM‐Rechnungen zeigen die Verformung der Freie‐Energie‐Fläche von isolierter α‐D‐Mannose bei der enzymatischen Umsetzung, für die nur ein konformativer Reaktionsverlauf möglich wird.
We conclude that Actinomyces is involved in the chronic, non-healing inflammatory processes as a characteristic feature of both diseases. Together with the associated presence of increased osteoclast numbers, we suggest that both factors may be involved in osteolytic mechanisms.
Purpose: Human leukocyte antigen (HLA) class I antigen defects, which are frequently present in head and neck squamous cell carcinoma (HNSCC) cells may provide the tumor with an escape mechanism from immune surveillance. Scanty information is available about mechanisms underlying HLA class I antigen defects in both lesions and cell lines from HNSCC. In this study, we investigate the role of antigen processing machinery (APM) component abnormalities in the generation of deficient HLA class I surface expression of HNSCC cells. Experimental Design: Using immunohistochemistry, Western blot, and RT-PCR analyses we correlated the expression of the IFN-g inducible proteasome subunits and of the peptide transporterTAP with that of HLA class I antigens in biopsies and cell lines from primary, recurrent, and metastatic HNSCC. Furthermore, APM component and HLA class I antigen expression in surgically removed lesions were correlated with the course of the disease in order to assess the clinical significance of deficient expression of these molecules. Results: A high frequency of LMP2, LMP7, andTAP1down-regulation or loss was found in tumor lesions and cell lines obtained from HNSCC cancer patients. These defects could be corrected by incubating cells with IFN-g. Furthermore, LMP2, LMP7,TAP1,TAP2, and HLA class I antigen expression rates in primary HNSCC lesions were found to predict overall survival. Lastly, the level of LMP7 expression was significantly associated with disease recurrence at 2 years. Conclusions: Our results suggest that the analysis of APM component expression in HNSCC lesions can provide useful prognostic information in patients with HNSCC.
These clinical results provide evidence that immediate implant placement might improve the facial soft tissue level. This was more evident in cases with a greater recession and an additional treatment with connective tissue grafts.
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