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Biomedical subjects

Sebastian Manegold

Publications and source records attributed to Sebastian Manegold.

2 recordsLinked to original sources

Peripheral talar fractures.

Peripheral fractures of the talus are uncommon and often overlooked. CT scanning has become the imaging modality of choice and is necessary for decision making on treatment. Displaced peripheral fractures have to be managed with open reduction and internal fixation. Precise anatomical reduction is necessary to achieve a good result. A rigid internal fixation with interfragmentary lag screws is the method of choice in almost all fractures, which allows early postoperative mobilization. The outcome is related to the degree of the chondral lesion and the degree of instability of the subtalar joint, but it may be poor due to the treatment. Early diagnosis and proper treatment achieve the best possible results and prevent long-term complications. Typical complications of the fracture are nonunion and malalignment with slight subtalar instability or osseous overgrowth with secondary impingement and posttraumatic subtalar arthritis.

Arthroscopy↗

Adenoviral vectors with E1A regulated by tumor-specific promoters are selectively cytolytic for breast cancer and melanoma.

We have previously demonstrated that a truncated form of the L-plastin promoter can confer tumor-specific patterns of expression on replication-incompetent adenoviral vector reporter and therapeutic transcription units. In this report, a 2.5-kb truncated version of the L-plastin promoter was placed 5' to the E1A gene of a wild-type adenovirus. The vector generated (Ad-Lp-E1A) was directly cytotoxic to established breast and ovarian cancer cell lines and to primary explant cultures derived from ovarian cancer, but was not cytotoxic to explant cultures of normal mammary epithelial cells. This vector was not cytotoxic to cell lines in which the L-plastin E1A transcription unit was not expressed, whereas the same cell lines were sensitive to the cytotoxic effect of a replication-competent adenoviral vector in which the cytomegalovirus (CMV) promoter drove E1A expression. When the tyrosinase promoter/enhancer was placed 5' to the E1A gene in the adenoviral backbone, the resulting vector (Ad-Tyr-E1A) was selectively toxic to melanoma cells and one percent as toxic to explants of ovarian cancer cells as the Ad-Lp-E1A vector. Injection of these vectors (Ad-Lp-E1A and Ad-Tyr-E1A) into nodules derived from the MCF-7 and MDA-MB-468 human breast cancer cell lines and the TF-2 human melanoma cell line, respectively, which were growing subcutaneously in severe combined immunodeficiency (SCID) mice, induced regression of these tumors. Such vectors may therefore be useful in cancer treatment.

Adenoviridae↗