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K Søe

Publications and source records attributed to K Søe.

3 recordsLinked to original sources

Cellular stress triggers the human topoisomerase I damage response independently of DNA damage in a p53 controlled manner.

The 'human topoisomerase I (htopoI) damage response' was reported to be triggered by various kinds of DNA lesions. Also, a high and persistent level of htopoI cleavage complexes correlated with apoptosis. In the present study, we demonstrate that DNA damage-independent induction of cell death using colcemid and tumor necrosis factor alpha is also accompanied by a strong htopoI response that correlates with the onset of apoptotic hallmarks. Consequently, these results suggest that htopoI cleavage complex formation may be caused by signaling pathways independent of the kind of cellular stress. Thus, protein interactions or signaling cascades induced by DNA damage or cellular stress might lead to the formation of stabilized cleavage complexes rather than the DNA lesion itself. Finally, we show that p53 not only plays a key role in the regulation of the htopoI response to UV-C irradiation but also to treatment with colcemid.

Blotting, Western↗

A human topoisomerase I cleavage complex is recognized by an additional human topisomerase I molecule in vitro.

Several recent studies have shown that human topoisomerase I (htopoI) can recognize various DNA lesions and thereby form a covalent topoisomerase I-DNA complex, which is known to be detrimental to cells. We have investigated whether htopoI recognizes another htopoI that is covalently trapped on a DNA substrate. For this purpose we created an artificial DNA substrate containing a specific topoisomerase I binding sequence, where the enzyme was trapped in the covalently bound form. We demonstrate that, in vitro, free htopoI stimulates the formation of an additional cleavage complex immediately upstream of the covalently bound topoisomerase I. The predominant distance between the two cleavage sites is 13 nt. In addition we find that these two enzymes may form direct protein-protein contacts and we propose that these may be mediated through the formation of a dimer by domain swapping involving the C-terminal and the core domains. Finally, we discuss the possibility that the double cleavage reaction may be the initial step for the removal of the recognized cleavage complex.

Animals↗

Intestinal obstruction after appendectomy.

BACKGROUND: The frequency of intestinal obstruction varies in the literature (0.2-10.7%) and requires evaluation in a proper design. METHODS: From 1978 to 1985, 1951 patients underwent appendectomy; 58 patients were excluded because of appendectomy per occasionem, 156 because of previous laparotomy, and 190 because of simultaneous major surgery. Three foreigners were lost to follow-up. The cohort was linked to the Danish National Inpatient Register for identification of cases, defined by intestinal obstruction requiring surgical intervention. RESULTS: The follow-up period was long (median, 3563 days; range, 2-5113). Twenty-one patients developed intestinal obstruction. The cumulated incidence was 0.33% after 30 days, 0.79% after 1 year, and 1.51% after 14 years. Female sex as compared with male sex (RR = 3.91; 95% confidence limits (CL), 1.25-12.0) and removal of a removal of a normal appendix as compared with an inflamed appendix (RR = 4.0; 95% CL, 1.28-12.5) carried a significantly higher risk of intestinal obstruction. CONCLUSION: Intestinal obstruction after open appendectomy is rare.

Adolescent↗