Incorporation of dUMP into DNA is a major source of spontaneous DNA damage, while excision of uracil is not required for cytotoxicity of fluoropyrimidines in mouse embryonic fibroblasts

Uracil may arise in DNA as a result of deamination of cytosine or through incorporation of dUMP instead of dTMP during replication. We have studied the steady-state levels of uracil in the DNA of primary cells and mouse embryonic fibroblast (MEF) cell lines from mice deficient in the Ung uracil-DNA glycosylase. The results show that the levels of uracil in the DNA of Ung(-/-) cells strongly depend on proliferation, indicating that the uracil residues originate predominantly from misincorporation during replication. Treatment with 5-fluoro-2'-deoxyuridine (5-FdUrd) or 5-fluorouracil (5-FU) gives rise to a dose-dependent increase of uracil in Ung(-/-) MEFs (up to 1.5-fold) but not in wild-type cells. Interestingly, Ung(-/-) MEFs accumulate AP-sites as well as uracil in response to 5-FdUrd but not to 5-FU. This accumulation of repair intermediates suggests a loss of tightly co-ordinated repair in the absence of Ung, and correlates with stronger inhibition of cell proliferation in response to 5-FdUrd, but not to 5-FU, in Ung(-/-) MEFs compared with wild-type cells. However, other cytotoxic effects of these fluoropyrimidines are comparable in both wild-type and Ung-deficient cells, demonstrating that excision of uracil from DNA by the Ung uracil-DNA glycosylase is not a prerequisite for obtaining cytotoxicity.     

Actinonin induces apoptosis in U937 leukemia cells

S100A4 has multiple functions in cell cycle progression and cell motility, and has been implicated in cancer invasion. In this study, we examined the expression of S100A4, E-cadherin and its related proteins in oral squamous cell carcinoma (SCC) cell lines with different invasive phenotypes, grade 4C and 4D. Furthermore, grade 4C OSC-19 cells expressing E-cadherin were transfected with S100A4-expression vector and the expression of E-cadherin-related proteins in the stable clone was examined to elucidate the relationship between S100A4 and E-cadherin. Constitutive over-expression of S100A4 in stable transformant of OSC-19 (OSC-19/S100A4) cells led to down-regulation of E-cadherin and β-catenin. Furthermore, grade 4D invasive cell lines (HOC313 and TSU) expressing S100A4 mRNA did not express E-cadherin, P-cadherin, and β-catenin, while γ-catenin protein was only weakly expressed. Thus, the mRNA expression of E-cadherin was reversely correlated with S100A4 expression in oral SCCs. Interestingly, vascular endothelial growth factor-C was up-regulated in OSC-19/S100A4 cells. In summary, S100A4-mediated regulation of E-cadherin expression may play an important mechanism in invasion and metastasis of oral SCC.     

Alteration of argon laser–induced scars by the pulsed dye laser

Ten patients with portwine stains (PWS) with test sites previously exposed to an argon laser were evaluated and subsequently treated with five pulsed dye (585 nm) laser treatments over a 10 month period. Clinical assessments, skin surface texture analyses using optical profilometry, and light microscopic histological evaluations were performed prior to commencement and at the end of the study in all ten patients. A change in the skin texture with return of skin markings approximating those of normal skin measured by optical profilometry was observed in the argon treated PWS skin following pulsed dye laser treatments. © 1993 Wiley-Liss, Inc.     

Clinical course of porokeratosis ptychotropica over 7 years in an otherwise healthy child

Porokeratosis ptychotropica is an unusual variant of porokeratosis characterized by papules and plaques located on the buttocks and gluteal cleft and showing multiple coronoid lamellae on histology. In this case report, we present the longitudinal clinical course of porokeratosis ptychotropica in a pediatric patient with individual red-brown hyperkeratotic lesions that enlarged and became confluent prior to surgical intervention. We also discuss the etiology of porokeratosis ptychotropica and review current as well as future treatment options for the disease.     

Improved outcome by identification of high-risk nonocclusive mesenteric ischemia, aggressive reexploration, and delayed anastomosis

: The factors associated with outcome of patients with nonocclusive mesenteric ischemia are poorly defined. : Over a 7-year period, 34 consecutive patients with nonocclusive mesenteric ischemia were identified. : The mean age of the study patients was 63 years (range 31 to 94); 21 of 34 (62%) were men. The mean delay in diagnosis was 31 hours (range 7 hours to 6 days). Seven of 34 (21%) underwent preoperative visceral arteriography. Two of these 7 required surgery, and both died as a result of intestinal infarction. The remaining 27 had the diagnosis made at celiotomy. Among the 29 who were explored, 16 of 29 (55%) had intestinal infarction. Twenty-one of 29 (72%) had segmental bowel injury whereas 8 of 29 (28%) had massive injury. Among those with segmental infarction, primary anastomosis was performed in 12 of 21 patients (57%); 5 of the 12 (42%) died. Nine of 21 patients (43%) underwent delayed anastomosis; 2 of the 9 (22%) died. No patient with massive injury underwent primary anastomosis. Second-look laparotomy was performed on 22 of 29 (76%). Eleven of those 22 (50%) had a further bowel resection. Overall, 16 of 29 (55%) who underwent surgery for nonocclusive mesenteric ischemia are alive. : Improved survival from nonocclusive mesenteric ischemia is dependent upon the identification of high-risk groups, aggressive reexploration, and delayed intestinal anastomosis.