Bacterial and mammalian DNA alkyltransferases sensitize Escherichia coli to the lethal and mutagenic effects of dibromoalkanes

Here we confirm and extend our previous studies demonstrating that the mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is markedly enhanced (not prevented) in bacteria expressing the O6- alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli ogt gene. We demonstrate that, in close parallel with mutagenesis, the Ogt ATase sensitizes the bacteria to the lethal effects of these carcinogens, suggesting that one or more of the potentially mutagenic lesions induced by DBE and DBM in the presence of Ogt has additional lethal capacity. We further demonstrate that the sensitization to both lethality and mutagenesis by DBE and DBM is a property shared by other DNA alkyltransferases. This objective was accomplished by quantifying the induction of mutations and lethal events in ogt- ada- E. coli expressing an exogenous bacterial or mammalian ATase from a multicopy plasmid. Mammalian recombinant ATases enhanced the lethal and mutagenic actions of DBE and suppressed the lack of sensitivity of the vector- transformed bacteria to DBM. In most cases the order of effectiveness of the ATases ranked: murine > human > Ogt > rat. Further comparisons included the full-length Ada ATase from E. coli and a truncated Ada version (T-ada) that retains the O6-methylguanine binding domain of the protein. The full-length Ada ATase was effective in enhancing the lethality but not the mutagenicity induced by DBE and DBM. The T-ada ATase provided less sensitization than Ada to lethality by DBE, but of the three bacterial ATases T-ada yielded the highest sensitization to mutagenesis by this compound. T-ada and Ada ATases were in general less effective than the mammalian versions, with the exception of the rat recombinant ATase. The effectiveness of the different mammalian and bacterial ATases in promoting the deleterious actions of dibromoalkanes was compared with the effectiveness of these proteins in suppressing the lethal and mutagenic effects induced by N-nitroso-N-methylurea. The ability to sensitize E. coli to the lethal and mutagenic effects of DBE and DBM seems restricted to DNA alkyltransferase, since overexpression of thioredoxin (Trx) or glutaredoxin (Grx1) in ogt- ada- cells showed no effect, in spite of the reported potential of bioactive dihaloethane- derived species to alkylate Trx.      

Hepatic leiomyomas in two adult patients with AIDS: intravenous contrast-enhanced CT and MR imaging

Multiple opportunistic infections and neoplasms have been described in the AIDS population over the past 20 years. Four cases of AIDS-related hepatic smooth muscle tumors (leiomyomas) have been described, and of these, three were in children. The fourth case was in a single patient with two hepatic lesions. We describe the imaging features of two adult cases with biopsy-proven hepatic leiomyomas. In one of the cases, the gadolinium-enhanced MRI findings are described, which have not previously been reported. Electronic Publication     

Analysis of early failure of tunneled hemodialysis catheters

OBJECTIVE: Tunneled hemodialysis catheters are often placed by the interventional radiology service using sonographic guidance and fluoroscopy for safe and optimal placement. The aim of this study was to determine the causes of early failure (相似文献   

Hospital-acquired urinary tract infection

From 16,534 admissions, 60 patients, 4 days to 15 years of age, with one or more hospital-acquired urinary tract infections were identified during a 5-year period by a prospective surveillance system. The patient charts were subsequently reviewed to characterize the population at risk for such infections and to describe the course and consequences of these infections. Infections in individual patients ranged from one to greater than 50. The hospital-acquired urinary tract infection rate for the study period was 14.2 infections per 1,000 admissions. In the patients in whom all urinary tract infections were well documented, the following characteristics were defined: (1) 92% (97 of 105) of the infections occurred in catheterized patients; (2) almost half (49 of 105) of the infections occurred in patients exposed to only intermittent catheterization; (3) 28% (29 of 105) of the infections were asymptomatic; (4) fever was the most frequent finding in the symptomatic patients and occurred in 66% (60 of 105); (5) pyuria was found in only 51% (35 of 69) of the urinalyses performed at diagnosis; (6) 85% (89 of 105) of the infections were single-organism infections; (7) 82% (101 of 123) of the causative organisms were Escherichia coli, Pseudomonas sp, coagulase-negative staphylococci, Enterococcus spp, Klebsiella spp, or Enterobacter sp. The urinary tract infections in the 60 patients were not complicated by bacteremia, and no direct relationship between the infections and the minimal mortality in our patients could be established.