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Biomedical subjects

E C Miller

Publications and source records attributed to E C Miller.

At least 181 records · Page 10Linked to original sources
PubMed1966

Nucleic acid guanine: reaction with the carcinogen N-acetoxy-2-acetylaminofluorene.

Reaction of N-acetoxy-2-acetylaminofluorene with DNA or RNA at pH 7 causes marked increase in absorption at 280 to 320 millimicrons and marked decrease in guanine content. Reaction with guanosine-8-(14)C yields a radioactive fluorescent derivative. The data suggest that metabolic esters of N-hydroxy-2-acetylaminofluorene may be intermediates in the binding of this proximate carcinogen to nucleic acids in vivo.

Carcinogens↗
PubMedDate not supplied

The metabolic sulfonation and side-chain oxidation of 3'-hydroxyisosafrole in the mouse and its inactivity as a hepatocarcinogen relative to 1'-hydroxysafrole.

The chemically synthesized sulfuric acid esters of 1'-hydroxysafrole and 3'-hydroxyisosafrole, 1'-sulfooxysafrole and 3'-sulfooxyisosafrole, respectively, are both strong electrophiles. Each ester reacted with deoxyguanosine (dGuo) in aqueous solution to form both safrol-1'-yl- and isosafrol-3'-yl-deoxyguanosine adducts. Both 1'-hydroxysafrole and 3'-hydroxyisosafrole were also formed from each ester in the presence of water. When either 1'-[3H]hydroxysafrole or 3'-[3H]hydroxyisosafrole was incubated with mouse liver cytosols fortified with 3'-phosphoadenosine-5'-phosphosulfate (PAPS) and RNA, similar levels of RNA- and protein-bound adducts were formed; thus, the hepatic sulfotransferase activities for these two substrates appear to be similar. In contrast, the levels of hepatic nucleic acid and protein adducts formed after administration of 3'-[3H]hydroxyisosafrole to mice were only 2-4% and 8-14%, respectively, of those obtained after an equimolar dose of 1'-[3H]hydroxysafrole. Likewise, when 3'-hydroxyisosafrole was injected into 12-day-old male B6C3F1 mice at a level of 0.1 or 2.5 mumol/g body wt., the average numbers of hepatomas per mouse (0.2 and 0.4, respectively) were not significantly increased over the average number for mice treated only with the solvent (0.2). By contrast, mice that received 0.1 mumol of 1'-hydroxysafrole/g body wt. developed about 2 hepatomas per mouse. The metabolism of 3'-hydroxyisosafrole in the rat and mouse differed markedly from that of 1'-hydroxysafrole. 3'-Hydroxyisosafrole rapidly underwent side-chain oxidation to yield 3,4-methylenedioxycinnamic acid and 3,4-methylenedioxybenzoic acid. In the first 4 h, 3,4-methylenedioxybenzoyl glycine and 3,4-methylenedioxycinnamoyl glycine, the major urinary metabolites, together accounted for 39% and 63% of the dose administered to rats and mice, respectively. The glucuronide of 3'-hydroxyisosafrole was not detected in the urine, whereas urinary excretion of the glucuronide of 1'-hydroxysafrole at 2 h accounted for approx. 40% of a dose of 1'-hydroxysafrole.

Animals↗
PubMedDate not supplied

Utilizing clinical factors to reduce head CT scan ordering for minor head trauma patients.

Our study objective was to determine whether simple clinical criteria can be used to safely reduce the number of patients who require cranial computed tomography (CT) scan after sustaining minor head trauma. Awake patients (Glascow Coma Scale = 15) who presented to the emergency department with acute head injury associated with a loss of consciousness were evaluated for clinical predictors of head injury prior to CT scan. The studied risk factors included severe headache, nausea, vomiting, and depressed skull fracture on physical examination. Patients with no risk factors present were compared with patients with one or more risk factors with respect to abnormal CT rate and rate of operative intervention for head injury. Of the 2143 patients entered into the study, 1302 (61%) had no risk factor for head injury, whereas 841 (39%) had one or more risk factors present. A total of 138 (6.4%) of those studied had an abnormal CT scan. This number included 3.7% of those patients with no risk factors vs. 11% in patients with one or more risk factors. The CT scan abnormalities in the no-risk-factor group were not clinically significant. All 5 patients who required operative intervention had at least one of the risk factors present. The use of four simple clinical criteria in minor head trauma patients would allow a 61% reduction in the number of head CT scans performed and still identify all patients who require neurosurgical intervention and the majority of patients with an abnormal CT scan. This method could lead to a large savings in patient charges nationwide. Further studies may be helpful in confirming these findings.

Adult↗