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D Bechtel

Publications and source records attributed to D Bechtel.

10 recordsLinked to original sources

Lack of UDS activity in the livers of rats exposed to allylisothiocyanate.

Allylisothiocyanate (AITC) has been evaluated for its ability to initiate unscheduled DNA synthesis (UDS) in the livers of male rats in vivo. Specific Pathogen Free outbred albino Hsd/Ola Sprague-Dawley rats were exposed by oral gavage to 37.5 or 125 mg/kg AITC in corn oil and hepatocytes assessed for UDS by autoradiography 2 and 14 h later. AITC did not induce UDS at either dose level at either time point. These data are consistent with all other evidence indicating that AITC does not act as a genotoxin in vivo, despite positive response in some in vitro screening assays. The reported occurrence of benign bladder papillomas in male rats but not female rats or mice of either sex is consistent with non-genotoxic action and may be attributed to chronic irritation of the bladder epithelium by AITC and its cysteine conjugate metabolite excreted by male rats in unusually concentrated form. It is concluded that the weight of evidence is insufficient to regard AITC as a genotoxin capable of human carcinogenicity.

Animals↗

Effects of type and amount of dietary fat on mouse skin tumor promotion.

In a previous study (Cancer Res 51, 907, 1991) in which we found an inverse relationship between quantity of dietary corn oil and saturated fat, in a constant 15% fat diet, on the tumor promotion stage of skin carcinogenesis, it was not clear whether one or both types of fat played a modulatory role. The purpose of the present study therefore was to compare the effect of 1) increasing corn oil in corn oil-only diets and 2) increasing saturated fat, with a constant level of 5% corn oil, on tumor promotion. In the first study, the effects of five levels of dietary corn oil (5%, 10%, 15%, 20%, and 25%) on the incidence and rat of papilloma and carcinoma development were determined in female Sencar mice fed these diets one week after initiation with 7,12-dimethylbenz[a]anthracene and three weeks before the start of promotion with 12-O-tetradecanoylphorbol-13-acetate. A papilloma incidence of 100% was reached first in the 5% corn oil group, at 10 weeks, followed by the 10% group at 13 weeks and the 15% and 20% group at 16 weeks. The highest corn oil group achieved a 90% incidence. There were marked differences in latency of carcinoma development among the diet groups. At Week 29, the cumulative carcinoma incidence was 56% and 32%, respectively, in the 5% and 10% corn oil groups, whereas the incidence in the two highest corn oil (20% and 25%) groups was only 8% and 4%, respectively. In the second study, the effects of diets containing 5% corn oil and increasing levels of coconut oil (5%, 10%, 15%, and 20%) on the incidence and rat of papilloma and carcinoma development were determined, as described above. No significant difference in latency or incidence of papillomas or carcinomas was noted among these saturated fat diet groups. It thus appears that higher levels of dietary corn oil are associated with a reduced cancer incidence in this model system.

Animals↗

Effects of type of dietary fat on phorbol ester-elicited tumor promotion and other events in mouse skin.

Based on the biological activity of arachidonic acid metabolites, we hypothesized that alterations in the consumption of linoleic acid, the precursor to arachidonic acid, would result in a modification in tumor development when fed during the tumor promotion stage of the mouse skin initiation-promotion model. The effects of seven different levels of dietary linoleic acid (LA), supplied as corn oil in a 15% fat diet, on the incidence and rate of papilloma and carcinoma development were determined. SENCAR mice were placed on one of the experimental diets, containing 1.0, 3.6, 6.0, 7.9, 9.9, 12.5, or 15.0% corn oil, 1 week after initiation with 10 nmol of 7,12-dimethylbenz(a)anthracene and 3 weeks prior to the start of twice weekly promotion with 1 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA). At 15 weeks of TPA treatment there were significant differences in papilloma number among diet groups, such that an inverse correlation (r = 0.92) was observed between tumor number and level of corn oil; the lowest corn oil diet group had an average of 11.7 tumors/mouse, while the highest corn oil group had 5.4 tumors/mouse. However, there was little difference in tumor incidence among diet groups. A general relationship between diet and carcinoma incidence was also found, such that the highest corn oil diet group had the lowest carcinoma incidence. In an experiment performed with DBA/2 mice, the average number of papillomas/mouse at 17 weeks was 4.5 (1.0% corn oil), 5.6 (7.9%) corn oil), and 2.3 (15.0% corn oil). Papilloma incidence was also affected by diet, with a 79% incidence for the 15.0% corn oil and an incidence of 93% for the 1.0% corn oil group. analyses of the fatty acid composition of epidermal phospholipids in mice fed the experimental diets reflected the dietary LA levels, in that an accumulation of phospholipid LA, accompanied by an overall decrease in arachidonic acid, occurred with increasing dietary corn oil. In spite of the high membrane levels of LA, no measurable amount of epidermal conjugated dienes of LA could be detected. Epidermal prostaglandin E2 levels in acetone-treated mice were similar for all diet groups (approximately 3 pg/micrograms DNA). However, 6 h after topical application with 4 micrograms of TPA, prostaglandin E2 levels were elevated 5- to 10-fold; an inverse correlation (P less than 0.05) was seen with increasing dietary LA, although the concordance with decreased phospholipid arachidonic acid was not strong.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗

Clinical utility of the MMPI in the evaluation of adolescent suicide attempters.

MMPI profiles of female adolescents hospitalized on a general pediatrics floor following a suicide attempt were compared to a control group of medically hospitalized, female adolescents referred for psychiatric evaluation. The suicide attempters had only a lower score on the K scale when compared to the control group. Results do not suggest that a single MMPI profile differentiates suicide attempters from a comparison group of adolescents with emotional difficulties. Implications of these findings are discussed.

Adolescent↗

Postextrasystolic potentiation as a predictor of potential myocardial viability: preoperative analyses compared with studies after coronary bypass surgery.

The ability to predict reversibility of ventricular dysfunction should be important in determining operability. This study examined the usefulness of postextrasystolic potentiation as such a predictor. Left ventricular wall motion was studied using cineventriculography in 31 patients before and after revascularization surgery. Preoperative ejection fraction and wall motion were analyzed during a sinus beat and after a random ventricular extrasystole, whereas postoperative ejection fraction and wall motion were examined only during a sinus beat. Changes in ventricular motion were correlated with changes in vascular supply achieved by operation. Of the 7 patients whose ejection fraction was improved postoperatively, 6 had shown postextrasystolic potentiation compared with only 10 of the 24 patients without such improvement (P less than 0.05). Regional wall motion analysis also showed a significant association between postextrasystolic potentiation and postoperative improvement in wall motion. Of 26 zones judged to have an increased vascular supply after operation, 11 showed increased motion postoperatively. All 11 had shown postextrasystolic potentiation, compared with only 5 of 15 zones with increased vascular supply but without increased postoperative motion (P less than 0.001). Thus, postextrasystolic potentiation seems to be a useful predictor of the ability of asynergic myocardium to respond to successful revascularization surgery.

Adult↗

Abnormalities of left ventricular function and geometry in adults with an atrial septal defect. Ventriculographic, hemodynamic and echocardiographic studies.

Left ventricular function and motion in 12 adults with an ostium secundum atrial septal defect were analyzed utilizing biplane cineangiography. Values for left ventricular end-diastolic volume index, stroke volume index, ejection fraction, left ventricular end-diastolic pressure and mean rate of circumferential fiber shortening were compared with values in an age-matched group of 11 normal subjects. Comparisons of ventriculographic and echocardiographic data were also made in 5 patients and 10 control subjects. Cardiac index was smaller in patients than in the normal subjects (3.6 vs. 4.5 liters/min per m2, P less than 0.01). Although left ventricular end-diastolic pressure was similar (8 mm Hg in both groups), the end-diastolic volume index was significantly smaller in patients than in normal subjects (56 vs. 76 ml/m2, P less than 0.05). Stroke volume index was also significantly smaller in patients (40 vs. 52 ml/m2, P less than 0.01). The two groups had similar values for ejection fraction (65 +/- 2 percent [standard error of the mean] in patients vs. 68 +/- 2 percent in normal subjects), circumferential fiber shortening velocity (1.67 +/- 0.13 vs. 1.81 +/- 0.15 circumferences/sec.), heart rate (91 +/- 7 vs. 90 +/- 5 beats/min) and mean systemic arterial pressure (92 +/- 5 vs. 87 +/- 3 mm Hg). Early systolic bulging of the upper ventricular septum toward the right ventricle was seen in 10 of 12 patients with an atrial septal defect but in no normal subject. Echocardiographic data supported these findings. No other abnormalities of motion were consistently noted. It is concluded that the left ventricle of patients with an atrial septal defect is subnormal in volume and abnormal in sequence of contraction of the septum and is characterized by apparent decreased distensibility.

Adolescent↗

Liposomal bleomycin: increased therapeutic activity and decreased pulmonary toxicity in mice.

Conventional and sterically stabilized liposomes derived from phosphatidylcholine or the antitumor agents, hexadecylphosphocholine and octadecyl-(1,1-dimethyl-4-piperidino-4-yl)-phosphate, as bilayer forming constituents, containing bleomycin, were developed and tested. Liposomal encapsulation of bleomycin enhanced strongly the antitumor activity against P388 leukemia and the Lewis lung carcinoma. This effect was clearly dependent on the size and lipid composition of the bleomycin-containing liposomes. The therapeutic effects were nearly equal for liposomal and free bleomycin in the B16 melanoma. The partial replacement of phosphatidylcholine by alkylphospholipids and the inclusion of polyethylene glycol modified lipids for sterical stabilization did not further improve the therapeutic efficacy but increased, in some cases, the toxicity of liposomes. Bleomycin-induced lung injury was not observed if liposomal bleomycin was administered.

Animals↗