Variation in response to fescue toxicosis was examined in inbred and linecross mice. In Exp. 1, exposure to a 50% endophyte-infected tall fescue diet (E+) reduced ADG of males from six inbred lines, but ADG of males from one line was modestly higher on E+. Lines differed (P < .01) for reproductive organ weight, but the diet x line interaction was not significant. In Exp. 2, an apparently susceptible (C57) and an apparently resistant line (FVB) were mated to produce inbred and linecross offspring. The reduction in weight gain caused by the E+ diet did not differ significantly among the genetic groups. In Exp. 3, C57 and C57 backcrosses had smaller reductions in ADG during E+ vs control feeding periods than FVB and FVB backcrosses (P < .10). In Exp. 4, the E+ diet reduced litter size of mates of C57 males by one pup, whereas litter size of mates of FVB males was four pups larger (interaction P = .07). Neither diet, line, nor their interaction affected male reproductive organ weights or tissue proportions in testis cross-sections. In Exp. 5, the E+ diet did not affect weight gain of C57 or FVB males, but effects of the E+ diet on litter size of mates were similar to those in Exp. 4. Percentage of abnormal sperm was increased in C57 males on the E+ diet but decreased in FVB males (Exp. 5). Differences among inbred lines in susceptibility to fescue toxicosis may depend on severity of the challenge and life cycle stage when the challenge is imposed.
The activity of beta-glucuronidase is increased in atherosclerotic human arteries (1)(2)(3) . Noting that beta-glucuronidase is a key marker enzyme in evaluating lysosomal enzyme activity, we decided to investigate other lysosomal enzymes in human atherosclerotic vessels. I t was found that in addition to beta-glucuronidase, the lysosomal enzymes, acid phosphatase, cathepsin and aryl sulfatase showed increased activity in human atherosclerotic aortas (4). The present report describes the activities of these four enzymes in the aortas of rabbits in which atherosclerosis has been induced by adding cholesterol to the diet.The effect of cortisone added to the diet has been observed. Cortisone tends to increase the level of serum cholesterol in the cholesterol-fed animals; nevertheless, this compound greatly decreases the intensity of atherosclerosis (5, 6 ) . I t is of interest that cortisone exerts a strong effect on lysosomal membranes (7). We have therefore investigated the effect of cortisone on the activity of the lysosomal enzymes in the cholesterol-fed rabbits.Materials and Methods. Male, white New Zealand rabbits, weighing 2.0 to 2.5 kg were fed the diets ad libitum for a period of 100 days. The control group of 5 rabbits received standard rabbit chow. Another 10 animals were fed the same chow to which was added 1 c/r cholesterol acetate. Of these, five survived the 100-day. period. A third group of 8 rabbits received the cholesterol-containing diet to which was added cortisone acetate to give a concentration of 0.005%]. Of the third group, 5 rabbits were alive a t the end of the experiment. The animals were sacrificed instantly by mechanical means a t 100 days. *Aided by a grant from The William H. Donner Foundation.The aortas were dissected out and scored grossly with a hand lens for atherosclerotic involvenient by two observers working independently. The arch, the thoracic and abdominal portions of the aorta were graded separately on a scale of 1 to 4, and the total score was recorded: 1+ represents fatty streaks and small plaques covering up to 10% of the area; 2+ indicates 10-25%; 3+, 25-50%; 4+ from 50% to total involvement.Representative samples of each portion of the aorta were taken for histologic examination, and the remainder were employed for the enzyme assays. The histological examinations were performed by Dr. M. A. Farooki, Professor of Pathology, Khyber Medical College, Peshawar University, who a t the time of these experiments was Visiting Pathologist at the Philadelphia General Hospital.For the determination of enzyme activities, the aortas were carefully stripped of adventitia. The intima-media residuals were then homogenized by hand in a cold 0.25 M sucrose solution with a glass tissue grinder. The homogenate was centrifuged a t 2520g for 10 min to remove debris. The supernatant was employed for the estimation of the enzyme activities. The enzymic tests were all carried out a t 37". Activities are expressed in units//gram of tissue; 1 unit refers to the decomposition of 1 pg or 1 pmole of ...
Aberrant DNA methylation is commonly heralded as a promising cancer biomarker; however, its inherently stochastic nature often leads to variable methylation patterns that can complicate the use of methylation 2 biomarkers for clinical diagnostics, particularly in dilute samples such as liquid biopsies. Here, we present a methylation density binary classifier, a statistical method for leveraging differential heterogeneous methylation to predict and optimize the performance of methylation biomarkers for clinical applications. We first developed and tested the classifier using methylation density profiles derived from reduced representation bisulfite sequencing reads of ovarian carcinoma at ZNF154, a recurrently methylated locus in multiple cancer types. We then used in silico simulations to predict the performance of the classifier in liquid biopsies and validated these predictions using quasi-digital melt curve analysis (DREAMing) of circulating cell-free DNA from individuals with versus without ovarian carcinoma. We found good agreement between predicted and observed classifier performance, and further demonstrated that implementation of this approach with ZNF154 outperformed CA-125 for use in etiologically-diverse ovarian cancer types. Our results indicate that methylation density profiles can be exploited to predict and facilitate implementation of methylation biomarkers for clinical applications, and that ZNF154 methylation shows promise as a clinicallyuseful biomarker for ovarian cancer.DNA (ctDNA), and associated epigenomic alterations, when shed from cancerous tissues into the blood (4). While whole methylome analyses, such as whole-genome bisulfite sequencing (WGBS) (5) andInfinium BeadArrays (6), have identified scores of differentially-methylated genomic loci in cancers (7), only a handful of individual loci have ultimately become effective for use as biomarkers in clinical applications (8,9). This is due to a number of technical hurdles involved in translating promising methylation biomarkers for use in liquid biopsies, including (i) the small proportion of plasma ctDNA relative to cell-free DNA (cfDNA) derived from healthy cells (10), (ii) heterogeneity of methylation at a given locus (11-14), (iii) age-associated accrual of methylation confounding marker selection (15), and (iv) differences in the yield of extracted tumor subtypes than measurement of blood CA-125, the most commonly-employed biomarker for monitoring EOC. Not only do these results suggest potential as an improved screening method for ovarian cancer, they more broadly offer a practical means of improving the diagnostic performance of DNA methylation-based biomarkers, particularly in challenging samples such as liquid biopsies. MATERIAL AND METHODS Datasets and samples450K Illumina Infinium HumanMethylation450 BeadChip datasets. Processed Illumina Human 450K data for EOCs (GEO accession GSE72021, described in (8)) from 221 tumor samples (171 serous, 18 endometrioid, 14 clear cell, 9 mucinous and 9 other histological cancer subtypes) and W...
1129nism, possibly in conjunction with the normal "erosive'' properties of red blood cell flow. 5. The morphologic characteristics of the injury in v i m , and by histologic sectioning have been described. 6. There is evidence that the endothelial cytoplasm may have phagocytic properties under the conditions of the experiments described here.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.