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Biomedical subjects

M W Miller

Publications and source records attributed to M W Miller.

At least 307 records · Page 17Linked to original sources

60 Hz electric field parameters associated with the perturbation of a eukaryotic cell system.

Roots of Pisum sativum were exposed for seven days to 60 Hz electric fields ranging from 70--430 V/m in an aqueous medium whose conductivity was approximately 0.07 mho/m. (Corresponding current densities in the exposure medium associated with these field strengths ranged from 0.5--3.0 mA/cm2). Control and exposed roots were grown concomitantly in the same tank whose growth medium was continuously circulated. Temperature in the exposure medium was held at a constant 19 degrees C. All experiments were conducted "double blind." Root growth rates were determined daily. No perturbations in root growth were observed with electric fields of 150 V/m; there was a slight effect at 360 V/m, and a pronounced decrease in growth rate occurred at 430 V/m. Root conductivities are comparable to that of the growth medium. Under conditions in which growth inhibition occurs, it is estimated that induced 60 Hz cell membrane potentials would be of the order of 3--8 mV.

Electric Conductivity↗

Lack of effect of electric field exposure on rats: a data re-evaluation.

Three recent investigations of the possible effects of to Hz electric fields on rats have yielded apparently contradictory results. While one group of investigators reported that chronic exposure to a 15 kV/m field caused several biological effects, the other two groups did not find these effects at 25 kV/m and 100 kV/m, respectively. A re-examination of the data from the 15 kV/m experiments indicates that the reported effects were probably artifacts due to improper statistical analysis and to a cage design which resulted in transient electric shocks (spark discharges) to the exposed rats. Hence, the results of all three investigations are consistent with a lack of biological effects from chronic exposure to 15--100 kV/m electric fields.

Animals↗

Anticoccidial derivatives of 6-azauracil. 3. Synthesis, high activity, and short plasma half-life of 1-phenyl-6-azauracils containing sulfonamide substituents.

A series of 1-phenyl-6-azauracils containing sulfonamide substituents was prepared. In contrast to previous 1-phenyl-6-azauracils, some of these sulfonamides combine high activity against Eimeria tenella infections in chickens with a very rapid rate of clearance from plasma. Most active was 1-[3'-chloro-5'-methyl-4'-(morpholinylsulfonyl)phenyl]-6-azauracil, with a minimum effective concentration in feed of about 10 ppm.

Animals↗

Effects of dietary proteins from a variety of sources on plasma lipids and lipoproteins of rats.

Five experiments were conducted to study the effect of various protein sources on fasting blood lipids and lipoproteins in the rat. Plasma levels of total cholesterol, high density lipoprotein (HDL)-cholesterol and total triglyceride, as well as weight gain, food intake protein efficiency ratio and net protein utilization were measured over 28-day test periods with male Sprague-Dawley rats. The purified proteins studied included casein, egg albumin, lactalbumin, soy and alfalfa. Crude proteins studied included yeast, fish meal and blood meal. Diets low in methionine were supplemented with this amino acid to insure that all diets were nutritionally adequate. Although the plasma total cholesterol levels varied by 40-50% and HDL-cholesterol by 90% among the various diets, the changes were not associated with any particular dietary protein source or level. Plasma total triglyceride levels varied independently of the dietary source and level of protein. Plasma HDL-cholesterol accounted for approximately 70% of the plasma total cholesterol. Plasma HDL-cholesterol concentrations correlated positively (R = 0.72) with plasma total cholesterol and negatively (R = -0.34) with plasma triglyceride levels. These results clearly show that the pure and crude plant proteins did not have a hypocholesterolemic effect compared with pure and crude animal proteins in rats. Plasma HDL-cholesterol levels were the same in rats fed plant and animal proteins.

Animals↗

H-2-linked genetic control of murine T-cell-mediated lympholysis to autologous cells modified with low concentrations of trinitrobenzene sulfonate.

Spleen cells from B10.BR and C57BL/10 (B10) mice were compared for their ability to generate primary in vitro cytotoxic responses to syngeneic cells modified with different concentrations (from 10 to 0.031 mM) of trinitrobenzene sulfonate (TNBS) (TNP-self). Although both strains generated effector cells to TNP-self in the range of 10-0.25 mM TNBS modification, effector activity of B10 cells was weaker than that of B10.BR cells. B10 spleen cells did not respond to syngeneic stimulating cells modified at 0.1 mM or lower, whereas B10.BR cells generated effector activity even when stimulated by TNP-self modified with as low as 0.031 mM TNBS. Fluorescence analysis of the modified cells using the FACS II indicated that equivalent quantities of TNP were conjugated to the surfaces of B10.BR and B10 spleen cells for any given concentration of TNBS modification. Similar strain-dependent differences were observed when the TNP was diluted out in the cultures by reducing the number of stimulating cells modified with 10 mM TNBS. These response patterns were verified by stimulating cultures of B10.BR and B10 spleen cells either with TNP conjugated to bovine serum albumin or bovine gamma globulin (B10.BR but not B10 cells responded to TNP-conjugated proteins) or with TNBS-modified glass-adherent spleen cells. The strain-dependent differences could also be detected at the effector phase, because optimally stimulated B10.BR, but not B10 effector cells, could lyse 0.1 mM TNBS-modified syngeneic target cells. The genetic parameters associated with the response and nonresponse patterns of B10.BR and B10 mice were further investigated by comparing the cytotoxic responses to low doses of TNP-self of spleen cells from the following strains: (a) C3H/HeJ (H-2k) and C3H.SW (H-2b); (b) BALB.K (H-2k) and BALb.b (h-2b); and (c) B10.A (H-2a) and B10.D2 (H-2d). The H-2k and H-2a, but not the H-2b and H-2d, strains generated cytotoxic responses to TNP-self when the syngeneic stimulators were modified with 0.1 mM TNBS. Further studies using (B10 X B10.BR)F1 responding cells and parental or F1-modified stimulating cells, indicated that the F1 cells generated cytotoxic activity to low doses of TNP in association with H-2k but not in association with H-2b self products. The results of this study indicate that H-2-linked genetic factors, expressed in the target as well as in the responding and/or stimulating cell populations, control the ability of inbred mouse strains to generate cytotoxic effector cells to low doses of TNP-self. Such dose-dependent genetic effects may be important in the regulation of immune responses activated in vivo by chronic exposure to infectious agents.

Animals↗

Anticoccidial derivatives of 6-azauracil. 2. High potency and long plasma life of N1-phenyl structures.

Attachment of substituted phenyl side chains at N1 of 6-azauracil caused striking increases in plasma life and anticoccidial potency. The increases were related in part to the acidity of the imide hydrogen. Maximum effects were shown by phenyl rings substituted in both meta positions by compact, electron-withdrawing, lipophilic substituents, as in 1-(3',5'-dichlorophenyl)-6-azauracil, which had plasma half-life of 160 h and a potency 250-fold greater than that of 6-azauracil.

Animals↗

The absence of an effect of photoreactivation on sub-lethal damage accumulation in a photoreactive wallaby cell-line.

Monolayer cultures of JU56 wallaby cells were exposed to germicidal U.V. and/or photoreactivating (PR) light. The U.V. exposures induced dose-dependent cell-death. The survival data are consistent with a common extrapolation number (n) of 6 x 17 +/- 0 x 98 with a D(0) of 123 x 0 +/- 6 x 8 erg/mm2 for photo-reactivated cells and a D0 of 87 x 3 +/- 4 x 9 erg/mm2 for non-photoreactivated cells; the photoreactivation protected the cells with a dose-modification factor of 1 x 41 +/- 0 x 02. Therefore PR is not a shoulder phenomenon and so has no relationship to the repair of sub-lethal damage.

Animals↗

Anticoccidial derivatives of 6-azauracil. 1. Enhancement of activity by benzylation of nitrogen-1. Observations on the design of nucleotide analogues in chemotherapy.

Benzylation of 6-azauracil at N-1 (which corresponds to the point of attachment of the ribose phosphate unit in pyrimidine nucleotides) has been found to augment its anticoccidial activity fourfold. The high potency of 1-benzyl-6-azauracil is ascribed to a combination of intrinsic activity, efficient oral absorption, and a moderate rate of excretion. Metabolism experiments using 1-benzyl-6-azauracil labeled with 14C in the heterocycle and (separately) in the side chain showed that, in the drug accounted for, no cleavage had occurred. Additional activity increases were achieved by introducing small, electron-withdrawing substituents in the meta and/or para position(s) of the benzyl group. One of the most active derivaties, 1-(3-cyanobenzyl)-6-azauracil, is about 16 times as potent as 6-azauracil.

Animals↗