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R A Byrd

Publications and source records attributed to R A Byrd.

51 records · Page 3Linked to original sources
PubMed1985

Nuclear magnetic resonance and circular dichroism studies of a duplex--single-stranded hairpin loop equilibrium for the oligodeoxyribonucleotide sequence d(CGCGATTCGCG).

Nuclear magnetic resonance (NMR) and circular dichroism (CD) studies have been carried out with the oligodeoxyribonucleotide mismatch sequence, d(CGCGATTCGCG), 1. It has been found that 1 exists, in solution, as an equilibrium mixture of slowly interconverting, structured conformational isomers, 1a and 1b. On the basis of the concentration dependence of the 1a-1b equilibrium, the 1H NMR spectrum of the imino protons of the nucleotide bases, and the individual CD spectra of 1a and 1b, it is suggested that the two species correspond to a B-type DNA duplex and a single-stranded, hairpin-loop structure; the portion of the single-stranded species not involved in the loop appears to have a B-type DNA structure (on the basis of the CD measurements). To facilitate 1H NMR resonance assignments, the two possible des-methyl thymidine derivatives of 1 were synthesized; the effect of this substitution on the physical chemical properties of 1 was explored. The 1H NMR spectra of 1, as a function of temperature, showed that, under conditions wherein both species were present to a significant extent, the duplex form melted at a lower temperature than the single-stranded, hairpin loop structure.

Circular Dichroism↗
PubMed1982

A 31P-NMR study of structural and functional aspects of phosphate and phosphonate distribution in Tetrahymena.

31P-NMR has been used to study the chemical nature of cytoplasmic components of live Tetrahymena in a non-invasive manner. The technique has further been used to characterized the physical behaviour of lipids extracted from this organism. In particular, we have shown the presence of large quantities of pyrophosphate and of tripolyphosphate in acid extracts of the organism. These are not detectable in the live cells due to the motionally rigid nature of the storage granules. We have characterized the distribution of phosphonic acids in the organism and followed the phase behavior of the extracted cell lipids. Aqueous dispersions of extracted lipid show both bilayer and non-bilayer behaviour in the range of the growth temperature. The phosphonolipid in Tetrahymena appears to play a role similar to that of phosphatidylethanolamine in regulating the phase behaviour of the membrane. The high degree of unsaturation in the fatty acids of Tetrahymena is most likely responsible for the polymorphic phase behaviour observed near the growth temperature.

Animals↗
PubMed1982

A 2H-NMR study of Acholeplasma laidlawii membranes highly enriched in myristic acid.

Myristic acid specifically deuterated at several positions along the acyl chain was biosynthetically incorporated into the membrane lipids of Acholeplasma laidlawii B to the level of greater than or equal to 90%. 2H-NMR was used to study the molecular order and lipid phase composition of the membranes as a function of temperature. Isolated membranes and intact cells give rise to similar 2H spectra. Below 25 degrees C the spectra exhibit a broad gel phase component which at 0 degrees C reaches the rigid limit value expected for an immobilized methylene group. Spectral moments were used to determine the relative amounts of gel and liquid crystalline phase lipids throughout the gel-liquid crystal phase transition. The results indicate that at the growth temperature (37 or 30 degrees C) the A. laidlawii B membrane lipids are approximately 85-90% in the gel state, and that protein has little effect on lipid order of the liquid crystalline lipid, but leads to an increase in the linewidth by approx. 20%.

Acholeplasma laidlawii↗
PubMed1982

Blood flow during pregnancy in the rat: I. Flow patterns to maternal organs.

Normal blood flow patterns to several maternal organs were characterized in individual CD rats, nonpregnant (NP) or on day 6, 7, 8, 10, 11, 12, 13, 16, 18, or 20 of gestation using the radioactive microsphere technique. Weights and flow values were determined for several uterine tissue samples as well as maternal organs. No significant changes were found in blood flow to the stomach, spleen, and urinary bladder of these animals. There also were no remarkable changes as pregnancy progressed in blood flow to the lungs, suggesting that no marked arterial-venous shunting occurs in maternal placental tissues over gestation. Slight but consistent decreases in absolute (ml/min) and relative (ml/min/g tissue) blood flow to the brain were noted, and percent cardiac output (CO) was significantly decreased on all days of gestation except day 7. Complex changes were observed in blood flow to the kidneys, liver, adrenals, and heart. Absolute flow to the kidneys and liver reached maximum values on day 11, although percent CO delivered to both organs was consistently reduced throughout gestation. Absolute flow to the heart and adrenals peaked on day 13 and days 11-12, respectively. Absolute flow to the ovaries increased nearly 5-fold from the NP state (0.36 +/- 0.11) to day 20 of pregnancy (1.61 +/- 0.33). Interlitter differences in ovarian blood flow during midgestation were found to be a result of differences in litter size and distribution of embryo/fetuses between the two uterine horns. The fact that the majority of changes observed in maternal organ flow coincide with placental development, rapid augmentation of total uterine flow, and/or maternal hormonal changes suggests that these patterns may be important indicators of the dynamic physiology of pregnancy.

Animals↗
PubMed1981

Analysis of the composition of mixed lipid phases by the moments of 2H NMR spectra.

The use of (2)H NMR spectral moments to determine the composition of biphasic lipid mixtures is outlined. The analysis has been applied to phosphatidylethanolamine-cholesterol (1:1), potassium palmitate, 30% (wt/wt) water and phosphatidylcholine-cholesterol (4:1) systems, as well as to membrances of Escherichia coli during phase transitions. The advantages and disadvantages of the use of spectral moments to determine fractions of coexistent phases are discussed.

Cell Membrane↗
PubMed1980

31P NMR studies of vegetative and encysted cells of Acanthamoeba castellanii. Observation of phosphonic acids in live cells.

31P NMR studies have been performed on vegetative and encysted Acanthamoeba castellanii. A prominent feature of the spectra is the presence of resonances characteristic of P-C linkages. Vegetative cells show sharp phosphonate resonances whereas encysted cells show broad phosphonate resonances and narrow phosphate resonances. Studies of model compounds using 31P NMR have shown the narrow resonances to arise from 2-aminoethylphosphonic acid; the broad components from encysted cells arise from molecules with long rotational correlation times such as aggregates of lipophosphonoglycan or phosphonoprotein. Vegetative cells also show the presence of an electronegatively beta-substituted phosphonic acid, possibly 1-hydroxy-2-aminoethylphosphonic acid, a component identified in the cell membrane lipophosphoglycan. pH titration studies of a number of phosphonic acid model compounds show a chemical shift behaviour quite distinct from that of biological phosphates. Upon acidification from pH 12, resonances shift to high field followed by return to lower field at pH 1.0. These resonances can be ambiguous as monitors of cellular pH. The pH of both vegetative and encysted cells is 6.0--6.5. Encysted cells under anaerobic conditions show no spectral changes over 24 h. Vegetative cells under similar conditions show time-dependent changes characteristic of variation in cellular pH. There appears to be little correlation between pH and the variously differentiated states (vegetative or encysted) in Acanthamoeba.

Amoeba↗
PubMedDate not supplied

Developmental toxicity of the dopamine agonist pergolide mesylate in CD-1 mice. I: Gestational exposure.

Pergolide was given by oral gavage to mated CD-1 female mice at doses of 0, 1, 20, or 60 mg/kg/day on gestation days (GD) 6-15. Animals assigned to the teratology segment were killed on GD 18 for evaluation of maternal organ weights, and fetal viability, weights and morphology. Animals assigned to the postnatal segment were allowed to deliver and physical development and behavioral performance of the progeny were monitored until weaning. Maternal organ weights were collected at termination after weaning. One F1 offspring per sex per litter was maintained for postweaning physical, behavioral and reproductive assessments and for terminal examinations and organ weight evaluations. No adverse effects of pergolide treatment were found in the 1 mg/kg/day group. Dose-related hyperactivity, chewing and squinting that were consistent with dopaminergic stimulation occurred following dosing in the 20 and 60 mg/kg/day groups; F0 body weights and food consumption were reduced during the initial phase of treatment in the 60 mg/kg/day group. Gravid uterine weights and fetal weights were decreased in the 60 mg/kg/day group of the teratology segment, but there was no indication of teratogenicity in any group. Mammary inflammation, attributed to increased progeny suckling, occurred during the second week postpartum in a few postnatal segment females of the 20 and 60 mg/kg/day groups. Mean negative geotaxis performance was delayed slightly, but mean progeny survival and body weights were not affected. Although after weaning the F1 offspring from the treatment-derived groups tended to weigh more than controls and to perform more effectively in the active avoidance task, these findings were attributed to unusually low values obtained in the control group. Startle amplitudes were increased significantly in the males from the 60 mg/kg/day treatment-derived group. These dose-related maternal and developmental findings were all consistent with the mixed D1/D2 agonist properties of pergolide mesylate, and suggest that only very high doses may result in persistent effects on the developing central dopaminergic systems.

Aging↗
PubMedDate not supplied

The selective estrogen receptor modulator, raloxifene: reproductive assessments in adult male rats.

Raloxifene HCl is a nonsteroidal, selective estrogen receptor modulator developed for postmenopausal osteoporosis. Reproductive toxicity of raloxifene was examined in adult male CD rats after the oral administration of doses of 0, 10, 30, or 100 mg/kg/d. In the first study, males (12/group) were treated for 2 weeks followed by 2 weeks without treatment. After dose administration on Day 13, 6 males/group were cohabited with untreated females (1:2) for up to 7 d. Males were killed on Day 14 or 28 (6/group each day). Sperm were collected from the right cauda epididymis and evaluated for relative concentration, motion characteristics, and breakage. The kinetics of spermatogenesis were examined by DNA flow cytometry. The left testis and epididymis were preserved for histopathologic evaluation. Females were examined for reproductive status on Gestation Day 13. In a second study, males (20/group) were treated for 7 weeks (4 weeks prior to cohabitation during a 2-week cohabitation period, and for 1 additional week). Treated males were cohabited with untreated females (1:1). On Gestation Day 20, untreated females were examined for reproductive status and fetuses were examined for viability, weight, gender, and morphology. At necropsy, male reproductive tissues were collected, weighed, and preserved for histopathologic evaluation. In both studies, male body weight gain and food consumption were depressed at all dose levels. There was no indication in either study that raloxifene caused important changes in sperm production, sperm quality, or male reproductive performance at doses as high as 100 mg/kg/d.

Administration, Oral↗
PubMedDate not supplied

The selective estrogen receptor modulator, raloxifene: segment II studies in rats and rabbits.

Raloxifene is a nonsteroidal, selective estrogen receptor modulator developed by Eli Lilly and Company primarily as a therapeutic agent for postmenopausal osteoporosis. Two Segment II studies were conducted that examined maternal reproductive parameters and fetal outcome following gestational exposure to raloxifene. Pregnant CD rats (25/group) and New Zealand white rabbits (20/group) were dosed once daily by oral gavage with 0, 0.1, 1, or 10 mg/kg on Gestation Days (GD) 6 through 17 and 7 through 19, respectively. Maternal body weight and food consumption were monitored throughout pregnancy. Caesarean sections were performed on GD 20 and GD 28 for rats and rabbits, respectively, to evaluate fetal viability, weight, and morphology. In rats, maternal body weight, body weight gain, and food consumption were reduced in all raloxifene treatment groups. Fetal viability was depressed in the 10-mg/kg group and was often associated with signs of hemorrhaging from the vagina. Fetal growth retardation was indicated in the 1- and/or 10-mg/kg groups by increased incidences of fetal runts and the developmental deviations, wavy ribs and kidney cavitation. There was no evidence of treatment-related malformations in rat fetuses. In rabbits, depressions in body weight gain and food consumption occurred in the 10-mg/kg group, and a single abortion occurred in the 1-mg/kg group. Fetal viability and weights were not affected in any of the raloxifene treatment groups. The overall proportions of fetuses with malformations, deviations, or variations were not affected by treatment with raloxifene; however, one fetus each from the 0.1-, 1-, and 10-mg/kg groups had incomplete closure of the interventricular septum. Therefore, maternal and fetal no-effect levels were not obtained in this study of raloxifene.

Administration, Oral↗