Biomedical subjects

T C Jenkins

Publications and source records attributed to T C Jenkins.

At least 91 records · Page 5Linked to original sources

PubMed1995

Butylsoyamide protects soybean oil from ruminal biohydrogenation: effects of butylsoyamide on plasma fatty acids and nutrient digestion in sheep.

Based on previous results showing partial resistance of fatty acyl amides to ruminal biohydrogenation, butylsoyamide was added to sheep diets in an attempt to increase unsaturation of plasma fatty acids. Twelve wethers averaging 34 +/- 3.2 kg BW were randomly assigned to three diets containing either no added fat (control), 5% soybean oil, or 5% butylsoyamide. Dry matter intake was greater (P < .05) for sheep fed butylsoyamide than for sheep fed soybean oil (740 and 581 g/d, respectively), but neither fat supplement differed from the control diet (680 g/d). The soybean oil supplement reduced (P < .05) total VFA concentration (59.0 and 38.7 mM) and acetate:propionate (4.10 and 2.56) in ruminal samples compared with the control diet. Butylsoyamide had no effect (P > .05) on total VFA (54.4 mM) or acetate:propionate (2.96). Total tract ADF digestibility was not affected (P > .05) by either fat supplement. Relative to the control diet, soybean oil increased (P < .05) plasma linoleic acid concentration 22% compared with a 58% increase from feeding butylsoyamide (26.7, 32.6, and 42.1% of total fatty acids, respectively). Linoleic acid concentration in plasma neutral lipids, relative to the control diet, increased 15.8% (P < .05) for soybean oil compared with 64.9% (P < .05) for butylsoyamide (31.6, 36.6, and 52.1% of total fatty acids, respectively). Converting soybean oil triglycerides to fatty acyl amides substantially reduces negative effects of the oil on ruminal fermentation and increases unsaturated fatty acids in plasma. The increase in plasma unsaturated fatty acids demonstrates at least partial resistance of fatty acyl amides to ruminal biohydrogenation and their digestion and absorption postruminally.

Animal Feed↗

PubMed1995

Fixation disparity and near visual acuity.

Twenty patients having associated heterophoria values of 2 delta and greater, as recorded with a Mallett unit, had their near monocular and binocular visual acuities measured. In the latter case, measurements were taken both with the associated heterophoria corrected by prisms and without prism correction. Bradford Near Vision charts, specially designed to measure visual acuity at near in seconds of arc, were used in the acuity measurement. The improvement of binocular acuity compared with monocular acuity was less than would occur in normal subjects without associated heterophorias. When the associated heterophorias were corrected with prisms the improvement in binocular over monocular acuity was similar to that found in normal subjects, with zero associated heterophoria readings.

Adolescent↗

PubMed1994

Structure of a covalent DNA minor groove adduct with a pyrrolobenzodiazepine dimer: evidence for sequence-specific interstrand cross-linking.

The structure of the interstrand cross-linked adduct formed between a C8-C8'-linked pyrrolobenzodiazepine (PBD) dimer (DSB-120; 1,1'-(propane-1,3-diyldioxy)bis[(11aS)-7-methoxy-1,2,3,11a-t etrahydro-5H- pyrrolo[2,1-c][1,4]benzodiazepin-5-one]) and a self-complementary d(CICGATCICG)2 duplex has been determined from high-field 1D- and 2D-NMR data using a simulated annealing procedure. The refined structure supports earlier observations from solution NMR experiments and indicates that the covalently bound molecule spans six DNA base pairs in the minor groove, forming a symmetric cross-link between the spatially separated internal guanines and with active recognition of an embedded 5'-GATC bonding site. This result confirms that template-directed approaches are useful for the design of linked DNA-interactive PBD dimers with viable DNA cross-linking potential. Further, head-to-head connection of the PBD moieties results in an overall retention of 5'-GA bonding site preference for each alkylating PBD subunit. Structural analysis indicates that cross-link formation results in a localized perturbation of the DNA duplex, attributable in part to a mutual reduction in dynamic mobility or "covalent clamping" within the Gua4-Cyt7 base tract. However, ligand-induced distortion is confined to the Cyt7 and Ino8 residues on each strand. The Gua(N2)-Gua(N2) cross-link is stabilized by two directed H-bonds from the formed animal residues to N3 acceptor atoms of adenine bases on the 3'-side of each covalently modified guanine. Evidence for sequence-specific cross-linking with DSB-120 is provided by extended modeling studies which suggest that recognition of the favored d(.GATC.) motif is dominated by van der Waals steric factors, although electrostatic and H-bonded interaction terms also play a key role. This conclusion supports recent covalent footprinting studies revealing that this PBD dimer shows a selectivity for embedded base sequences of the type 5'-(pu/py)GATC(py/pu).

Base Sequence↗

PubMed1994

Crystal structure of gamma-oxapentamidine complexed with d(CGCGAATTCGCG)2. The effects of drug structural change on DNA minor-groove recognition.

The crystal structure of the complex of gamma-oxapentamidine and the DNA dodecamer d(CGCGAATTCGCG)2 has been determined to a resolution of 0.22 nm and an R factor of 18.9%. The gamma-oxapentamidine ligand interacts with the dodecamer by classic minor groove binding via interactions within the A+T-rich region of the minor groove. A chain of solvent molecules lies along the mouth of the minor groove on the outside of the bound ligand. The structural details of the complex are discussed and compared with the closely analogous complex with pentamidine bound to the same dodecamer [Edwards, K. J., Jenkins, T. C. & Neidle, S. (1992) Biochemistry 31, 7104-7109]. The amidinium groups of the ligand do not hydrogen bond to bases, but are in close contact with O4' sugar ring atoms. This in part explains the reduced DNA binding affinity of this ligand compared to pentamidine.

Antifungal Agents↗

PubMed1994

Effect of dietary lipid supplementation on progesterone concentration and reproductive performance in suckled beef cows.

Using whole cottonseed as a lipid source, silage-based diets that were isocaloric and isonitrogenous yet varied in lipid level were fed to multiparous cows. In Experiment 1, 48 cows (n = 12 per treatment) were allotted to 1 of 4 treatments where diets were formulated to supply 3.9, 4.3, 5.3 and 6.3% of total lipid. In Experiment 2, 66 cows (n = 22 per treatment) were allotted to 1 of 3 treatments where diets were formulated to supply 3.1, 5.5 and 8.3% of total lipid. Length of the first ovarian cycle, length of the first normal estrous cycle, postpartum intervals to onset of ovarian luteal activity and to first estrus were not affected by diet (P>0.10) in either experiment. Mean progesterone (P(4)) concentrations for first normal estrous cycles were not different (P>0.10) in either experiment. Anestrous periods were divided into 3 phases for analyses: Phase I) parturition to onset of ovarian luteal activity, Phase II) first ovarian luteal activity and Phase III) first normal estrous cycle. No differences were observed in P(4) concentrations during any phase of the postpartum period. In conclusion, isocaloric and isonitrogenous diets with increasing levels of lipid had no effect on reproductive performance in suckled beef in these experiments.

Journal Article↗

PubMed1994

Dietary soybean oil changes lipolytic rate and composition of fatty acids in plasma membranes of ovine adipocytes.

A study was conducted to determine which fatty acids in plasma membranes of adipose tissue from ruminants are changed when the diet is supplemented with unsaturated fatty acids and to determine the effect of the fat supplement on adipocyte metabolism. Ten sheep were randomly assigned to two isonitrogenous diets containing either no added fat (control) or 5 g soybean oil/100 g diet. Perirenal fat was removed at slaughter, adipocytes isolated by collagenase digestion, and plasma membranes prepared by centrifugation on a Percoll gradient. Feeding soybean oil to the sheep increased (P < 0.05) linoleic acid [18: 2(n-6)] concentration in subcutaneous fat and isolated adipocytes, suggesting partial escape of dietary unsaturated fatty acids from ruminal biohydrogenation. Soybean oil consumption also decreased (P < 0.05) concentrations of myristic acid, arachidonic acid [20: 4(n-6)] and anteiso 17:0 in plasma membranes, but increased (P < 0.05) trans 18:1. Lipogenesis was not affected by diet, but lipolysis tended to be greater (P = 0.07) in sheep fed the soybean oil-containing diet than in those fed the control diet. In ruminants, fatty acids of ruminal origin, namely trans intermediates of biohydrogenation or branched-chain fatty acids of microbial lipid, may account for as much change in the composition of plasma membranes and in cellular metabolism as do the small quantities of unsaturated fatty acids in the diet that escape biohydrogenation.

Adipocytes↗

PubMed1994

Regulation of lipid metabolism in the rumen.

Lipid added to animal diets can affect productive efficiency through a combination of caloric and regulatory effects. Any attempt to improve productive efficiency of ruminants by modifying the amount or composition of lipid added to the diet must take into account ruminal metabolism of lipids. The caloric value of lipid is changed little as it passes through the rumen, but the greater concern is the possible negative effect of lipid on the energy value of the basal diet. Limiting unsaturated fatty acids fed to ruminants to just a few percent of the diet to avoid digestive disturbances, combined with extensive hydrogenation by ruminal microbes, maintains only small quantities of unsaturated fatty acids in duodenal contents. However, in some studies, lipid added to ruminant diets has invoked metabolic changes that were not attributable to caloric effects. These metabolic changes suggest that the rumen does not maintain digesta flow with constant lipid composition in all circumstances. Variations in rumen outflow of biohydrogenation intermediates and microbial lipids are as great, or greater in some situations, than unsaturated fatty acids. Diet characteristics, such as amount of grain or unsaturated lipid, can substantially alter the nature of fatty acids absorbed from the duodenum and deposited in animal tissues.

Animals↗

PubMed1994

Effect of fixation disparity on distance binocular visual acuity.

Subjects with appreciable values (2 delta and greater) of associated 'phoria, as measured by a Mallett unit, had their distance monocular and binocular visual acuities measured. In the latter case measurements were taken both with the associated 'phoria corrected by prisms and without such a correction. The improvement in binocular acuity compared to monocular acuity was less than would occur in normal subjects with minimal associated 'phorias although the improvement differed accordingly as to whether the readings were eso- or exo-in mature. When the associated 'phorias were corrected with prisms the improvement in binocular over monocular visual acuity was similar to that found in normal subjects.

Adult↗

PubMed1994

Endocrine responses and body composition changes during feed restriction and realimentation in young bulls.

Changes in serum metabolic hormones, carcass composition, and body weight gains were examined in 21 Angus bulls (9 mo old) subjected to feed restriction and realimentation. They were allotted to three feeding regimens: 1) control (CON); 2) restricted (REST); and 3) realimented (REAL). The CON group was fed 3.2% of their body weight; the REST group was fed 1.5%. The REAL group was fed the restricted diet (1.5% BW) for 84 d then fed the control diet (3.2% BW) until slaughter. The CON and REAL groups were slaughtered at approximately 400 kg and the REST group at 346 kg. For the experiment, average daily gains (kg/d) were different (P < .05) (CON = 1.60; REAL = 1.35; REST = .64). Bulls were bled every 20 min for 6 h on d 14, 70, 98, and 127 of the experiment. Overall carcass characteristics (yield grade, muscle area, marbling) and chemical analysis of 9-10-11 rib sections indicated changes in quantity and percentages of protein and fat commensurate with the dietary intake treatments. The REST group had the least lean and fat (P < .05); the REAL group had less fat than (P < .05) but the same amount of lean (P > .05) as the CON group. Serum GH was higher in the REST than in the CON group (P < .05). In the REAL group, serum GH values rose to a level similar to that of the REST group; realimentation lowered serum GH (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

DNA-binding properties of nitroarene oligopeptides designed as hypoxia-selective agents.

The DNA-binding properties of six candidate nitroarene-functionalized oligopeptides 8-13 (i.e. 5-nitrofuran, 2-nitroimidazole and 4-nitrobenzene derivatives) with potential hypoxia-selective activity, developed as analogues of the archetypal minor groove-binding ligands, netropsin 1 and distamycin 2, have been examined using an extended molecular mechanics and dynamics (MM/MD) modelling approach. The energies calculated for interaction with the d(CGCGAATTCGCG) duplex, or d(CGCAAATTTGCG)2 in the case of the elongated nitrobenzene 13, correlate with fluorimetric data obtained by indirect competitive displacement of ethidium bromide from double-stranded calf thymus DNA. The results suggest that the mode of interaction for these agents resembles the behavior of structurally unrelated bis(amidine) derivatives that also bind to AT-rich stretches of duplex B-DNA via the minor groove. Analysis of the binding behaviour indicates that the interactions are determined by enthalpic rather than entropic energy terms, suggesting that specific or differential hydration effects for the DNA and ligand may be unimportant. A rational structure-activity relationship is established for the interaction of this family of oligopeptides with DNA that also encompass the bis(amidine) class of ligands.

Animals↗

PubMed1993

Crystal structure of d(CGCGAATTCGCG) complexed with propamidine, a short-chain homologue of the drug pentamidine.

The crystal structure of the complex between propamidine and the self-complementary DNA dodecamer d(CGCGAATTCGCG) duplex has been determined to a resolution of 2.1 A and a R-factor of 17.4%. The propamidine binds to the DNA within the minor groove, with specific hydrogen-bonding interactions from the amidinium groups to the bases and sugar groups of the DNA, via a 4-base-pair binding site. A network of water molecules lies over the mouth of the minor groove. The structure provides a rationale for the superior DNA-binding properties of propamidine as compared to pentamidine [cf. Edwards, K. J., Jenkins, T. C. & Neidle, S. (1992) Biochemistry 31, 7104-7109]. This is seen to result from (i) decreased minor groove width at the binding site and (ii) reduced mobility of the bound propamidine molecule.

Base Sequence↗

PubMed1993

A quantitative assay to measure the relative DNA-binding affinity of pyrrolo[2,1-c] [1,4]benzodiazepine (PBD) antitumour antibiotics based on the inhibition of restriction endonuclease BamHI.

An assay has been developed (restriction endonuclease digestion assay--RED100) based on inhibition of the restriction endonuclease BamHI that is capable of quantitative evaluation of the relative DNA-binding affinity of pyrrolo[2,1-c] [1,4]benzodiazepine (PBD) antitumour antibiotics. This method provides comparable results to those obtained from thermal denaturation and ethidium bromide displacement assays but is much more sensitive, discriminating between molecules of similar structure such as DC-81, iso-DC-81 and neothramycin. The results reveal a trend between relative DNA-binding affinity and in vitro cytotoxicity for the PBDs in two tumour cell lines studied.

Animals↗

PubMed1993

NMR and molecular modeling studies of the interaction of berenil and pentamidine with d(CGCAAATTTGCG)2.

The interaction of two anti-trypanosomal agents, berenil and pentamidine, with the A+T-rich dodecamer d(CGCAAATTTGCG)2 has been examined by high-resolution 1H-NMR, optical spectroscopy, and molecular modeling. Proton assignments for the free DNA and each DNA-ligand complex were obtained using nuclear Overhauser enhancement spectroscopy and total correlation spectroscopy. Complexation induces large changes in chemical shift for protons in the DNA minor groove for the A5-T9 segment, and intermolecular NOEs reveal contacts between the DNA bases and each ligand. The asymmetric binding site for berenil indicated by the NMR data suggests that at least two overlapping sites are involved. Rapid exchange between symmetrically-equivalent binding sites, via dissociative rearrangement, is consistent with retention of twofold degeneracy for both the ligand and the DNA host. Calculations of binding energy confirm that this DNA duplex contains overlapping sites of similar binding affinity. In contrast, the larger pentamidine molecule occupies a site that spans four or five bp, with asymmetric binding to the minor-groove 5'-ATTT sequence. The B-type conformation of the DNA is not altered substantially by either ligand.

Base Sequence↗

PubMed1993

Crystal structure of an oligonucleotide duplex containing G.G base pairs: influence of mispairing on DNA backbone conformation.

The structure of the G.G mispaired dodecanucleotide d(CGCGAATTGGCG)2 has been solved by x-ray crystallography and refined to an R factor of 18.8% at 2.2 A resolution for 3513 reflections. The dodecamer crystallizes as a B-type DNA double helix. It contains two G(anti).G(syn) base pairs--i.e., G-4/G-16(anti).G-21/G-9(syn). The Hoogsteen base pairing involves atoms O-6 and N-7 of the guanine in the syn conformation with atoms N-1 and N-2 of the anti-paired purine. One G.G base pair has a bifurcated hydrogen bond between G-4(N-1)...G-21(N-7) and G-4(N-1)...G-21(O-6). There is little overall structural distortion of the double helix induced as a consequence of the mispairing. The helical width is significantly increased by comparison with the structure of the native duplex, and the minor groove width in the 5'-AATT region is decreased. The G.G base pairing induces high-BII phosphate conformations at residues G-9 and T-20 in addition to more normal BII conformations at G-10 and G-22. It is suggested that these backbone aberrations provide signals for the facile repairability of G.G mispairs in DNA.

Base Composition↗

PubMed1993

Metabolism of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) by purified DT-diaphorase under aerobic and anaerobic conditions.

Purified DT-diaphorase [NAD(P)H (quinone acceptor) oxidoreductase (EC.1.6.99.2)] from Walker cells was used to investigate the reductive metabolism of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) under aerobic and anaerobic conditions. In the presence of NADPH, under aerobic conditions, HPLC analysis showed the four-electron reduction product 3-amino-1,2,4-benzotriazine (SR 4330) was the major reaction product. In contrast, anaerobically, the 2-electron reduction product 3-amino-1,2,4-benzotriazine-1-oxide (SR 4317) was the predominant metabolite. Anaerobic reduction of SR 4233 to the known metabolites SR 4317 and SR 4330, catalyzed by DT-diaphorase, was 3-fold higher than reduction under aerobic conditions. Anaerobically, approximately half of the substrate utilized could not be accounted for by the formation of known products. Aerobically, the majority of the SR 4233 lost could be accounted for by its conversion to SR 4317 and SR 4330. In Walker cells incubated with SR 4233 anaerobically, SR 4317 was the major metabolite formed. Dicoumarol (100 microM) had little effect on the rate of formation of this metabolite in this cell line or in a rat liver epithelial derived (JBJ) cell line. Dicoumarol did however partially reduce the induction of unscheduled DNA synthesis caused by SR 4233 in Walker cells but not in JB1 cells, suggesting the action of dicoumarol may be specific to Walker cells. It is concluded that DT-diaphorase plays only a minor role in the overall reduction of SR 4233 in the two cell lines studied.

Anaerobiosis↗

PubMed1993

Effect of induced fixation disparity by negative lenses on the visually evoked potential wave.

The effect of induced fixation disparity produced by negative lenses and base-in prisms on the pattern visually evoked potential (VEP) was investigated. Monocular and binocular pattern reversal VEP were recorded through the negative lenses and base-in prisms using a 9.5 min arc check size. The results suggest that the mean binocular amplitude was 27% larger than the mean monocular amplitude which indicates partial summation in the absence of negative lenses or base-in prisms. A reduction of the binocular VEP amplitude appears to arise in the presence of fixation disparity induced by both the negative lenses and base-in prisms. Both the prisms and the negative lenses had no appreciable effect on the monocular VEP amplitude.

Evoked Potentials, Visual↗

PubMed1993

Lipid metabolism in the rumen.

Recent advances in ruminal lipid metabolism have focused primarily on manipulation of physicochemical events in the rumen aimed at two practical outcomes: 1) control of antimicrobial effects of fatty acids so that additional fat can be fed to ruminants without disruption of ruminal fermentation and digestion and 2) regulation of microbial biohydrogenation to alter the absorption of selected fatty acids that might enhance performance or reduce saturation of meat and milk. Properties of lipids that determine their antimicrobial effects in the rumen include type of functional group, degree of unsaturation, formation of carboxylate salts, and physical association of lipids with surfaces of feed particles and microbes. The mechanism of how lipids interfere with ruminal fermentation is a complex model involving partitioning of lipid into the microbial cell membrane, potency of the lipid to disrupt membrane and cellular function, physical attachment of microbial cells to plant surfaces, and expression and activity of microbial hydrolytic enzymes. Lipolytic and hydrogenation rates vary with forage quality (stage of maturity and N content), surface area of feed particles in the rumen, and structural modifications of the lipid molecule that inhibit attack by bacterial isomerases.

Animals↗

PubMed1993

DNA minor groove recognition properties of pentamidine and its analogs: a molecular modeling study.

A molecular mechanics and molecular dynamics approach has been used to examine the structure of the complex formed between pentamidine and the d(CGCGAATTCGCG)2 duplex. Similar energy calculations have also been performed on complexes with closely related pentamidine analogs, using the complex with the parent drug as the starting point. The resulting structures of the drug-DNA complexes and their energetics have been examined and are compared with the reported DNA binding affinities. These studies provide rationalizations for the differences in binding behavior of pentamidine analogs with differing linker chain lengths and aromatic ring substitutions.

Base Sequence↗