PubMed Health⌕ Search

Biomedical subjects

M W Newton

Publications and source records attributed to M W Newton.

11 recordsLinked to original sources
PubMed2001

Anatolian tree rings and a new chronology for the east Mediterranean Bronze-Iron Ages.

We report an extensive program of high-precision radiocarbon dating to establish the best date for a floating 1599-year Anatolian tree ring chronology that spans the later third millennium B.C. through the earlier first millennium B.C. This chronology is directly associated with a number of key sites and ancient personages. A previously suggested dating is withdrawn and is replaced by a robust new date fix 22 (+4 or -7) years earlier. These new radiocarbon wiggle-matched dates offer a unique independent resource for establishing the precise chronology of the ancient Near East and Aegean and help resolve, among others, a long-standing debate in favor of the so-called Middle Mesopotamian chronology.

Archaeology↗
PubMed2001

Regional 14CO2 offsets in the troposphere: magnitude, mechanisms, and consequences.

Radiocarbon dating methods typically assume that there are no significant tropospheric (14)CO(2) gradients within the low- to mid-latitude zone of the Northern Hemisphere. Comparison of tree ring (14)C data from southern Germany and Anatolia supports this assumption in general but also documents episodes of significant short-term regional (14)CO(2) offsets. We suggest that the offset is caused by an enhanced seasonal (14)CO(2) cycle, with seasonally peaked flux of stratospheric (14)C into the troposphere during periods of low solar magnetic activity, coinciding with substantial atmospheric cooling. Short-term episodes of regional (14)CO(2) offsets are important to palaeoclimate studies and to high-resolution archaeological dating.

Archaeology↗
PubMed1986

Effects of chronic dietary administration of the cholinergic false precursor N-amino-N,N-dimethylaminoethanol on behavior and cholinergic parameters in rats.

The choline analog, N-amino-N,N-dimethylaminoethanol (NADe), was fed ad libitum (chloride salt; 0.5%) to weanling rats in a low choline, low methionine synthetic diet. Control rats were fed choline chloride (0.5%) in place of NADe. Initial observation and behavioral screen tests of grasp strength, startle reflex, righting reflex, analgesia (hot plate test) and body temperature did not reveal any toxic effects caused by NADe, although both experimental and control groups gained weight more slowly than rats fed standard lab chow. After 25 days on the diet, the performance of rats fed NADe in a one-trial passive avoidance test was significantly impaired compared to control rats. There was no difference between experimental and control rats in sensitivity to foot shock or in activity monitored in a closed field. A subjective, 6-component behavioral rating scale indicated rats fed NADe were resistant to handling but not aggressive. These behavioral results were similar in two separate feeding experiments using deuterium-labeled and unlabeled NADe. The twitch response of isolated rat phrenic nerve-diaphragms during stimulation did not show any impairment of neuromuscular function in rats fed NADe. Receptor binding experiments indicated there were no differences between experimental and control rats in tritiated quinuclidinyl benzilate [( 3H]QNB) binding capacity in cortex, heart and ileum. Competitive [3H]QNB binding with carbachol indicated there was no difference in the IC50's measured in cortex homogenates. Acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities in cortex were similar in experimental and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1985

Acetyl-N-aminodeanol: a cholinergic false transmitter in rat phrenic nerve-diaphragm and guinea-pig myenteric plexus preparations.

The metabolism of the choline analog N-amino-N,N-dimethylaminoethanol (N-aminodeanol) by isolated rat diaphragm and guinea-pig myenteric plexus preparations and the pharmacological properties of the acetate ester were studied. Deuterium-labeled N-aminodeanol was transported and acetylated by rat diaphragm and guinea-pig myenteric plexus preparations. Diaphragms stimulated indirectly in the presence of [2H4]N-aminodeanol (2 X 10(-5) M) released [2H4]acetyl-N-aminodeanol at 38% the rate at which [2H4]acetylcholine was released from controls incubated with [2H4]choline (2 X 10(-5) M). In the guinea-pig myenteric plexus, [2H4]acetyl-N-aminodeanol was synthesized and released at a rate up to 70% that measured for [2H4] acetylcholine. N-methylatropine (10(-7) M) enhanced the stimulated release of [2H4]acetyl-N-aminodeanol and [2H4] acetylcholine (in separate controls) by the same amount (2,3-fold). After incubation in the presence of [2H4]N-aminodeanol, [2H4]acetyl-N-aminodeanol replaced (mole for mole) 17 and 50% of the endogenous acetylcholine tissue content in diaphragm and myenteric plexus, respectively. As the tissue [2H0]acetylcholine was replaced, its release was reduced to 38 and 22% of control in diaphragm and myenteric plexus, respectively. Combined transmitter release (true + false) was reduced to 56 to 79% of release from controls. Endogenous choline efflux apparently limited the replacement of true with false transmitter in these preparations. Acetyl-N-aminodeanol had 4 and 17% the potency of acetylcholine on the guinea-pig ileum and frog rectus abdominis preparations, respectively. These findings indicate that [2H4]N-aminodeanol forms a false transmitter in rat diaphragm and guinea-pig myenteric plexus and may potentially interfere with cholinergic function. Effective replacement of endogenous acetylcholine in vivo would also require replacement of endogenous sources of choline for transmitter synthesis.

Acetylcholine↗
PubMed1985

Metabolism and subcellular distribution of N-amino-N,N-dimethylaminoethanol (N-aminodeanol) in rat striatal synaptosomes.

The metabolism and subcellular distribution of a novel choline analog, N-amino-N,N-dimethylaminoethanol (N-aminodeanol) in rat striatal synaptosomes was studied using combined gas chromatography mass spectrometry for simultaneous estimation of N-aminodeanol, choline, tracer choline and their acetate esters. The enzymes choline acetyltransferase, acetylcholinesterase and choline kinase were assayed in kinetic studies using N-aminodeanol or acetyl-N-aminodeanol as substrates. The results demonstrate that [2H4]N-aminodeanol is transported and acetylated in synaptosomes at rates approximately 30% of those measured for [2H4]choline. Of the [2H4]N-aminodeanol that was transported by the high affinity choline uptake system, the proportion acetylated was similar to that measured for [2H4]choline. [2H4]Acetyl-N-aminodeanol replaced endogenous acetylcholine stores and was released. The combined release of endogenous and false transmitters from synaptosomes in the presence of [2H4]N-aminodeanol was reduced compared to controls in the presence of [2H4]choline, although combined tissue stores did not change significantly. After coincubation with [2H4]N-aminodeanol and [2H4]choline, the molar ratios of true and false transmitter in the tissue appeared to reflect the kinetic parameters for high affinity transport of the precursors. Subcellular fractionation experiments indicated that [2H4]acetyl-N-aminodeanol was incorporated into vesicles more slowly than [2H4]acetylcholine. These results indicate that the reduced rate of turnover in the presence of false precursor is not due to its rate of acetylation or to the rate of release of previously formed false transmitter, but rather to the slower membrane transport of N-aminodeanol by the high affinity uptake system. The replacement of endogenous acetylcholine in synaptosomes by acetyl-N-aminodeanol, which has 4% the potency of acetylcholine at muscarinic receptors, suggests that N-aminodeanol may be useful in studying the in vivo effects of a false cholinergic transmitter.

Acetylation↗
PubMed1985

In vivo metabolism of a cholinergic false precursor after dietary administration to rats.

The false cholinergic precursor [2H4]N-amino-N,N-dimethylaminoethanol (N-aminodeanol, NADe) was fed ad libitum to weanling rats in a low choline (Ch), low methionine synthetic diet. The free [2H4]NADe plasma concentration achieved at 32 days was 51 microM. The free Ch plasma concentration was reduced to 6 microM, compared to 20 microM measured in control rats which were fed Ch in place of [2H4]NADe. After 33 days the rats were killed by rapid microwave fixation, and tissues were assayed for [2H4]NADe, [2H0]Ch and their acetate esters using combined gas chromatography mass spectrometry. Approximately 50% of the acetylcholine content of cortex, striatum, hippocampus, diaphragm and ileum had been replaced by the false transmitter [2H4]O-acetyl-N-aminodeanol. In all tissues measured except striatum the sum of the true + false transmitters was not significantly different from the acetylcholine content in control rats. In striatum the sum of the transmitters was significantly reduced to 79% of control. [2H4]NADe was incorporated into lipids. The ratio of lipid bound [2H4]NADe to lipid bound Ch in the plasma of experimental rats was 2.6. In cortex, the ratio of lipid bound [2H4]NADe to lipid bound Ch (1.3) was comparable to the ratio of false to true transmitter (1.0), although the ratio of free [2H4]NADe to free Ch was much higher (4.9). NADe caused no obvious toxicity, although both control and experimental groups gained weight more slowly than rats fed standard laboratory chow. These results demonstrate that NADe can enter the biochemical pathways for Ch in vivo, causing replacement of endogenous acetylcholine with the false transmitter acetyl-NADe.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1983

Rapid decline in acetylcholine release and content of rat extensor digitorum longus muscle after denervation.

The amount of acetylcholine (ACh) and choline (Ch) in normal and denervated rat extensor digitorum longus (EDL) muscles, as well as that released spontaneously from these muscles, was determined by an extremely sensitive gas chromatographic-mass spectrometric assay method. We found decreases in ACh content and spontaneous, resting ACh release as early as 8 h after denervation. The ACh content decreased to a plateau of 30% of control by 11 h; ACh release attained a plateau of 50% of control several hours later. These results showed that in denervated EDL muscles ACh content and spontaneous release (measured biochemically) decreased before nerve-evoked and spontaneous quantal release (measured physiologically) ceased at most synapses. The rapid reduction in ACh, or possibly in other substances that may be released with ACh, may be an important factor in initiating postsynaptic degenerative changes after nerve transection. Choline content and choline resting release increased significantly at both 1 and 3 days after nerve transection. These increases may be related to onset of postsynaptic neuromuscular degenerative changes.

Acetylcholine↗
PubMed1983

The effect of beta-bungarotoxin on acetylcholine and choline content of vertebrate tissues.

We have investigated the effects of intraventricularly or i.p. administered beta-bungarotoxin on the tissue content of acetylcholine and choline in three vertebrate species. A gas chromatographic mass spectrometric assay was used to measure acetylcholine and choline. Intraventricular administration of beta-bungarotoxin (1 microgram, 105 min) in rats raised the acetylcholine content of hippocampus and striatum but not of cortex. Choline was significantly increased in all three brain regions. Injection of the toxin i.p. (5 micrograms, 90 min) in rats caused variable increases of the acetylcholine content of diaphragm, tongue, temporalis muscle and adrenal gland, but no significant change was seen in heart atrium, eye, ileum or superior cervical ganglion. Significant increases of choline content were seen in heart and adrenal. The toxin caused the same degree of increase of acetylcholine in mouse diaphragm as in the rat. No alteration of sartorius muscle or tongue acetylcholine was observed after i.p. injection of beta-bungarotoxin (5 micrograms) in frog. Results with 125I-labelled beta-bungarotoxin (rats, i.p.) suggest that the observed differences in response to beta-bungarotoxin cannot be accounted for by the distribution of toxin alone. From these data we make suggestions regarding the variable effects of beta-bungarotoxin on tissue acetylcholine and choline content and the implication of these findings for the mechanism of action of the toxin.

Acetylcholine↗
PubMed1981

Beta-bungarotoxin stimulates the synthesis and accumulation of acetylcholine in rat phrenic nerve diaphragm preparations.

1. The effects of beta-bungarotoxin on acetylcholine (ACh) synthesis, tissue content and release have been studied in the rat diaphragm. A gas chromatographic mass spectrometric assay was used to measure ACh and choline. 2. Within 30 min, beta-bungarotoxin (0.14 or 1.4 micrograms/ml.) caused a significant increase in tissue ACh content. This increase was apparent prior to the final inhibition by beta-bungarotoxin of evoked (10 Hz) ACh release. 3. The toxin enhanced the incorporation of [2H4]Ch into [2H4]ACh in both resting and stimulated preparations. 4. Hemicholinium-3 blocked the rise in diaphragm ACh normally produced by beta-bungarotoxin. 5. Beta-Bungarotoxin did not directly activate choline acetyltransferase in muscle homogenates. 6. The toxin-induced rise in tissue ACh was largely absent in Ca2+-free solutions which contained either EGTA (1 mM) or SrCl2 (2 or 10 mM). 7. Non-neurotoxic phospholipases A2, fatty acids and the neurotoxic phospholipase A2, notexin, did not cause ACh accumulation in the diaphragm. 8. Beta-Bungarotoxin did not stimulate ACh synthesis in denervated muscle. 9. The extra ACh which accumulated after beta-bungarotoxin did not contribute to enhanced release by nerve impulses even when 4-aminopyridine was added to the medium. High K+ solution and black widow spider venom were also ineffective in increasing output from toxin-treated diaphragms relative to controls that had not been treated with beta-bungarotoxin. 10. Prior injection of a rat with botulinum toxin prevented the accumulation of ACh due to beta-bungarotoxin. Tubocurarine, however, did not antagonize beta-bungarotoxin. 11. These data indicate that beta-bungarotoxin has a unique capacity to inhibit ACh release and stimulate ACh synthesis in diaphragm nerve endings. The results are discussed in terms of a possible action of beta-bungarotoxin to raise the level of ionized Ca in the nerve terminal cytosol.

Acetylcholine↗