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T D White

Publications and source records attributed to T D White.

At least 37 records · Page 2Linked to original sources
PubMed1997

A comparison of (+/-)epibatidine with NMDA in releasing [3H]noradrenaline and adenosine from slices of rat hippocampus and parietal cortex.

We compared (+/-)epibatidine with N-methyl-D-aspartate (NMDA) in releasing adenosine and [3H]noradrenaline from slices of rat hippocampus and parietal cortex. (+/-)Epibatidine (0.1 microM) released [3H]noradrenaline but not adenosine from hippocampal slices incubated either with or without extracellular Mg2+. In contrast, NMDA (300 microM) released much more [3H]noradrenaline and also adenosine from hippocampal slices incubated in medium lacking Mg2+. (+/-)Epibatidine released neither adenosine nor [3H]noradrenaline from slices of rat parietal cortex, in contrast to NMDA which released both substances. These findings suggest that those behavioral responses to (+/-)epibatidine that are mediated by noradrenaline may involve the hippocampus but not the parietal cortex. Moreover, it seems unlikely that any of the behavioral effects of (+/-)epibatidine are mediated by adenosine release in either the parietal cortex or the hippocampus.

Adenosine↗
PubMed1997

The first skull of Australopithecus boisei.

Australopithecus boisei was first described from a cranium recovered in 1959 from Olduvai Gorge, Tanzania. This and subsequent finds, mostly from Kenya's Turkana basin, resulted in its characterization as a specialized Australopithecus species with a hyper-robust masticatory apparatus. A distinct A. boisei facial morphology has been emphasized to differentiate robust Australopithecus lineages from East and South Africa. A preference for closed and/or wet habitats has been hypothesized. Here we report some new A. boisei specimens, including the taxon's first cranium and associated mandible, from Konso, Ethiopia. These fossils extend the known geographical range of A. boisei. They provide clear evidence for the coexistence of A. boisei and Homo erectus within a predominantly dry grassland environment. The A. boisei specimens from Konso demonstrate considerable morphological variation within the species. The unexpected combination of cranial and facial features of this skull cautions against the excessive taxonomic splitting of early hominids based on morphological detail documented in small and/or geographically restricted samples.

Animals↗
PubMed1997

The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine.

The purine nucleoside adenosine (9-beta-D-ribofuranosyladenine) inhibits a number of lymphocyte functions in vitro, including the ability of activated T lymphocytes and natural killer cells to adhere to and kill tumor targets. Solid tumors, such as adenocarcinomas of the lung and colon, are frequently hypoxic and are, therefore, likely to exhibit increased adenine nucleotide breakdown through the 5'-nucleotidase pathway, yielding adenosine. We examined whether the concentration of adenosine in the extracellular fluid of such tumors is adequate to cause immunosuppression. Murine tumors grown in syngeneic hosts or human tumors grown in immunodeficient nu/nu mice were subjected to microdialysis, and adenosine levels in the microdialysate were measured by high-performance liquid chromatography. Treatment of the tumor microdialysates with adenosine deaminase eliminated the adenosine peak. Recovery of adenosine ranged from 15 to 29%, depending on the microdialysis probe, and concentrations of adenosine in tumors ranged from 0.2 to 2.4 microM with a mean of 0.5 microM. In contrast, the adenosine concentration measured s.c. at the same location was 30 +/- 5 nM (mean +/- SE). Inclusion of the adenosine deaminase inhibitor coformycin (10 microM) and the adenosine kinase inhibitor 5'-iodotubercidin (0.1 microM) in the microdialysis perfusion buffer increased extracellular adenosine concentration in tumors to as high as 13 microM. These data show that extracellular adenosine levels in solid tumors are sufficient to suppress the local antitumor immune response and that interference with pathways of adenosine metabolism causes marked increases in tumor extracellular adenosine concentration.

Adenosine↗
PubMed1997

Substance P releases and augments the morphine-evoked release of adenosine from spinal cord.

The effects of substance P on the morphine-evoked release of adenosine were examined. Substance P alone produced a multiphasic effect on release of adenosine, with release occurring at low nanomolar concentrations and at a micromolar concentration, but not at intermediate concentrations. An inactive dose of substance P augmented the morphine-evoked release of adenosine at a nanomolar concentration of morphine. Release of adenosine by substance P alone (1 nM) or substance P/morphine (100 nM/10 nM) was Ca2(+)-dependent and originated from capsaicin-sensitive nerve terminals.

Adenosine↗
PubMed1997

Brief communication: prehistoric dentistry in the American southwest: a drilled canine from Sky Aerie, Colorado.

A prehistoric Native American mandible from a Fremont site (circa AD 1025) in Colorado has a conical pit in the worn occlusal surface of the lower right canine. Natural causes for this modification are ruled out by the presence of internal striae, a finding confirmed by experimental replication. The canine was artificially drilled before the individual's death and is associated with a periapical abscess. This is one of a very few examples of prehistoric dentistry in the world, and the first from the American Southwest.

Adult↗
PubMed1997

M3 muscarinic receptor-mediated enhancement of NMDA-evoked adenosine release in rat cortical slices in vitro.

Acetylcholine plays an important role in cortical arousal. Adenosine is released during increased metabolism and has been suggested to be a sleep-promoting factor. To understand the interaction of acetylcholine and adenosine in regulating cortical excitability, we examined the effect of carbachol on NMDA-evoked adenosine release and identified the muscarinic receptor subtype that mediated this effect in adult rat cortical slices in vitro. Carbachol (to 300 microM) alone did not affect the basal release of adenosine. However, carbachol (100 microM) induced a 253% increase in NMDA (20 microM)-evoked adenosine release in the presence of Mg2+. In the absence of Mg2+, carbachol's potentiating effect was less (60% increase). The nonselective muscarinic antagonist atropine (1.5 microM) blocked the facilitatory effect of carbachol on NMDA-evoked adenosine release, and this was mimicked by the M3-selective antagonist 4-diphenylacetoxy-N-methylpiperidine (1 microM). Neither an M1-selective dose of pirenzepine (50 nM) nor the M2-selective antagonist methoctramine (1 microM) affected carbachol's action on NMDA-evoked adenosine release. Carbachol had no effect on adenosine release evoked by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA). These results suggest that acetylcholine does not affect basal adenosine release but enhances NMDA receptor-mediated evoked adenosine release by acting at M3 receptors in the cortex. This interaction may have a role in regulating cortical neuronal excitability on a long-term basis.

Adenosine↗
PubMed1996

Adenosine kinase inhibitors augment release of adenosine from spinal cord slices.

Inhibitors of adenosine kinase, but not adenosine deaminase, produce antinociception when administered spinally. In this study, we evaluated the relative contribution of adenosine kinase and adenosine deaminase to the regulation of adenosine release into the extracellular space within the spinal cord by determining the effects of the adenosine kinase inhibitors 5'-amino-5'-deoxyadenosine and 5-iodotubercidin, and the adenosine deaminase inhibitor 2'-deoxycoformycin on adenosine release from spinal cord slices in an in vitro perfusion system. Both 5'-amino-5'-deoxyadenosine (5-50 microM) and 5-iodotubercidin (5-50 microM), but not 2'-deoxycoformycin (50 microM), augmented adenosine release. 5-Iodotubercidin was slightly more potent and effective than 5'-amino-5'-deoxyadenosine in augmenting release except at the highest concentration, where it was considerably more effective. Combinations of 2'-deoxycoformycin (50 microM) and minimally active concentrations of 5'-amino-5'-deoxyadenosine and 5-iodotubercidin (5 microM each) produced a synergistic enhancement of release. These results support a predominant involvement of adenosine kinase in regulating extracellular adenosine levels in the spinal cord, but adenosine deaminase also can play a significant role.

Adenosine↗
PubMed1996

Potentiation of excitatory amino acid-evoked adenosine release from rat cortex by inhibitors of adenosine kinase and adenosine deaminase and by acadesine.

Endogenous extracellular adenosine provides some protection against excitotoxicity in the central nervous system, but it appears to be incomplete. Potentiating the formation of extracellular adenosine that occurs when excitatory amino acid receptors are activated might provide additional protection. We studied the effects of AICAR (AICA riboside, acadesine) and of inhibitors of adenosine metabolism on the release of adenosine from rat cortical slices. AICAR had no effects on basal N-methyl-D-aspartate (NMDA)- or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxasole propionic acid (AMPA)-evoked adenosine release, but it increased kainate-evoked adenosine release 1.4-fold. This selective action of AICAR may make it useful for treating kainate receptor-mediated excitotoxicity. Inhibition of adenosine kinase with either 20 microM 5'-amino-5'-deoxyadenosine or 5'-iodotubercidin had a much greater effect on excitatory amino acid-evoked adenosine release than on basal adenosine release. Inhibition of adenosine kinase increased excitatory amino acid-evoked adenosine release 3-7-fold whereas inhibition of adenosine deaminase only increased evoked adenosine release 2-2.5-fold. Finally, 0.2 microM 5'-iodotubercidin and 200 microM 2'-deoxycoformycin caused similar increases in the basal rates of extracellular adenosine formation, but 5'-iodotubercidin produced over twice as much potentiation of the rate of NMDA-evoked adenosine formation than did 2'-deoxycoformycin. These findings suggest that adenosine kinase inhibitors may produce an event-specific potentiation of evoked adenosine formation, i.e. more effect on evoked formation than on basal formation. If so, adenosine kinase inhibitors may prove useful for preventing/treating diseases associated with excessive excitation in the brain, such as seizures, excitotoxicity and neurodegeneration.

Adenosine↗
PubMed1996

Synergy between mu/delta-opioid receptors mediates adenosine release from spinal cord synaptosomes.

Morphine releases adenosine from the spinal cord and this contributes to spinal antinociception. The present study examined possible interactions between mu- and subclasses of delta-opioid receptors in the release of adenosine. Nanomolar (10(-8), 10(-9) M) concentrations of morphine release adenosine from spinal cord synaptosomes under conditions of partial depolarization with elevated K+, and this component of release is mediated by activation of mu-opioid receptors. Subnanomolar (10(-10), 10(-11) M) concentrations of the mu-opioid receptor agonists morphine, [N-MePhe3,D-Pro4]morphiceptin, and [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) have minimal effects on the release of adenosine from the spinal cord. However, [D-Pen2,D-Pen5]enkephalin (DPDPE), a delta 1-opioid receptor agonist, and [D-Ala2,Cys4]deltorphin, a delta 2-opioid receptor agonist, at doses which exhibit no intrinsic effects (10(-8) and 10(-7) M), shifted the dose-response curve for mu-opioid receptor-evoked adenosine release to the left in a dose-dependent manner. DPDPE was more potent than [D-Ala2,Cys4]deltorphin when combined with the highly selective mu-opioid receptor agonist [N-MePhe3,D-Pro4]morphiceptin, but these agents showed similar activity with the less selective agonists DAMGO and morphine. Simultaneous activation of mu- and delta-opioid receptors generates a synergistic release of adenosine from spinal cord synaptosomes. Although agonists for both delta 1- and delta 2-opioid receptor subtypes produce this response, the delta 1-opioid receptor agonist is more potent at eliciting this effect when the most selective mu-opioid receptor ligand is used.

Adenosine↗
PubMed1996

Mandibular postcanine dentition from the Shungura Formation, Ethiopia: crown morphology, taxonomic allocations, and Plio-Pleistocene hominid evolution.

Over 200 hominid specimens were recovered by the International Omo Expedition of 1967-1976. Despite the fragmentary nature of this primarily dental collection, these hominid remains represent a major body of evidence about hominid evolution in eastern Africa during the 2-3 myr time period. Our analysis of the Omo dental collection is based on a large comparative sample of 375 quantifiable mandibular postcanine teeth of A. afarensis, A. africanus, A. aethiopicus, A. boisei, A. robustus, and early Homo. A total of 48 isolated mandibular premolars and molars of the Omo collection spanning the 2-3 myr time period is sufficiently preserved to allow reliable serial allocations and intertaxon comparisons and is the object of study in this paper. We present taxonomic identifications of these teeth and seven other mandibular specimens preserving tooth crowns. Metric analyses of this study include cusp area and crown shape variables taken on occlusal view diagrams. Nonmetric analyses were based on simultaneous observations of all relevant material to ensure accuracy of categorical evaluations. First, a combined metric and morphological evaluation was conducted to allocate each Omo tooth to either robust or nonrobust categories. Further taxonomic affinities were then examined. Our results indicate that nonrobust and robust lineages cooccur by circa 2.7 myr. We consider the Shungura robust specimens from Members C through F to represent A. aethiopicus. A significant phenetic transformation occurs at circa 2.3 myr, with the mosaic emergence of the derived A. boisei morphology across Member G times. Characterization of the East African nonrobust lineage is more difficult because of the comparatively subtle morphological differences seen among the dentitions of A. afarensis, A. africanus, and early Homo. The earlier Members B and C nonrobust specimens are difficult to evaluate and are considered indeterminate to genus or species. Both molars and premolars from Members E through G exhibit phenetic similarities to the early Homo condition and are considered as aff. Homo sp. indet. At present, there is no indication of multiple species in the Omo nonrobust sample at any time horizon. The 2-2.4 myr Omo nonrobust specimens exhibit some similarities to the stated Homo "rudolfensis" condition in size and morphology and are likely to represent the ancestral condition of the genus Homo. The bearing of these results on interpretations of early hominid evolution and diversification is considered.

Animals↗
PubMed1995

Modulation of adenosine release from rat spinal cord by adenosine deaminase and adenosine kinase inhibitors.

Adenosine, a modulator of pain processing in the spinal cord, is metabolized by adenosine kinase and adenosine deaminase. In this study we determined which of these mechanisms is more important for the regulation of endogenous adenosine levels in the rat spinal cord. The effects of the adenosine kinase inhibitors, 5'-amino-5'-deoxyadenosine (NH2dAD) and iodotubercidin (IOT), and the adenosine deaminase inhibitor, 2'-deoxycoformycin (DCF), on adenosine release in a spinal cord superfusion model were studied. DCF markedly increased basal adenosine levels detected in perfusates and was more potent than NH2dAD and IOT in this regard. Coadministration of DCF with NH2dAD produced an enhanced effect compared to the inhibitors alone. NH2dAD, but not DCF, potentiated morphine-evoked adenosine release. These results suggest that adenosine deaminase may be the predominant pathway for adenosine metabolism in this experimental model.

Adenosine↗
PubMed1995

Spinal opioid receptors and adenosine release: neurochemical and behavioral characterization of opioid subtypes.

Release of adenosine from the spinal cord contributes to spinal antinociception by morphine. Morphine induces a Ca(++)-dependent release of adenosine from dorsal spinal cord synaptosomes, which is augmented under partially depolarizing conditions. The present study examined the opioid receptor subtypes involved in this release, and determined whether adenosine is an important mediator of antinociception induced by the spinal administration of selective opioid agonists in rats. Nanomolar and micromolar concentrations of the selective mu opioid agonists DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin) and PLO17 ([N-MePhe3,D-Pro4]morphiceptin) induced release of adenosine in a biphasic manner in the presence of a partial depolarization (addition of 6 mM K+ to the Krebs' medium). The delta opioid agonists DPDPE ([D-Pen2,D-Pen5]enkephalin) and DELT ([D-Ala2,Cys4]deltorphin) and the kappa opioid agonist U50488H (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrroli-zemeacetamid e) had little effect on the release of adenosine except at high micromolar concentrations. Release of adenosine by mu (nanomolar) and delta (micromolar) ligands is Ca(++)-dependent, whereas the kappa (micromolar) receptor ligand releases adenosine via a Ca(++)-independent mechanism. Behavioral antinociception using the hot-plate threshold test revealed that intrathecal administration of the mu and delta opioid receptor agonists produced dose-dependent antinociception with an order of potency of DAMGO, PLO17 > morphine, DELT > DPDPE. An ED75 dose of morphine, DAMGO or PLO17 was attenuated dose-dependently by intrathecal pretreatment with the adenosine receptor antagonist caffeine. Caffeine did not block the antinociceptive response to delta agonists, but in fact augmented antinociception when combined with DPDPE and DELT. This augmentation was dose-dependent. This study demonstrates that activation of the mu receptor subtype is responsible for the opioid-induced release of adenosine from the spinal cord, that such release contributes to the spinal antinociception by mu agonists and that only release evoked by low doses of opioids is behaviorally relevant.

Adenosine↗
PubMed1994

Australopithecus ramidus, a new species of early hominid from Aramis, Ethiopia.

Seventeen hominoid fossils recovered from Pliocene strata at Aramis, Middle Awash, Ethiopia make up a series comprising dental, cranial and postcranial specimens dated to around 4.4 million years ago. When compared with Australopithecus afarensis and with modern and fossil apes the Aramis fossil hominids are recognized as a new species of Australopithecus--A. ramidus sp. nov. The antiquity and primitive morphology of A. ramidus suggests that it represents a long-sought potential root species for the Hominidae.

Adult↗
PubMed1994

Ecological and temporal placement of early Pliocene hominids at Aramis, Ethiopia.

Sedimentary deposits in the Middle Awash research area of Ethiopia's Afar depression have yielded vertebrate fossils including the most ancient hominids known. Radioisotopic dating, geochemical analysis of interbedded volcanic ashes and biochronological considerations place the hominid-bearing deposits at around 4.4 million years of age. Sedimentological, botanical and faunal evidence suggests a wooded habitat for the Aramis hominids.

Animals↗
PubMed1994

Is cyclic AMP involved in excitatory amino acid-evoked adenosine release from rat cortical slices?

Activation of both N-methyl-D-aspartate (NMDA) and non-NMDA receptors releases endogenous adenosine from superfused rat cortical slices. NMDA-evoked adenosine release is Ca(2+)-dependent and results from the extracellular degradation of a released nucleotide, whereas non-NMDA receptor activation releases adenosine per se in a Ca(2+)-independent manner. IBMX selectively inhibits NMDA- but not non-NMDA-evoked adenosine release. Forskolin, but not 1,9-dideoxy-forskolin, produced a slight but significant increase in NMDA-evoked adenosine release, suggesting that the formation of cyclic AMP may somehow be involved. The inhibition of NMDA-evoked adenosine release by IBMX is not accompanied by enhanced cyclic AMP recovery in superfusates, nor is release diminished when cyclic AMP transport is inhibited by probenecid, suggesting that the adenosine is not derived from the extracellular metabolism of released cyclic AMP. It is possible that 5'AMP, derived from the intracellular conversion of cyclic AMP by phosphodiesterase, might be released during NMDA receptor activation. However, more selective inhibitors of the specific phosphodiesterase isozymes known to be located in the cortex failed to diminish NMDA-evoked adenosine release. Therefore, the effects of both forskolin and IBMX on NMDA-evoked adenosine release could be nonspecific, coincidental and unrelated to their actions on cyclic AMP levels in the cortex. However, it is also possible that a novel IBMX-sensitive phosphodiesterase plays a primary role in converting cyclic AMP to 5'AMP intracellularly during NMDA receptor activation; the 5'AMP could then exit the cells and be converted to adenosine extracellularly.

1-Methyl-3-isobutylxanthine↗
PubMed1994

African Homo erectus: old radiometric ages and young Oldowan assemblages in the Middle Awash Valley, Ethiopia.

Fossils and artifacts recovered from the middle Awash Valley of Ethiopia's Afar depression sample the Middle Pleistocene transition from Homo erectus to Homo sapiens. Ar/Ar ages, biostratigraphy, and tephrachronology from this area indicate that the Pleistocene Bodo hominid cranium and newer specimens are approximately 0.6 million years old. Only Oldowan chopper and flake assemblages are present in the lower stratigraphic units, but Acheulean bifacial artifacts are consistently prevalent and widespread in directly overlying deposits. This technological transition is related to a shift in sedimentary regime, supporting the hypothesis that Middle Pleistocene Oldowan assemblages represent a behavioral facies of the Acheulean industrial complex.

Animals↗
PubMed1994

Further analysis of mandibular molar crown and cusp areas in Pliocene and early Pleistocene hominids.

Crown and cusp areas of mandibular molars were measured and analyzed on a sample of 249 specimens attributed to Australopithecus afarensis, A. africanus, A. (Paranthropus) robustus, A. (P.) boisei, and early Homo. In addition to intertaxon comparisons, we compared data that had been collected independently by two of the authors using methods that differ slightly in technique of measurement. Interobserver differences were evaluated by the t-test of paired comparisons, method error statistic, percent differences, and principal component analysis. Results suggest that between-technique error of measurement of overall crown area is small. Error estimates for individual cusp area measurements were of larger relative magnitude. However, these were not sufficient to detract from the conclusions derived from comparative analyses. Our results are in general agreement with previous assessments of early hominid dental size. Crown areas of A. africanus, however, exhibit a mosaic pattern, with M1 similar in size to that of A. afarensis and early Homo, and M2 and M3 similar in size to that of A. robustus. Intertaxon comparisons of relative cusp area were undertaken by univariate statistics and principal component analysis. These analyses revealed that while A. (P.) robustus and A. (P.) boisei both possess mandibular molars with cusp proportions significantly different from the 'non-robust' taxa, these differences are substantially greater in A. (P.) boisei.

Analysis of Variance↗