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K L Thomas

Publications and source records attributed to K L Thomas.

At least 37 records · Page 2Linked to original sources
PubMed1994

Aqueous alteration of the Bali CV3 chondrite: evidence from mineralogy, mineral chemistry, and oxygen isotopic compositions.

A petrographic, geochemical, and oxygen isotopic study of the Bali CV3 carbonaceous chondrite revealed that the meteorite has undergone extensive deformation and aqueous alteration on its parent body. Deformation textures are common and include flattened chondrules, a well-developed foliation, and the presence of distinctive (100) planar defects in olivine. The occurrence of alteration products associated with the planar defects indicates that the deformation features formed prior to the episode of aqueous alteration. The secondary minerals produced during the alteration event include well-crystallized Mg-rich saponite, framboidal magnetite, and Ca-phosphates. The alteration products are not homogeneously distributed throughout the meteorite, but occur in regions adjacent to relatively unaltered material, such as veins of altered material following the foliation. The alteration assemblage formed under oxidizing conditions at relatively low temperatures (<100 degrees C). Altered regions in Bali have higher Na, Ca, and P contents than unaltered regions which suggests that the fluid phase carried significant dissolved solids. Oxygen isotopic compositions for unaltered regions in Bali fall within the field for other CV3 whole-rocks, however, the oxygen isotopic compositions of the heavily altered material lie in the region for the CM and CR chondrites. The heavy-isotope enrichment of the altered regions in Bali suggest alteration conditions similar to those for the petrographic type-2 carbonaceous chondrites.

Calcium Phosphates↗
PubMed1994

Spatial and temporal changes in signal transduction pathways during LTP.

Following LTP induction in freely moving rats, in situ hybridization revealed discrete changes in the expression of one isoform in each of four families of serine/threonine kinases constitutively expressed in the dentate gyrus of the hippocampus. Expression of the alpha isoform of CaMKII showed a transient increase over the soma and a more persistent increase over the dendritic field of dentate granule cells. Of the PKC isoforms, only gamma PKC was up-regulated substantially 2 hr after LTP induction, declining to control levels 48 hr later. An increase in the expression of mRNA for ERK2 and raf-B was seen at 24 hr only. These results show that, during the maintenance phase of LTP in the hippocampus, there are selective increases in the expression of serine/threonine kinases and that these increases have specific and characteristic temporal and spatial profiles.

Animals↗
PubMed1993

Molecular characterization of a peripheral receptor for cannabinoids.

The major active ingredient of marijuana, delta 9-tetrahydrocannabinol (delta 9-THC), has been used as a psychoactive agent for thousands of years. Marijuana, and delta 9-THC, also exert a wide range of other effects including analgesia, anti-inflammation, immunosuppression, anticonvulsion, alleviation of intraocular pressure in glaucoma, and attenuation of vomiting. The clinical application of cannabinoids has, however, been limited by their psychoactive effects, and this has led to interest in the biochemical bases of their action. Progress stemmed initially from the synthesis of potent derivatives of delta 9-THC, and more recently from the cloning of a gene encoding a G-protein-coupled receptor for cannabinoids. This receptor is expressed in the brain but not in the periphery, except for a low level in testes. It has been proposed that the nonpsychoactive effects of cannabinoids are either mediated centrally or through direct interaction with other, non-receptor proteins. Here we report the cloning of a receptor for cannabinoids that is not expressed in the brain but rather in macrophages in the marginal zone of spleen.

Amides↗
PubMed1993

Carbon abundance and silicate mineralogy of anhydrous interplanetary dust particles.

We have studied nineteen anhydrous chondritic interplanetary dust particles (IDPs) using analytical electron microscopy. We have determined a method for quantitative light element EDX analysis of small particles and have applied these techniques to a group of IDPs. Our results show that some IDPs have significantly higher bulk carbon abundances than do carbonaceous chondrites. We have also identified a relationship between carbon abundance and silicate mineralogy in our set of anhydrous IDPs. In general, these particles are dominated by pyroxene, olivine, or a subequal mixture of olivine and pyroxene. The pyroxene-dominated IDPs have a higher carbon abundance than those dominated by olivines. Members of the mixed mineralogy IDPs can be grouped with either the pyroxene- or olivine-dominated particles based on their carbon abundance. The high carbon, pyroxene-dominated particles have primitive mineralogies and bulk compositions which show strong similarities to cometary dust particles. We believe that the lower carbon, olivine-dominated IDPs are probably derived from asteroids. Based on carbon abundances, the mixed-mineralogy group represents particles derived from either comets or asteroids. We believe that the high carbon, pyroxene-rich anhydrous IDPs are the best candidates for cometary dust.

Astronomy↗
PubMed1993

c-jun expression in substantia nigra neurons following striatal 6-hydroxydopamine lesions in the rat.

The proto-oncogene c-jun is thought to play a role in the control of growth and differentiation of many cell types. It has been demonstrated previously that damage to axons of peripheral motor or sensory neurons resulted within 24 h in substantially increased levels of the c-jun gene in the parent cell bodies. These increased levels of c-jun protein and messenger RNA are maintained if the damaged nerve is ligated, but return to basal levels if the peripheral nerve is allowed to regenerate. We have examined the expression of immediate early genes in central neurons of the rat and now show that a 6-hydroxydopamine-induced axotomy of the dopaminergic nigrostriatal pathway results in a substantial increase in the levels of c-jun (but not c-fos) messenger RNA and protein within neurons of the substantia nigra pars compacta. However, the central neuronal response differs from the peripheral nerve response in that it becomes maximal at four to eight days post-lesion and is transient, declining to control levels in nigral neurons by 14 days post-lesion. These expression patterns may be related to the differential capacity of central and peripheral neurons to regenerate. The precise role of c-jun in these processes, or in the regenerative response, is unclear but it remains possible that c-jun activation following axon damage leads to an increased expression of genes which are essential for the regenerative response. The nature of the mechanism by which c-jun levels are attenuated in central neurons is also unclear, but inhibitory factors, generated by the central environment, may play a role.

Animals↗
PubMed1993

The regional distribution of extracellularly regulated kinase-1 and -2 messenger RNA in the adult rat central nervous system.

It has previously been shown that an intracellular serine/threonine kinase known as extracellularly signal-regulated kinase, also known as microtubule-associated protein kinase, is phosphorylated and activated in response to a range of hormones, growth factors (e.g. nerve growth factor) and neurotransmitters (e.g. N-methyl-D-aspartate) in a variety of cells including neurons. Extracellularly regulated kinases phosphorylate transcription factors, cytoskeletal proteins and enzyme targets. As such they are believed to function in neuronal signal transduction. In situ hybridization histochemistry using synthetic oligonucleotide probes has been used to identify cells in the adult rat central nervous system containing messenger RNAs coding for two isoforms of extracellularly regulated kinase. Extracellularly regulated kinase-2 messenger RNA was observed in many regions including the cerebral cortex, olfactory bulb, hippocampus, amygdala, basal ganglia (except the globus pallidus and endopeduncular nucleus), basal nucleus, thalamus, hypothalamus, brain stem nuclei, cerebellum and neurons in the spinal cord. Extracellularly regulated kinase-1 messenger RNA was confined to fewer regions than extracellularly regulated kinase-2 messenger RNA. Hybridization signals for extracellularly regulated kinase-1 were seen in the olfactory bulb, cortex, regions of the hippocampus, amygdala, nucleus basalis of Maynert, substantia nigra, some hypothalamic and brainstem nuclei and cerebellum, as well as neurons of the spinal cord. Of particular interest, extracellularly regulated kinase-1 messenger RNA was absent from all regions of the basal ganglia and thalamus. Furthermore, extracellularly regulated kinase-1 was almost absent from the CA1 region, whereas extracellularly regulated kinase-2 was present in all neurons of the hippocampus. There were no CNS regions that expressed extracellularly regulated kinase-1 but not extracellularly regulated kinase-2; however, neurons of the dorsal root ganglia showed extracellularly regulated kinase-1 but not extracellularly regulated kinase-2 messenger RNA. Although extracellularly regulated kinase-1 and extracellularly regulated kinase-2 expression was selectively neuronal in the brain, extracellularly regulated kinase-1 messenger RNA was localized to glia in the spinal cord. The distinct cellular distribution of individual extracellularly regulated kinases in the adult rat CNS suggests that they play unique signalling roles.

Animals↗
PubMed1992

Dissociation of the striatal D-2 dopamine receptor from adenylyl cyclase following 6-hydroxydopamine-induced denervation.

Intracellular cyclic AMP accumulation following exposure to dopamine (DA) agonists and and antagonists was measured in striatal slices from rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway and which showed contralateral circling to apomorphine. Both DA (10-320 microM) and the D-1 agonist SKF 38393 (0.1-32 microM) increased cyclic AMP accumulation in striatal slices from the lesioned and intact hemispheres. The EC50 for DA to increase cyclic AMP accumulation in slices was greater in the 6-OHDA-lesioned striata compared to the intact striatum, but the EC50 for SKF 38393 was not affected. The D-1 antagonist SCH 23390 (10 microM) completely inhibited the ability of DA and SKF 38393 to increase cyclic AMP accumulation in striatal slices from both denervated and intact sides of the brain. In slices from the intact hemisphere the increase in DA-induced cyclic AMP accumulation was enhanced by the D-2 antagonist (+/-)-sulpiride (50 microM) but (+/-)-sulpiride had no effect on the DA response in slices from the lesioned side. Similarly, the ability of SKF 38393 to enhance cyclic AMP accumulation was blocked by the D-2 agonist quinpirole (10 microM) in striatal slices from the intact hemisphere but not in tissue from the lesioned side. The density of striatal D-1 and D-2 receptors assessed by [3H]SCH 23390 and [3H]spiperone binding did not differ between the hemispheres although there was an increase in the affinity of D-1 receptors for [3H]SCH 23390 in the lesioned striatum. After striatal deafferentiation there appears to be an uncoupling of the "inhibitory" D-2 receptor from the D-1 receptor-associated adenylyl cyclase.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Acute reserpine treatment induces down regulation of D-1 dopamine receptor associated adenylyl cyclase activity in rat striatum.

Behavioural studies suggest a functional interaction between D-1 and D-2 systems in normal rat striatum to alter motor behaviour and which is disrupted by dopamine depletion induced by acute reserpine treatment. Consequently, we have investigated the effect of acute reserpine treatment on the biochemical interaction between D-1 and D-2 receptors present in rat striatal slices. Twenty-four hours following the administration of reserpine (5 mg/kg i.p.), striatal dopamine content was depleted by more than 73%; the density (B(max)) of D-1 receptor sites measured by the in vitro binding of [3H]SCH 23390 to striatal membranes was increased while the binding of [3H]spiperone to D-2 receptor sites was unaltered. Reserpine treatment had no effect on the affinity (Kd) of [3H]SCH 23390 or [3H]spiperone for D-1 and D-2 sites. Basal levels of cyclic AMP accumulation in striatal slices prepared from reserpine-treated rats were lower than those observed in control slices. In striatal slices prepared from normal rats, dopamine (10-320 microM) and the D-1 agonist SKF 38393 (0.1-3.2 microM) induced concentration-dependent increases in cyclic AMP accumulation. The D-1 antagonist SCH 23390 (10 microM) abolished the accumulation of cyclic AMP produced by dopamine or SKF 38393. The D-2 antagonist (+/-)-sulpiride (50 microM) enhanced the response to dopamine (10-320 microM) while the D-2 agonist quinpirole (10 microM) abolished the response to SKF 38393 (0.1-3.2 microM). However, 24 hr after reserpine treatment the ability of dopamine (10-320 microM) and SKF 38393 (0.1-3.2 microM) to elicit an increase in cyclic AMP accumulation was markedly reduced in striatal slices. SCH 23390 (10 microM) did not enhance the trend for an increase in cyclic AMP accumulation produced by dopamine. Also, quinpirole (10 microM) did not affect the response to SKF 38393 (0.1-3.2 microM) in striatal slices from reserpine pretreated rats. The data confirm the positive linkage between D-1 receptors and adenylyl cyclase and the inhibitory coupling to D-2 sites in striatal slices from normal, rats. Acute reserpine treatment appears to cause an uncoupling of D-1 receptors associated with adenylyl cyclase.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Vascular response to fractionated irradiation in the rat lung.

The effects of fractionated hemithorax irradiation on normal lung tissue were examined by measuring changes in the vascular permeability surface area product (PS) and relative lung blood flow in Sprague-Dawley rats. The rats received five daily fractions per week of either 3.0 or 4.0 Gy for 4 weeks to the left lung. Between 3 and 5 weeks after the start of irradiation, the average PS was approximately 50% above normal for the group of rats that received 3.0 Gy/day and 200-300% above normal in the group of rats that received 4.0 Gy/day. Treatment with cyproheptadine, indomethacin, or theophylline had no effect, but treatment with dexamethasone significantly reduced PS to near normal levels. Left-to-right blood flow ratios in the group of rats that received 3.0 Gy/day decreased to 66% of normal levels by 4 weeks. In the group of rats that received 4.0 Gy/day, blood flow decreased to 46% of normal levels by 4 weeks. Treatment with dexamethasone maintained normal blood flow until the drug dose was reduced. These results agree with earlier studies using single-dose irradiation and indicate that the methods used to measure PS and blood flow are sensitive at low doses.

Animals↗
PubMed1989

Substance P induced hydrolysis of inositol phospholipids in rat skin in an in vivo model of inflammation.

The present study was undertaken to study the ability of substance P (SP) to induce inositol phospholipid (IP) hydrolysis measured as inositol mono-phosphate (IP1) accumulation, in an in vivo blister model of neurogenic inflammation in the rat hind footpad. SP was found to induce IP1 accumulation in a concentration dependent manner. The use of SP analogues (SP5-11 and SP1-7) indicated that the response is mainly mediated by the C-terminal sequence of the peptide. The response was significantly reduced by the SP antagonist spantide, suggesting that the response is mostly due to activation of the SP receptor on small diameter vessels. Capsaicin pretreatment did not have an effect on the ability of SP to induce the response. Experiments with mepyramine suggest that the response is also partly mediated by SP induced histamine release from mast cells. This is the first study to provide direct evidence for phosphoinositide mediated SP effects in the skin.

Animals↗
PubMed1989

NK-1 receptor mediation of neurogenic plasma extravasation in rat skin.

1. Plasma extravasation was induced by electrical nerve stimulation and by perfusion of tachykinins over a vacuum-induced blister base on rat footpad. 2. Stimulation of the sciatic nerve (18 V, 15 Hz, 0.5 ms) for 20 min produced a significant increase in the protein content of the perfusate. The response in capsaicin pretreated rats was only 4% of the control response. This indicates that the electrically-induced plasma extravasation response was mediated by capsaicin-sensitive sensory fibres. 3. Exogenous perfusion of the mammalian tachykinins substance P, neurokinin A and neurokinin B and the non-mammalian tachykinins physalaemin, kassinin and eledoisin was used to determine the tachykinin receptor type mediating the plasma extravasation response. Dose-response curves of the tachykinins (10(-9) M-10(-4) M) gave a rank order of potency of substance P = physalaemin greater than eledoisin greater than or equal to kassinin greater than neurokinin B = neurokinin A. 4. In addition, specific agonists of neurokinin receptors were perfused. Perfusion of [Glp6, D-Pro9] SP6-11 and [Glp6, L-Pro9]SP6-11 demonstrated that the L-Pro isomer was much more potent than the D-Pro isomer. 5. The rank order of potency and the greater potency of [Glp6, L-Pro9]SP6-11 over its D-isomer indicate an NK-1 neurokinin receptor mediates plasma extravasation in rat footpad skin.

Animals↗
PubMed1982

A microcomputer system for the collection and analysis of antibiotic sensitivity test data.

A microcomputer system for the routine collection and analysis of microbiological data is described. A digitising tablet is used as a method of data input. A series of analysis programmes was developed to allow investigation of the distribution of organisms in relation to the type of specimen in which they occur, the origin of the specimen and also to examine their associated sensitivity patterns. In this instance a Commodore PET was used, though other microcomputers could be similarly employed with equal facility.

Anti-Bacterial Agents↗