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G H Jones

Publications and source records attributed to G H Jones.

At least 55 records · Page 3Linked to original sources
PubMed1994

Activation of phenoxazinone synthase expression in Streptomyces lividans: characterization of the activator fragment from Streptomyces antibioticus.

We have isolated an active 719 bp fragment from the 4.3 kb region of the genome of Streptomyces antibioticus that activates a silent phenoxazinone synthase (PHS) gene in Streptomyces lividans. Sequencing of the 719 bp fragment revealed several potential open reading frames (ORFs); however, the distribution of G + C in these putative ORFs was uncharacteristic of streptomycete genes. No RNA products transcribed from the active sequence were detected by dot-blot hybridization and no proteins corresponding in size to the predicted products from the ORFs were observed when appropriate plasmids were used as templates in a streptomycete coupled transcription-translation system. Fragments of 249 and 243 bp, respectively, were obtained from the 719 bp fragment from S. antibioticus and from the S. lividans genome by PCR cloning. Both fragments activated phs in S. lividans when cloned on a high copy number plasmid.

Base Sequence↗
PubMed1994

Purification and properties of ATP:GTP 3'-pyrophosphotransferase (guanosine pentaphosphate synthetase) from Streptomyces antibioticus.

Two forms of ATP:GTP 3'-pyrophosphotransferase (guanosine pentaphosphate synthetase) have been purified from Streptomyces antibioticus. The larger form has an M(r) of 88,000, while the M(r) of a smaller form is 47,000. Both synthetase forms are active in the formation of guanosine 5'-triphosphate, 3'-diphosphate in reaction mixtures containing methanol. Unlike the RelA protein from Escherichia coli, the synthetases from S. antibioticus do not use GDP efficiently as a substrate. Experiments using crude extracts of S. antibioticus mycelium and the 88,000-M(r) form of guanosine pentaphosphate synthetase strongly suggest that the 47,000-M(r) species is produced by proteolysis of the larger species. This conclusion is supported by the observation that antibody to either protein reacts with the other protein. Thus, the 88,000-M(r) species may be the catalytically relevant protein in vivo. Unlike the RelA protein, the 88,000-M(r) protein is not activated by ribosomes. Modest levels of guanosine pentaphosphate synthesis were observed in mycelial extracts derived from nine other actinomycetes.

Chromatography, DEAE-Cellulose↗
PubMed1994

Activation of ATP:GTP 3'-pyrophosphotransferase (guanosine pentaphosphate synthetase) in Streptomyces antibioticus.

The activity of the ATP:GTP 3'-pyrophosphotransferase (guanosine pentaphosphate synthetase I [GPSI]) from Streptomyces antibioticus is stimulated maximally by methanol at 20% (vol/vol) in assay mixtures. Although the enzyme is not activated by ribosomes, its activity is stimulated by tRNA (uncharged or charged) and by synthetic mRNA [e.g., poly(U)]. The level of stimulation is greater in the presence of tRNA and poly(U) together than with either RNA alone. Incubation of GPSI with low levels of trypsin also leads to activation of the enzyme. Analysis of the products of mild trypsin digestion revealed the presence of two intermediates whose M(r)s are identical to those of species produced by incubation of purified GPSI with crude extracts of S. antibioticus mycelium. GPSI can be activated by incubation with crude mycelial extracts, and this activation is partially inhibited by the inclusion of trypsin inhibitor in reaction mixtures.

Amino Acyl-tRNA Synthetases↗
PubMed1994

Schizophrenic psychosis and associated aqueduct stenosis.

In two adults, both schizophrenia and hydrocephalus were associated with aqueduct stenosis. The prevalence is argued to be above chance, and may contribute to the neurodevelopmental hypothesis of the causality of schizophrenia.

Adult↗
PubMed1993

Combined purification of actinomycin synthetase I and 3-hydroxyanthranilic acid 4-methyltransferase from Streptomyces antibioticus.

Actinomycin synthetase I, which activates the precursor of the chromophore of actinomycin, has been purified nearly 1000-fold from extracts of Streptomyces antibioticus. The enzyme has an M(r) of 45,000 and appears to function as a single polypeptide chain. The formation of the enzyme is repressed when S. antibioticus mycelium is grown on glucose as a carbon source. Several benzoic acid derivatives, including intermediates in the putative pathway for actinomycin biosynthesis, were capable of supporting ATP-pyrophosphate exchange catalyzed by actinomycin synthetase I. Interestingly, three synthetic phenoxaziones also functioned as substrates in the exchange reaction. It proved possible to purify a second enzyme involved in actinomycin biosynthesis, 3-hydroxyanthranilic acid 4-methyltransferase, from the same extracts prepared for the purification of actinomycin synthetase I and by similar procedures. Streptomyces lividans, previously shown to contain a silent gene for the enzyme phenoxazione synthase, apparently does not contain a silent pathway for the complete synthesis of actinomycin since neither actinomycin synthetase I nor the methyltransferase could be detected in strains containing a cloned sequence that activates phenoxazione synthase expression.

Electrophoresis, Polyacrylamide Gel↗
PubMed1993

Synaptonemal complex karyotyping: an appraisal based on a study of Crepis capillaris.

A synaptonemal complex (SC) karyotype for Crepis capillaris, based on SC measurements from 92 surface-spread pachytene nuclei, was compared with the mitotic karyotype of this species in order to evaluate the specific and general validity of SC karyotyping and to assess its potential for high resolution physical mapping. Although there are obvious similarities between the SC and mitotic karyotypes of Crepis capillaris, detailed quantitative comparisons reveal that they differ in some respects, both with regard to the relative lengths of entire chromosomes and arm ratios. The arm ratio differences between SC and mitotic chromosomes are evident in both the A and C chromosomes and reflect the distribution of C-banding heterochromatin. Based on this comparison, heterochromatin appears to be underrepresented in SC length. However, the relative lengths of entire A and C chromosome SCs do not conform to this model and suggest that some other factor or factors are also influencing SC lengths differentially. It is concluded that the non-agreement of SC and mitotic karyotypes does not invalidate the use of SCs for karyotyping and physical mapping purposes provided that any differences are understood and characterized as far as possible.

Karyotyping↗
PubMed1993

Contrasting effects of the competitive NMDA antagonist CPP and the non-competitive NMDA antagonist MK 801 on performance of an operant delayed matching to position task in rats.

The effects of the competitive NMDA antagonist CPP and the non-competitive NMDA antagonist MK 801 (dizolcipine) on short term working memory in the rat were investigated. The behavioural paradigm used was discrete trial, operant delayed matching to position, as originally described by Dunnett (1985), with delays of 0, 5, 15 and 30 s. These delays generated an orderly "forgetting" curve in control rats, with matching accuracy decreasing from approximately 100% at 0-s delay to approximately 75% at 30-s delay. Intraperitoneal (IP) administration of CPP (10 mg/kg) produced a marked delay dependent impairment in performance, suggesting a specific effect on short term working memory. This effect was accompanied by a minor decrease in the speed of responding, and a slight increase in the number of missed trials. Lower doses of CPP had no significant effects on either matching accuracy or sedation. In contrast, IP administration of MK 801 (0.1 and 0.2 mg/kg) caused a marked delay independent impairment in the accuracy of delayed matching performance, suggesting a non-specific disruption of performance. A lower dose (0.05 mg/kg) of MK 801 had no significant effect on matching accuracy. The two lower doses of MK 801 increased the number of nose pokes made during the delays and tended to increase the speed of responding, suggesting a stimulant-like action. The highest dose of MK 801 had the opposite effects and also decreased the number of trials completed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Environmental and pharmacological sensitization: effects of repeated administration of systemic or intra-nucleus accumbens cocaine.

The effects of repeated systemic or intra-nucleus accumbens cocaine administration on locomotor activity were examined for environmental dependence. Repeated IP administration of cocaine (15 mg/kg) for 5 days in the context of a given environment increased the locomotor response to a subsequent IP cocaine challenge in that environment. However, there were no differences in the locomotor response to a subsequent IP cocaine challenge in the test chamber in subjects which had received prior repeated IP administration of cocaine in the home-cage. In a second experiment, cocaine (100 micrograms/side) was infused into the nucleus accumbens (NACC) daily for 5 days. This repeated administration produced increases in locomotor activity to subsequent intra-NACC cocaine infusions that were environmentally independent. In contrast to the effects of repeated IP cocaine administration, subjects which received administration of vehicle, acute cocaine, or repeated cocaine in the NACC did not differ following an IP cocaine challenge. The results from these experiments indicate that increases in the response to IP cocaine following repeated IP administration are in part environmentally dependent. Moreover, repeated intra-NACC cocaine infusions increase the responsiveness of the NACC to subsequent intra-NACC cocaine. However, local activation of the NACC alone does not appear to be adequate to produce sensitization to systemically administered cocaine.

Animals↗
PubMed1992

6-Hydroxydopamine lesions of the medial prefrontal cortex fail to influence cocaine-induced place conditioning.

This study investigated the involvement of medial prefrontal cortex (mPFC) dopamine in cocaine place conditioning using a totally balanced place conditioning design. Presynaptic dopamine terminals of the mPFC were lesioned by bilaterally infusing the selective neurotoxin 6-hydroxydopamine (6-OHDA). These lesions significantly depleted dopamine (-83%) and norepinephrine (-70%) in the mPFC but there were no significant reductions in either the nucleus accumbens or in the caudate-putamen compared with sham-operated controls. Furthermore, serotonin levels were not affected in any of the brain regions investigated. These lesions failed to attenuate place conditioning induced by the intraperitoneal (i.p. 10 mg/kg) administration of cocaine when compared to sham lesioned controls. In addition, there were no significant differences in spontaneous locomotor activity between the two groups during the preconditioning phase or the test phase. These results suggest that 6-OHDA lesions which produced profound depletions of dopamine and norepinephrine in the mPFC did not alter the rewarding efficacy of cocaine as measured by the place conditioning paradigm.

Animals↗
PubMed1992

Social isolation increases the density of [125I]omega-conotoxin GVIA binding sites in the rat frontal cortex and caudate nucleus.

Rats were reared from weaning either in isolation or in social groups for 12 weeks. Potential isolation-related changes in L- and N-type voltage-sensitive calcium channels (VSCCs) were assessed by the in vitro binding of [3H]isradipine (100 pM) and [125I]omega-conotoxin GVIA (4 pM) to membranes prepared from three discrete central nervous system regions: frontal cortex, caudate nucleus and hippocampus. The [3H]isradipine binding was generally not affected by isolation. However, [125I]omega-conotoxin GVIA binding was significantly higher in frontal cortex (52%) and caudate nucleus (75%) of isolated rats when compared with socially reared controls. The increased [125I]omega-conotoxin GVIA binding reflected an elevated density of binding sites without an alteration of receptor affinity. The possible contribution of an increased density of neuronal N-VSCCs (as labeled with [125I]omega-conotoxin GVIA) to the behavioral and neurochemical changes observed in 'isolation syndrome' is discussed.

Animals↗
PubMed1992

Conditioned locomotor activity but not conditioned place preference following intra-accumbens infusions of cocaine.

In the first experiment, the conditioned place preference (CPP) paradigm was used to examine the rewarding properties of bilateral microinfusions of cocaine HCl into the nucleus accumbens (0, 12.5, 25, 50, or 100 micrograms). No dose of intra-accumbens cocaine induced a significant CPP. However, bilateral intra-accumbens infusions of d-amphetamine sulfate (10 micrograms) or intraperitoneal administration of cocaine HCl (5 or 10 mg/kg) both produced a significant preference for the drug-paired compartment. In the second experiment, the ability of bilateral intra-accumbens infusions of cocaine HCl (50 micrograms) to elicit conditioned locomotor activity (CLA) was examined. During the conditioning trials, intra-accumbens cocaine significantly increased locomotor activity. On the test day, when no drug was administered, the group that had previously received cocaine in the activity chamber showed significantly greater locomotor activity than the vehicle control group. This demonstration of CLA indicates that rats are able to associate the effects of intra-accumbens infusions of cocaine with environmental stimuli; however, these infusions are not rewarding as measured by the CPP paradigm. In addition, these results may indicate important differences between the neural substrates for cocaine and amphetamine reward and reveal a dissociation between CPP and CLA.

Amphetamine↗
PubMed1992

Individual differences in amphetamine sensitization: dose-dependent effects.

Rats were screened for locomotor activity in a novel environment and divided into high (HR) or low (LR) responders based on whether their locomotor score for the first hour was above or below the median. In the first experiment, HR and LR rats were compared for their locomotor response following repeated administration of either 0.0, 0.5, 1.0, or 1.5 mg/kg d-amphetamine sulfate (AMPH). Injections of either 0.5 or 1.0 mg/kg AMPH produced higher locomotor activity in HR rats than in LR rats. Furthermore, there was a correlation between the locomotor response to novelty and the response to either 0.5 or 1.0 mg/kg AMPH. In addition, whereas both groups of rats developed the same degree of sensitization to 0.5 mg/kg AMPH, only the HR rats developed pronounced sensitization to repeated administration of 1.0 mg/kg AMPH. When both HR and LR were considered, there was a significant correlation between response to novelty and the extent of sensitization to the locomotor-stimulating properties of 1.0 mg/kg AMPH. There were no differences in locomotor activity or sensitization between HR and LR rats following the highest dose of AMPH (1.5 mg/kg). In a separate experiment, HR and LR rats were compared for locomotor activity following a series of intracranial infusions of AMPH. There were no overall differences in locomotor activity between the HR and LR groups following AMPH infusions into either the nucleus accumbens (NACC) or the anterior dorsal striatum (ADS). However, the locomotor activity scores in the novel environment significantly correlated with the locomotor response to 3.0 micrograms AMPH infused into either the NACC or ADS.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1992

Sensitization and individual differences to IP amphetamine, cocaine, or caffeine following repeated intracranial amphetamine infusions.

Rats that have a high locomotor response to novelty (HR) sensitize more readily to IP-administered amphetamine than rats with a low locomotor response (LR) to novelty. This experiment compared sensitization in HR and LR rats following amphetamine (3.0 micrograms/side for 5 days) infused bilaterally into either the nucleus accumbens (NACC), ventral tegmental area (VTA), or the medial frontal cortex (MFC). The subsequent locomotor response to IP-administered d-amphetamine sulfate (1 mg/kg), cocaine HCl (15 mg/kg), and caffeine benzoate (20 mg/kg) was also examined. No differences were observed between HR and LR rats following amphetamine infusion into either the MFC, NACC, or VTA. However, HR rats showed greater locomotor activity compared to LR rats following either IP amphetamine, cocaine, or caffeine for subjects cannulated in the NACC, MFC, or the VTA. Repeated infusions of amphetamine into the VTA increased the locomotor response to both IP amphetamine and cocaine, but not to IP caffeine, while repeated infusions of amphetamine into the NACC or MFC had no effect on locomotor response to any drug subsequently administered IP. The results support previous findings that changes induced by intra-VTA infusions, but not intra-NACC or MFC infusions, of amphetamine induce sensitization to IP-administered amphetamine and cocaine. Findings from the present experiment indicate the ability of the dopamine cell body region, but not the dopamine terminal fields, to produce locomotor sensitization to amphetamine and cocaine. The results from the present experiment also indicate the lack of localization to one of studied regions of individual differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1992

Differential effects of mesocortical, mesolimbic, and mesostriatal dopamine depletion on spontaneous, conditioned, and drug-induced locomotor activity.

Groups of rats with 6-hydroxydopamine (6-OHDA) lesions of either the medial prefrontal cortex (PFC), nucleus accumbens (NAC), or caudate putamen (CPu) were given daily tests for locomotor activity in photocell cages while food deprived. Two separate groups of NAC-lesioned rats were prepared with either large [NACT (90% NAC dopamine depletion)] or partial [NACP (67% NAC dopamine depletion)] lesions. NACT rats were spontaneously hypoactive whereas NACP rats were hyperactive compared with sham-operated controls. PFC-lesioned rats were also hyperactive compared to their respective controls. Spontaneous locomotor activity in CPu-lesioned rats did not differ from shams. When daily food supplements were paired with the photocell cages, all subjects developed a conditioned locomotor response. During the first few days of conditioning, the response to this conditioning procedure was markedly greater in the NACP group whereas the response in the NACT group was unaffected initially and actually enhanced during the latter days of testing. The locomotor response to the conditioning procedure was unaffected in either the PFC- or CPu-lesioned groups. Both the NACT and NACP lesions attenuated the locomotor response to 1.5 mg/kg d-amphetamine sulphate IP, and the NACT group showed a supersensitive response to 0.1 mg/kg apomorphine HCl SC. PFC or CPu 6-OHDA lesions did not alter the response to either drug. These results differentiate the role of PFC, NAC, and CPu dopamine in spontaneous, conditioned, and drug-induced locomotor activity and further implicate dopaminergic mechanisms of the NAC in the magnitude of the behavioural response to incentive stimuli.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in vivo neurochemistry.

This series of experiments compared isolation-reared and socially reared rats for their locomotor activity, behavioural stereotypy, and monoamine function both postmortem and in vivo using intracerebral dialysis. In Experiment 1, isolates showed an altered time course of locomotor activity following d-amphetamine sulphate (AMPH) administration (0.5, 2.0, 3.0, or 5.0 mg/kg, SC). Isolation-reared rats also showed increased sensitivity to the sedative effects of a low dose of apomorphine hydrochloride (0.1 mg/kg) but did not differ from social controls following higher doses of the drug (0.5, 1.5, or 3.0 mg/kg, SC). Isolates showed a decrease in the intensity of apomorphine-induced stereotyped behaviours but no change in stereotypy induced by AMPH. In Experiment 2, isolates had higher postmortem dopamine (DA) concentrations and an altered asymmetry in DA function in the medial prefrontal cortex (PFC) but not in the nucleus accumbens (NAC) or caudate putamen (CPu). Isolated rats also had a lower 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the NAC (but not in the PFC or CPu) compared to controls. Experiment 3 used intracerebral dialysis to examine monoamine function in vivo following isolation rearing. Isolates showed greater increases in extracellular DA and greater decreases in DOPAC in response to 2 mg/kg AMPH SC in both the NAC and CPu. There were no apparent differences in the perfusate concentrations of either dopamine (DA), dihydroxyphenylacetic acid (DOPAC), or homovanillic acid (HVA) prior to drug administration. However, consistent with the results of Experiment 2, isolates had a reduced basal perfusate concentration of 5-HIAA from the NAC but not from the CPu. Experiment 4 measured postsynaptic DA function in CPu tissue slices following isolation. Isolation rearing did not affect cAMP accumulation in response to stimulation of D1 DA receptors by DA (0, 2.7, 9, or 30 microM). In addition, isolation rearing did not affect the coupling between D1 and D2 receptors, as measured by the increase in cAMP accumulation with 1 microM 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepin (SK&F 38393) and its reduction by 10 microM quinperole hydrochloride (LY 171555). These results are discussed in terms of the possible relationship between these neurochemical findings and the behavioural disturbances following isolation rearing of rats.

3,4-Dihydroxyphenylacetic Acid↗