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Biomedical subjects

G H Jones

Publications and source records attributed to G H Jones.

At least 91 records · Page 5Linked to original sources
PubMed1989

Effects of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on visual discrimination acquisition, performance and reversal in the rat.

Rats received infusions of ibotenic acid into the substantia innominata, in the region of the nucleus basalis of Meynert (nbM), before and after training on simple (simultaneous) and conditional visual discriminations. The ibotenate infusions reduced cortical choline acetyltransferase (ChAT) levels by about 20%, destroyed many ChAT-immunoreactive neurons in the nbM, but also caused the loss of many neurons in the substantia innominata and adjacent areas. These lesions did not impair the acquisition and performance of a simple visual discrimination, but did impair reversal of the discrimination and the performance of a conditional visual discrimination. However, the degree of impairment was unrelated to the degree of cortical ChAT loss. Ibotenic acid lesions to the dorsal globus pallidus also impaired reversal of discrimination but left acquisition and performance unaffected. Striatal dopamine depletion produced by 6-hydroxydopamine (6-OHDA) infusions into the mid-ventral caudate nucleus impaired performance of the simultaneous visual discrimination. Cortical noradrenaline depletion produced by 6-OHDA lesions of the dorsal noradrenergic bundle either alone or in combination with ibotenic acid lesions of the substantia innominata had no effect on acquisition of the discrimination. It is concluded that ibotenic acid lesions of the substantia innominata or to the dorsal globus pallidus affect learning and performance of conditional visual discrimination performance and impair reversal learning without affecting the capacity to discriminate visual events. These results are compared to those following cortical noradrenaline depletion or striatal dopamine loss.

Animals↗
PubMed1989

Isolation-rearing retards the acquisition of schedule-induced polydipsia in rats.

Rats were reared from weaning either in isolation or in social groups for 10 weeks and were then tested for the acquisition of schedule-induced polydipsia (SIP). Isolation-reared rats were impaired in the development of this behaviour when compared to socially-reared controls. This reduction in drinking was specific to this test situation. Home cage water consumption and drinking in the SIP test chamber without a schedule of food delivery were unaltered and home cage drinking following water deprivation was significantly higher in the isolates. Housing adult rats in isolation did not impair SIP. The locomotor hyperactivity induced by isolation was also specific to rearing conditions. The inverse relationship between water consumption on the last day of testing and plasma corticosterone levels observed in both the socially-reared and socially-housed rats was absent in both the isolation-reared and isolation-housed rats.

Animals↗
PubMed1989

Effects of unilateral dorsal and ventral striatal dopamine depletion on visual neglect in the rat: a neural and behavioural analysis.

Rats were trained in a specially designed apparatus to detect brief, unpredictable visual stimuli presented to either side of the head. In one condition, rats reported the detection of the visual stimulus by removing their heads from a central location and responding in one of two adjacent side-holes where the visual stimulus had occurred. In the other condition, rats were trained to respond in the hole on the opposite side to where the visual stimulus had occurred. Following training all rats received striatal infusions of 6-hydroxydopamine leading to profound striatal dopamine depletion. One group received unilateral intra-nucleus accumbens 6-hydroxydopamine infusions. Two groups received 6-hydroxydopamine unilaterally into the caudate nucleus. Two other groups received two infusions of 6-hydroxydopamine, intra-accumbens and intra-caudate, on either the same side or on opposite sides. The results showed that all groups, except that receiving only intra-accumbens 6-hydroxydopamine, exhibited a significant bias in responding towards the side of the lesion which correlated with dopamine depletion in the head of the caudate nucleus, regardless of the type of discrimination or pre-operative strategy. These biased groups were also slower to initiate, but not to complete, contralateral responses. Detailed analysis of the behavioural evidence suggested that unilateral striatal dopamine depletion does not produce sensory loss or sensory inattention but rather an output type neglect, perhaps related to hemiakinesia or "intentional neglect". The bias recovered to preoperative levels by 7 weeks after surgery, but could be reinstated by pretreatment with alpha-methyl-para-tyrosine, thus suggesting the involvement of presynaptic mechanisms in recovery. Although unilateral dopamine depletion from the nucleus accumbens alone had no effects on visual neglect, it produced a lateralized bias in premature responding away from the side of the lesion, contrasting with the bias towards the side of the lesion seen in all of the other groups. These effects appeared to summate in this and in another condition in which a more eccentric response was required for stimulus detection, to suggest an interaction in function between the dorsal and ventral striatum.

Animals↗
PubMed1989

Comparative effects of quisqualic and ibotenic acid-induced lesions of the substantia innominata and globus pallidus on the acquisition of a conditional visual discrimination: differential effects on cholinergic mechanisms.

Two experiments tested the hypothesis that the deficits in conditional discrimination learning produced by ibotenic acid-induced lesions of the ventral pallidum and substantia innominata are produced by loss of the magnocellular cholinergic cells in the nucleus basalis and adjacent regions. Experiment 1 replicated the previously reported deficit in conditional learning produced by ibotenate-induced lesions of the ventral pallidum/substantia innominata, but failed to demonstrate any restoration of learning by a subchronic regimen of the acetylcholinesterase inhibitor physostigmine sufficient to produce significant (30%), but equivalent, degrees of inhibition in the frontal cortex of ventral pallidum/substantia innominata-lesioned or sham-operated rats. Experiment 2 examined the effects of quisqualic acid-induced lesions of the ventral pallidum/substantia innominata. According to most of the measures of learning employed, the quisqualic acid-induced lesion of the ventral pallidum/substantia innominata failed to impair conditional learning, even though the quisqualate-induced lesion produced greater degrees of cholinergic neuron destruction than the ibotenate-induced lesion, as measured in terms of reductions in cortical choline acetyltransferase activity (44% vs 27%). Although consideration of individual data suggested that very high (60%) levels of choline acetyltransferase reduction in Experiment 2 might have detrimental effects of conditional learning, the overall failure of the quisqualate-induced lesions of the ventral pallidum/substantia innominata to impair learning is to be contrasted with the significant behavioural effects of ibotenate-induced lesions. Histological and immunocytochemical analysis showed that the quisqualate-induced lesion, unlike that produced by ibotenate, tended to produce less damage to the overlying dorsal globus pallidus and to parvocellular neurons of the ventral pallidum/substantia innominata, thus implicating these nonspecific effects of ibotenate-induced lesions in their behavioural effects. The present results question previous interpretations of the behavioural effects of ibotenate-induced lesions of the ventral pallidum/substantia innominata in terms of damage inflicted on the cortically-projecting cholinergic cells of the nucleus basalis, and suggest that quisqualic acid, although also nonspecific in its excitotoxic effects, is nevertheless more selective for producing damage to cholinergic neurons in the ventral pallidum/substantia innominata than ibotenic acid.

Animals↗
PubMed1989

Attenuation of amphetamine-stereotypy by mesostriatal dopamine depletion enhances plasma corticosterone: implications for stereotypy as a coping response.

The relationship between amphetamine-induced stereotyped behavior and a neuroendocrine index of arousal, plasma corticosterone (CCS), was investigated. 6-Hydroxydopamine lesions of the caudate-putamen, which produced dopamine depletions of 60%, blocked stereotypy and prolonged the elevation in corticosterone associated with d-amphetamine treatment (5 mg/kg). Similar dopamine depleting lesions of the nucleus accumbens, which attenuated the locomotor, but not the stereotypic, response to AMPH did not have this effect on CCS. This pattern of results supports the hypothesis that stereotypy has a coping function which may serve to alter arousal and further suggests important differences between the nigrostriatal and mesolimbic dopamine projections in modulating the responsiveness of the neuroendocrine system. These results have implications for understanding the function of behavioral stereotypies common to a number of psychopathological conditions, including schizophrenia and childhood autism.

Adaptation, Psychological↗
PubMed1989

Meiosis in Mesostoma ehrenbergii ehrenbergii. IV. Recombination nodules in spermatocytes and a test of the correspondence of late recombination nodules and chiasmata.

Male meiosis in Mesostoma ehrenbergii ehrenbergii (2x = 10) is characterized by extreme restriction of chiasma formation; 3 pairs of chromosomes form bivalents at metaphase I which are associated by single very distally localized chiasma, while two pairs of chromosomes remain as unpaired univalents. Electron microscopical three-dimensional reconstruction analysis of serial sections has been applied to 20 pachytene spermatocyte nuclei. In each nucleus three short stretches of synaptonemal complex (SC) were found, confined to a localized branched lobe of the nucleus, confirming the findings of an earlier study. The majority of reconstructed nuclei show that each of the three SC segments has a single prominent recombination nodule ("late" RN) associated with it. Late RNs in this system therefore show an excellent correspondence with metaphase I chiasmata, in contrast to a previous report. M.e. ehrenbergii is therefore not an exception to the hypothesis that meiotic exchange requires a functional late RN. A few nuclei had two, one or no RNs; these presumably represent nuclei that are not at the stage of maximum RN presence. Although M. e. ehrenbergii shows pronounced chiasma localization at the light microscope level, at the ultrastructural level RNs are widely distributed along the 5-10 microns of SC formed in each bivalent, indicating that genetic exchange are not restricted to particular localized sites but occur at a large number of DNA sequence.

Animals↗
PubMed1989

Anterior tumour of the corpus callosum with atypical depression.

We report a patient with an anteriorly placed tumour of the corpus callosum presenting with primarily depressive symptoms, without any associated neurological abnormality. It is important to be alert to the possibility of an organic cause to depression.

Brain Neoplasms↗
PubMed1988

Distribution and some projections of cholinergic neurons in the brain of the common marmoset, Callithrix jacchus.

The distribution of choline acetyltransferase-immunoreactive (ChAT-IR) neurons was studied in the brain of the common marmoset by using immunohistochemistry. ChAT-IR neurons were found in the medial septal nucleus, vertical and horizontal limb nuclei of the diagonal band, the nucleus basalis of Meynert, pedunculopontine nucleus and laterodorsal tegmental nucleus, and also in the striatum, habenula, and brainstem cranial nerve motor nuclei. The organization of ChAT-IR neurons in the basal forebrain, midbrain, and pons is consistent with the Ch1-Ch6 nomenclature introduced by Mesulam et al. ('83). The combination of the retrograde transport of HRP-WGA with ChAT immunohistochemistry revealed the distribution of neurons in the Ch4 cell group projecting to the dorsolateral prefrontal cortex. The activity of ChAT was highest in limbic cortical structures, such as the hippocampus, and lowest in association areas of the neocortex. Lesions at various loci in the basal forebrain resulted in differential patterns of ChAT loss in the cortex, which suggests some degree of topographical organization of Ch4 projections to the cortical mantle.

Animals↗
PubMed1988

Actinomycin synthesis in Streptomyces antibioticus. Purification and properties of a 3-hydroxyanthranilate 4-methyltransferase.

A methyltransferase, which utilizes 3-hydroxyanthranilic acid (HAA) as a substrate, has been purified to near homogeneity from 30-36-h mycelium of the bacterium Streptomyces antibioticus. The enzyme was obtained in approximately 20% yield with a purification of 130-fold. Polyacrylamide gel electrophoresis under denaturing conditions indicates that the enzyme is composed of a single subunit with Mr of about 36,000. On chromatography in 0.5 M NaCl, the enzyme displays a molecular weight of about 37,000. The specific activity of the enzyme in S. antibioticus mycelium is maximal between 30 and 36 h following inoculation of galactose/glutamic acid medium and, at those times post-inoculation, the specific activity is essentially the same in extracts of mycelium obtained from cultures grown on glucose rather than galactose as the carbon source. The enzyme activity is stimulated by Na2EDTA (in crude extracts) and by 2-mercaptoethanol and the methyltransferase shows a strong preference for HAA as substrate as compared with a number of HAA analogs. Thin layer chromatography of ethyl acetate extracts of large-scale incubation mixtures confirms that the product of the reaction is 4-methyl-3-hydroxyanthranilic acid. The reaction product was also a substrate for phenoxazinone synthase and was incorporated into actinomycin by S. antibioticus mycelium. Kinetic parameters for the methyltransferase reaction was determined.

Chromatography, DEAE-Cellulose↗
PubMed1988

Graft-derived recovery from 6-OHDA lesions: specificity of ventral mesencephalic graft tissues.

A series of experiments have been conducted to assess the specificity of recovery from motor asymmetries that is provided by dopamine-rich grafts in the neostriatum of rats with unilateral dopamine-depleting lesions produced by injection of 6-hydroxydopamine into the ascending nigrostriatal pathway. Grafts of embryonic tissue taken from the substantia nigra (rich in dopamine neurons could provide a complete recovery of methamphetamine-induced rotation and a partial recovery of apomorphine-induced rotation, whereas no recovery was seen in rats with grafts of tissue rich in another monoamine (serotonin, dissected from the mesencephalic raphe) or of tissue appropriate to the target (dissected from the striatal eminence). 6-Hydroxydopamine lesions of dopamine cells in the grafts of recovered animals reinstated the initial lesion-induced asymmetry. Dopamine-rich grafts implanted into the intact neostriatum did not induce any "supernormal" asymmetry in the rats, but did provide a "prophylactic" protection against subsequent lesions of the intrinsic ipsilateral dopamine nigrostriatal system. Post-mortem biochemical assays indicated that the extent of dopamine depletion in the neostriatum of lesioned rats correlated highly with both methamphetamine and apomorphine turning rates. Similarly, both drug rotation tests correlated significantly with the extent of dopamine restoration in the dorsal striatum of rats with dopamine-rich grafts, the correlation being significantly higher for the methamphetamine than for the apomorphine test.

Acetylcholinesterase↗
PubMed1988

Effects of diazepam, FG 7142, and RO 15-1788 on schedule-induced polydipsia and the temporal control of behavior.

Although benzodiazepine agonists and inverse agonists have opposite effects on drinking elicited by water deprivation, there is much less information about the effects of these drugs on nonhomeostatic drinking. In this experiment the effects of diazepam (0.3-5.0 mg/kg), a benzodiazepine receptor agonist, and FG 7142 (1.0-9.0 mg/kg), an inverse agonist, were determined on drinking elicited by a FT-60 schedule of food delivery (SIP). Both diazepam and FG 7142 dose-dependently reduced SIP, measured as either licking or volume consumed. In addition, diazepam reduced panel pressing for food, decreased locomotor activity, and changed the time course of each behavior. In contrast, FG 7142 reduced schedule-induced drinking without significantly altering other behaviors. The antagonist RO 15-1788, when given in combination with these drugs, only partially restored the reductions in licking produced by diazepam, but was much more effective in reversing the effects of FG 7142 at doses of the antagonist that failed by themselves to affect responding. The opposite pattern of effects was seen on the volume of water consumed. These effects are discussed in terms of the behavioral and pharmacological specificity of these drugs.

Animals↗
PubMed1988

The relationship between schedule-induced polydipsia and pituitary-adrenal activity: pharmacological and behavioral manipulations.

The relationship between schedule-induced polydipsia (SIP) and pituitary-adrenal activity in rats was investigated using two different approaches that involved either capitalizing on pre-existing individual differences in the propensity to show SIP, or by inducing differences in plasma corticosterone by behavioral or pharmacological means. Thus, in Expt. 1, SIP was monitored after corticosterone levels were pharmacologically altered with drugs that act at the benzodiazepine receptor. In Expt. 2, the relationship between individual differences in water consumption during SIP and plasma corticosterone levels was determined. In addition, corticosterone levels were determined after the prevention of drinking during SIP. Results indicated an inverse relationship between plasma corticosterone levels and SIP. It was also found that corticosterone levels were significantly higher following SIP with water available than after SIP without water. The implications of these results for previous hypotheses of SIP are discussed.

Animals↗
PubMed1988

Topical nonsteroidal antipsoriatic agents. 2. 2,3-(Alkylidenedioxy)naphthalene analogues of lonapalene.

A series of 2,3-(alkylidenedioxy)naphthalene (5a-p) analogues of lonapalene (RS-43179, 1), a 5-lipoxygenase inhibitor currently under clinical investigation for the treatment of psoriasis, has been prepared and evaluated for topical inhibitory activity against arachidonic acid induced mouse ear edema. The results of these studies demonstrate that introduction of the fused 2,3-alkylidenedioxy ring, in place of the acyclic 2,3-dialkoxy substituent pattern characteristic of the previous series, caused a modest dimunition in overall potency within the series. These results suggest a potential steric intolerance for these extended planar analogues, in comparison with their 2,3-dialkoxy predecessors.

Animals↗
PubMed1987

Noradrenaline- and time-dependent changes in neocortical alpha 2- and beta 1-adrenoceptor binding in dorsal noradrenergic bundle-lesioned rats.

A 6-hydroxydopamine-induced lesion of the dorsal noradrenergic bundle (DNB) in rats markedly decreased neocortical noradrenaline concentration (NNC) by 72-100% as measured 1, 3 and 13 months after the lesioning procedure. The concomitant assessment of neocortical alpha 2- and beta 1-adrenoceptor binding (NAAB and NBAB, respectively) usually indicated significant increases of 25-72% for these two variables. There were, however, cases of unchanged NAAB and NBAB which presumably reflected an incomplete DNB lesion and a consequent time-related, partial recovery of NNC. The results emphasize the potential for long-term sequelae of the DNB lesion, and the existence of a critical NNC threshold (approximately 10-30% of control NNC values) which modulates postsynaptic alpha 2- and beta 1-adrenoceptor density.

Animals↗
PubMed1987

Dopamine-rich grafts ameliorate whole body motor asymmetry and sensory neglect but not independent limb use in rats with 6-hydroxydopamine lesions.

The capacity of dopamine (DA)-rich embryonic grafts to influence performance in a skilled motor task has been assessed. In two separate experiments, unilateral 6-hydroxydopamine lesions of forebrain DA systems induced a neglect of the contralateral limb and an almost total preference for use of the ipsilateral limb when reaching through the bars of a cage for food pellets. If the food paw was restrained, either by a bracelet or by injection of a local anaesthetic, the lesioned rats would continue to make many reaching attempts with the contralateral paw, but on the great majority of these attempts they were unsuccessful in grasping or retrieving food. DA-rich grafts, reinnervating the denervated caudate-putamen, provided no detectable benefit to the lesioned rats, neither in reducing the ipsilateral bias in their side preference, nor in increasing their success when constrained to reaching with the contralateral limb. This failure to benefit from the grafts is not due to the grafts themselves not being viable, since the same rats showed substantial compensation of whole body motor asymmetries in spontaneous and drug-induced rotation, and a reduction of asymmetry in a battery of neurological tests of sensorimotor function. The results are discussed in terms of the degree of anatomical integration of the grafts into the host neural circuitry, and the neural organization necessary for the performance of different classes of behavior.

Animals↗
PubMed1987

A decade of lower extremity venous trauma: patency and outcome.

Eighty-two patients with infrailiac venous injuries were reviewed. Veins were repaired in 75 patients and ligated in 7 patients. Clinical outcome could be correlated with anatomic patency for 41 patients who had postoperative venograms. Sixty-three percent of the repairs proved to be patent. Simple repairs were successful more often than complex ones. Site of injury and perioperative therapeutic adjuncts did not affect results. Eleven limbs were amputated, none solely because of venous injury. Edema was present at last follow-up in fewer patients with patent repairs than occluded repairs or ligations. Repair of major lower extremity venous injuries should be attempted routinely in stable patients. Improved patency of complex repairs may require increased use of balloon catheter thrombectomy and other adjunctive procedures. Postoperative venography is very useful for the evaluation of results.

Adolescent↗
PubMed1987

Immuno-enhancing activity of the amino-terminal domain of human prealbumin: isolation, characterization and synthesis.

A decapeptide isolated from highly purified preparations of human prealbumin was able to restore azathioprine (Az) sensitivity, a property of a sub-class of T-lymphocytes, to the spleen rosette-forming cells (RFC) of adult thymectomized (ATx) mice in vitro. The peptide was sequenced by the Edman method and shown to correspond to the ten amino-terminal residues of prealbumin, Gly-Pro-Thr-Gly-Thr-Gly-Glu-Ser-Lys-Cys. Synthesis of this peptide by solid phase methodology confirmed its activity both in vitro and in vivo. Synthesis of a number of structural analogues indicated that the amino-terminal deca, undeca and dodecapeptides of prealbumin as well as some of their derivatives were also able to restore Az sensitivity to RFC in vitro and in vivo. The Cys10 residue and the Glu7 residues both contributed significantly to potency in vitro. Removal of up to three amino acids from the N-terminus of the decapeptide led to a progressive loss of activity. The data indicates that the ability of human prealbumin to restore the Az sensitivity to the RFC of adult Tx mice is intrinsic to the protein and resides in the amino-terminal domain of the molecule.

Amino Acid Sequence↗