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B E Jones

Publications and source records attributed to B E Jones.

At least 19 recordsLinked to original sources

Interactions between HIV-infected monocytes and the extracellular matrix: HIV-infected monocytes secrete neutral metalloproteases that degrade basement membrane protein matrices.

The frequency of human immunodeficiency virus (HIV)-infected monocytes that spread on a model basement membrane was about twofold greater than that of an equal number of uninfected control cells through the initial 12 to 18 h of culture. By 24 h, virtually all HIV-infected and uninfected control cells spread on the basement membrane gel. The frequency of spread cells in the uninfected control population was less than 10% of total cells by 12 days. In contrast, 30 to 40% of HIV-infected monocytes remained spread through this time interval and formed a dense interdigitated network of cell processes on and into the gel matrix. Invasion of the basement membrane matrix by HIV-infected monocytes suggested increased secretion of proteases able to digest the gel. Indeed, levels of neutral protease activity in culture fluids from HIV-infected monocytes were significantly higher than those from equal numbers of uninfected control cells. High levels of protease activity in culture fluids of HIV-infected monocytes required productive virus infection and were not observed with cells exposed to T cell-tropic HIV isolates. The predominant protease activity in these cultures was a 92-kd neutral metallogelatinase. HIV-induced changes in monocyte metalloprotease activity may be important for extravasation of infected cells to tissue or for the development of AIDS-associated neuropathology, carcinogenesis, and opportunistic infection.

Basement Membrane

Cholinergic nucleus basalis neurons display the capacity for rhythmic bursting activity mediated by low-threshold calcium spikes.

Acetylcholine has long been known to play an important role in the cortical activation that accompanies the states of wakefulness and paradoxical sleep (for review, see Refs 17, 21) when this neurotransmitter is released from the cerebral cortex at the highest rates. The major supply of acetylcholine to the cerebral cortex arises from the cholinergic neurons of Meynert's Basal-ganglion or nucleus basalis of the forebrain. Lying in the substantia innominata within the major ascending pathway from the brain stem reticular formation, magnocellular basalis neurons project upon the cerebral cortex as the important ventral, extrathalamic relay of the ascending reticular activating system. Although the cholinergic basalis nucleus neurons have been shown to be important for cortical activation, the precise manner in which they influence cortical activity has not as yet been elucidated, in part because the cholinergic cells of this nucleus have not been identified in electrophysiological studies. Using intracellular recording in guinea-pig brain slices, we were able to record and fill with biocytin nucleus basalis neurons which were subsequently revealed by immunohistochemical staining to be choline acetyltransferase-positive and thus cholinergic. The cholinergic cells displayed rhythmic bursting activity mediated by a low-threshold calcium spike in vitro, which would endow them with a capacity for phasic (in addition to tonic) firing in vivo. By virtue of these different modes, cholinergic basalis neurons may accordingly deter or facilitate the cortical response to sensory input and may furthermore modulate the major frequencies of cortical activity across the different states of the sleep-waking cycle.

Animals

High resolution SPECT, small deep infarcts and diaschisis.

Eighteen cases of lacunar infarction are presented. Six of these cases had a purely motor clinical deficit. All the cases were studied by serial high resolution SPECT (single photon emission computerized tomography) using 99Tcm HMPAO. The degree and extent of the changes in cerebral perfusion consistent with diaschisis were noted and these compared with the severity of the clinical deficit at presentation and over time. No significant correlation between diaschisis and the clinical state was found at any stage. The nature, aetiology and importance of diaschisis are discussed and it is suggested that caution should be exercised in attributing clinical features to diaschisis simply because it may be present.

Aged

The anatomy of radioisotope lung scanning.

An appreciation of the appearances of segmental and lobar defects on a lung scan is important for the diagnosis of pulmonary embolism. The appearances of segmental and lobar ventilation defects of known anatomical location have been examined on 81mKr ventilation scans in normal human subjects, utilizing fibreoptic bronchoscopy to place temporary occlusions under direct vision at the orifices of lobar and segmental bronchi. Scans were obtained in the posterior, posterior-oblique and lateral projections. Anterior views were included if the defects could not be adequately visualized on the other views. The completeness of the occlusion and the site and size of each defect could be confirmed by ventilating the segment itself with 81mKr via the balloon catheter while the occlusion was maintained. Segmental defects located anterior to the hilum of the lung tended to be optimally visualized on the lateral view and defects located posterior to the hilum tended to be optimally visualized on the posterior-oblique view. The size of segmental defects could be underestimated on the lung scan, especially those involving the anterior and lateral basal segments of both lower lobes. Defects involving the medial basal segment of the right lower lobe were undetectable on any view. By implication, the same conclusions apply to 99mTc perfusion scans.

Adult

The effects of psychomotor stimulants on single-spatial alternation behavior in dogs.

Dogs were trained to pedal press for drinking water in a noncued, single-spatial alternation task. After the dogs were exhibiting stable performance at or above predetermined criteria levels, they were given three doses of four different drugs (methylphenidate, 0.2, 0.4, and 0.8 mg/kg; d-amphetamine, 0.15, 0.3 and 0.6 mg/kg; cocaine, 0.5, 1, and 2 mg/kg; and phenmetrazine, 0.6, 1.2 and 2.4 mg/kg). In general, all four drugs produced similar changes in performance. The number of correct responses was an especially sensitive indicator of drug effects. All four drugs also produced significant increases in both the average response latency and total session duration, but there were few significant changes in either the total number of responses or number of intertrial interval responses. Relative to d-amphetamine, the potencies of cocaine and phenmetrazine, but not methylphenidate, were generally higher for the measures of single-spatial alternation than for self-administration.

Animals

Elimination of paradoxical sleep by lesions of the pontine gigantocellular tegmental field in the cat.

Bilateral lesions of the pontine gigantocellular tegmental field in the cat resulted in the complete elimination of paradoxical sleep during 3 weeks postoperative recording. The tonic muscular atonia, normally characteristic of this state, was absent. The phasic components, rapid eye movements and ponto-geniculooccipital (PGO) spikes, did not occur in association with an activated EEG, as they normally do in paradoxical sleep. In fact, PGO spikes were virtually absent immediately after the lesion and were only secondarily apparent as isolated phenomena during slow wave sleep to represent in total daily number 5% of normal the first week and 15% of normal the third week after the lesion. These results indicate that neurons whose perikarya and/or processes are located within the pontine gigantocellular tegmental field and which are not part of the noradrenaline locus coeruleus complex, are critical for paradoxical sleep.

Animals

Serotonin neurons of the midbrain raphe: ascending projections.

The ascending projections of serotonin neurons of the midbrain raphe were analyzed in the rat using the autoradiographic tracing method. Axons of raphe serotonin neurons ascend in the ventral tegmental area and enter the medial forebrain bundle. A number of fibers leave the major group to ascend along the fasciculus retroflexus. Some fibers enter the habenula but the majority turn rostrally in the internal medullary lamina of the thalamus to innervate dorsal thalamus. Two additional large projections leave the medial forebrain bundle in the hypothalamus; the ansa peduncularis-ventral amygdaloid bundle system turns laterally through the internal capsule into the striatal complex, amygdala and the external capsule to reach lateral and posterior cortex, and another system of fibers turns medially to innervate medial hypothalamus and median eminence and form a contrelateral projection via the supraoptic commissures. Rostrally the major group in the medial forebrain bundle divides into several components: fibers entering the stria medullaris to terminate in thalamus; fibers entering the stria terminalis to terminate in the amygdala; fibers traversing the fornix to the hippocampus; fibers running through septum to enter the cingulum and terminate in dorsal and medial cortex and in hippocampus; fibers entering the external capsule to innervate rostral and lateral cortex; and fibers continuing forward in the medial olfactory stria to terminate in the anterior olfactory nucleus and olfactory bulb.

5,6-Dihydroxytryptamine

Effects of methadone and morphine maintenance on drug-seeking behavior in the dog.

The effects of methadone and morphine maintenance on morphine self-administration were studied in the dog. Methadone was given passively for 2 weeks by continuous i.v. infusion. The amount of methadone administered daily was the same in mg/kg as the mean daily mg/kg of morphine the dogs had self-administered during the premaintenance control week. Morphine self-administration was markedly reduced initially but returned to normal levels within 2 weeks of methadone administration. Following the methadone maintenance period, morphine self-administration was increased over the premaintenance period for 2 weeks. A result similar to that with methadone was obtained in a second experiment when morphine was used as the maintenance drug in an amount that was three times the amount the dogs had been self-administering during the premaintenance control week.

Animals

Ascending projections of the locus coeruleus in the rat. I. Axonal transport in central noradrenaline neurons.

Axonal transport of protein and metabolites of L-[3H(G)]3, 4-dihydroxyphenylalanine ([3H]DOPA) was studied in the central noradrenaline neurons of the pontine nucleus locus coeruleus and was correlated with regional alterations of noradrenaline content following destruction of the nucleus. Unilateral lesions of the locus coeruleus produce a partial depletion of noradrenaline in the ipsilateral hypothalamus and telencephalon, indicating that these neurons project widely to the ipsilateral forebrain. Twenty-four to 48 h following local injections of 50 micronCi [3H]proline, locus coeruleus neurons take up labeled material and transport it, presumably as protein, to ipsilateral structures in the midbrain, diencephalon and telencephalon including the neocortex. Similarly 8 h after injection of 25 micronCi [3H]DOPA into the locus coeruleus, transport of material including catecholamines occurs to ipsilateral diencephalon and telencephalon. Axonal transport of proteins to telencephalic structures is greatly diminished by selective lesions of catecholamine terminals with 6-hydroxydopamine (6-OHDA) and following destruction of the medial forebrain bundle. These results provide further support for the view that noradrenaline neurons of the locus coeruleus nucleus project widely within the neuraxis to ipsilateral structures of the brain stem, diencephalon and telencephalon, including all cortical areas. In addition, evidence is presented for a contralateral projection with a similar distribution. The rate of axonal transport of labeled protein and metabolites of [3H]DOPA including [3H]catecholamines in central noradrenaline neurons is estimated to be 3-4 mm/h and is accordingly similar to that reported for noradrenaline neurons of the peripheral sympathetic nervous system.

Adrenergic Fibers

Ascending projections of the locus coeruleus in the rat. II. Autoradiographic study.

The ascending projections of the locus coeruleus were studied using an autoradiographic method. The major projection of locus coeruleus neurons ascends in a dorsal pathway traversing the midbrain tegmentum in a position ventrolateral to the periaqueductal gray. At the caudal diencephalon the locus coeruleus axons descend to enter the medial forebrain bundle at a caudal tuberal hypothalamic level. They are jointed in the medial forebrain bundle by a much smaller locus coeruleus projection which takes a ventral course through the midbrain tegmentum and enters the medial forebrain bundle via the mammillary peduncle and ventral tegmental area. Terminal projections are evident in the midbrain to the periaqueductal gray, tegmentum and raphe nuclei. There are widespread projections to the dorsal thalamus. The heaviest of these are to the intralaminar nuclei, the anteroventral and anteromedial nuclei, the dorsal lateral geniculate and the paraventricular nucleus. In the hypothalamus the largest projections are to the lateral hypothalamic area, periventricular nucleus, supraoptic nucleus and paraventricular nucleus. As the locus coeruleus projection ascends in the medial forebrain bundle, fibers leave it to traverse the lateral hypothalamus and zona incerta and enter the internal capsule, the ventral amygdaloid bundle and ansa peduncularis. These appear to terminate in the amygdaloid complex and, via the external capsule, in the lateral and dorsal neocortex. At the level of the septum 4 projections are evident. One group of fibers enters the stria medullaris to terminate in the paraventricular nucleus and habenular nuclei. A second group joins the stria terminalis to terminate in the anygdaloid complex. The third group turns into the diagonal band and medial septum; some fibers terminate in the septal nuclei and others continue into the fornix to termimate in hippocampus. A large component continues around the corpus callosum into the cingulum to terminate in the cingulate and adjacent neocortex, the subiculum and hippocampus. The remaining fibers continue rostrally in the medial forebrain bundle to terminate in olfactory forebrain and frontal neocortex. Commissural projections arise at 4 locations. The first decussation occurs in the dorsal tegmentum just below the central gray rostral to the locus coeruleus. The crossing fibers enter the contralateral dorsal bundle. A second group of fibers leaves the ipsilateral dorsal pathway, crosses in the posterior commissure and enters the contralateral dorsal pathway at the level. The third commissural projection arises more rostrally and crosses in the dorsal supraoptic commissure to enter the contralateral medial forebrain bundle. The fourth commissural projection is through the anterior commissure. The termination of the contralateral projection appears similar to that of the ipsilateral projection.

Afferent Pathways

Effects of locus coeruleus lesions upon cerebral monoamine content, sleep-wakefulness states and the response to amphetamine in the cat.

The purpose of the present study was to investigate the effects of complete lesions of the noradrenaline locus coeruleus neurons upon wakefulness and paradoxical sleep. Radiofrequency lesions of the nucleus were performed in 8 chronically implanted cats which were continuously recorded with an EEG for 5 days prior to and 21 days following the lesions, when they were sacrificed. In 3 of these animals amphetamine (2 mg/kg) was administered on one control day and on the 10th day post-lesion. Following sacrifice, monoamine content was assayed in discrete brain regions, and the lesion was examined in Nissl-stained sections of the pons. (1) The majority (x 69%) of the locus coeruleus was bilaterally destroyed by the lesions which only minimally exceeded the boundaries of the nucleus within the dorsolateral pontine tegmentum. Noradrenaline was depleted by a mean of 85% in the paleo- and neocortex and by a mean of 60% in the thalamus and midbrain. (2) EEG activation reappeared within 12-48 h following the lesion and represented a normal percentage of recording time on the 3rd and subsequent days post-lesion. The behavioral arousal and long-lasting EEG activation produced by amphetamine was qualitatively and quantitatively the same pre- and post-lesion. (3) Despite alteration of certain components, paradoxical sleep reappeared within 48 h and recovered to normal amounts by the second week post-lesion. Muscle atonia was permanently absent in 7 animals. Ponto-geniculo-occipital (PGO) spiking was acutely redistributed across all states and chronically reduced in frequency (by a mean of 50%) within paradoxical sleep. These results indicate that the noradrenaline locus coeruleus neurons are not necessary for the tonic maintenance of EEG activation that occurs in normal wakefulness and in amphetamine-produced arousal. Furthermore, these neurons are not necessary for the occurrence of paradoxical sleep, although they may be involved in modulation of PGO spiking.

Animals

Characteristics of beta-phenethylamine self-administration by dog.

Phenethylamine (PEA), a biologically active amine found in the brain, maintained intravenous self-administration behavior by dogs previously trained to respond for amphetamine. Systematic changes in the unit dose of PEA (1.5 to 6.0 mg/kg/infusion) were negatively related to the number of infusions (91.3 to 29.5, respectively) per 4hr session. The mean intake of PEA was 165 mg/kg/session. Pretreatment with chlorpromazine (0.5 to 2.0 mg/kg, IV, 30 min prior to the session) produced a dose-dependent increase in the number of self-administered PEA infusions. However, there were no changes in responding for PEA following pretreatment with either the dopaminergic antagonist pimozide (5 to 40 micrograms/kg, IV, 30 min prior to the session) or the adrenergic antagonist phenoxybenzamine (1 to 8 mg/kg, IV, 30 min prior to the session). These data suggest that the reinforcing properties of PEA are not dependent on either a dopaminergic or adrenergic system.

Animals

Drug-seeking behavior in the dog: lack of effect of prior passive dependence on morphine.

Twelve dogs were made dependent on morphine (20 mg/kg per 24 hours) by intravenous passive administration of the drug. Six were gradually withdrawn and six were withdrawn abruptly. Subsequent tests for self-administration of morphine began within 8 to 18 weeks after morphine was last administered passively. Morphine was available for self-administration at several unit dose levels for 8 weeks. In comparison with control dogs administered with saline, there was no evidence that prior dependence on morphine influences subsequent self-administration of morphine, or that morphine is a primary reinforcer for dogs. Possible implications of these and related observations are discussed.

Animals

Axonal transport in serotonin neurons of the midbrain raphe.

The projections of serotonin-containing neurons of the midbrain raphe nuclei (nucleus raphe dorsalis, nucleus centralis superior) are studied by analysis of axonal transport of labeled amino acids. These results are correlated with regional alterations of serotonin content following midbrain raphe lesions which produce significant serotonin depletion in nearly all regions of the central nervous system. Twenty-four hours following injection of 100 muCi [3H]proline, raphe neurons have taken up labeled material and transported it, presumably as protein, to telencephalon, diencephalon, brain stem, the cerebellum and the spinal cord. This transport appears to take place predominantly in serotonin neurons. After injection of 100 muCi [3H]5-HTP into nucleus raphe dorsalis or nucleus centralis superior, the pattern of regional distribution of transported material is very similar to that obtained with tritiated proline. Selective lesions of serotonin terminals with 5.6-DHT result in greatly diminished axonal transport of proteins to all telencephalic, diencephalic and mesencephalic areas as well as to cerebellum, pons-medulla and spinal cord. Unilateral destruction of the medial forebrain bundle results in significant reduction in axonal transport of labeled material to ipsilateral telencehalon and thalamus. These results provide further support for the view that serotonin neurons of the midbrain raphe nuclei project widely throughout the neuraxis to telencephalon, diencephalon, brain stem, cerebellum and spinal cord.

Animals