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Biomedical subjects

B E Jones

Publications and source records attributed to B E Jones.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

GABA-synthesizing neurons in the medulla: their relationship to serotonin-containing and spinally projecting neurons in the rat.

GABA-synthesizing neurons were identified in the medulla of the rat by peroxidase-antiperoxidase (PAP) immunohistochemistry for glutamic acid decarboxylase (GAD). Using diaminobenzidine (DAB) either alone or intensified with silver, a relatively large number of GAD-immunoreactive neurons were evident within the reticular formation, raphe nuclei and vestibular nuclei. In all these areas, profuse GAD-immunoreactive varicosities appeared to contact the soma and dendrites of both non-GABA and GABA neurons. These observations suggest that GABA neurons may act as interneurons or local projection neurons within the medulla and accordingly exert a potent inhibitory and/or disinhibitory control on bulbar projection neurons. Within the ventral reticular formation (pars alpha and ventralis of the gigantocellular reticular field) and raphe magnus, large numbers of prominent GAD-immunoreactive neurons resembled in size and morphology and overlapped in distribution the serotonin-immunoreactive neurons of the same regions. However, by sequential double immunostaining utilizing DAB as a chromogen for serotonin (5-HT) and benzidine dihydrochloride (BDHC) for GAD, it was found that GAD-containing neurons were distinct from 5-HT-containing neurons. Following injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the upper cervical spinal cord and combined processing for WGA-HRP (using tetramethylbenzidine [TMB] with cobalt) and immunohistochemistry (with DAB), a contingent of spinally projecting neurons were found to contain GAD. The GAD-immunoreactive reticulo- and raphe-spinal neurons were most frequent within the pars alpha and ventralis of the gigantocellular reticular fields and the raphe magnus, where they were approximately equal in number to the coexistent, but distinct 5-HT spinally projecting neurons. GABA neurons of the medulla may thus contribute directly to the bulbar inhibitory influence upon spinal sensory and motor systems.

Animals↗
PubMed1991

Paradoxical sleep and its chemical/structural substrates in the brain.

As originally named for the ostensibly contradictory appearance of rapid eye movements and low voltage fast cortical activity during behavioral sleep, paradoxical sleep or rapid eye movement sleep, represents a distinct third state, in addition to waking and slow wave sleep, in mammals and birds. It is an internally generated state of intense tonic and phasic central activation that is contemporaneous with the inhibition of sensory input and motor output. In early studies, it was established that the state of paradoxical sleep was generated within the brainstem, and particularly within the pons. Pharmacological studies indicated an important role for acetylcholine as a neurotransmitter in the generation of this state. Local injections of cholinergic agonists into the pontine tegmentum triggered a state of paradoxical sleep marked by phasic ponto-geniculo-occipital spikes in association with cortical activation and neck muscle atonia. Following the immunohistochemical identification of choline acetyl transferase-containing neurons and their localization to the dorsolateral ponto-mesencephalic tegmentum, neurotoxic lesions of this major cholinergic cell group could be performed to assess its importance in paradoxical sleep. Destruction of the majority of the cholinergic cells, which are concentrated within the laterodorsal tegmental and pedunculopontine tegmental nuclei but extend also into the locus coeruleus and parabrachial nuclei in the cat, resulted in a loss or diminishment of the state of paradoxical sleep, ponto-geniculo-occipital spiking and neck muscle atonia. These deficits were correlated with the loss of choline acetyltransferase-immunoreactive neurons in the region, so as to corroborate results of pharmacological studies and single unit recording studies indicating an active role of these cholinergic cells in the generation of paradoxical sleep and its components. These cells provide a cholinergic innervation to the entire brainstem reticular formation that may be critical in the generation of the state which involves recruitment of massive populations of reticular neurons. Major ascending projections into the thalamus, including the lateral geniculate, may provide the means by which phasic (including ponto-geniculo-occipital spikes) and tonic activation is communicated in part to the cerebral cortex. Descending projections through the caudal dorsolateral pontine tegmentum and into the medial medullary reticular formation may be involved in the initiation of sensorimotor inhibition. Although it appears that the pontomesencephalic cholinergic neurons play an important, active role in the generation of paradoxical sleep, this role may be conditional upon the simultaneous inactivity of noradrenaline and serotonin neurons, evidence for which derives from both pharmacological and recording studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1991

Photochemically induced thrombosis of the precentral cortex impairs operant variable-interval spatial delayed alternation performance by rats.

A variable-interval spatial delayed alternation memory task was used to quantify the behavioral effects of photochemically induced thrombic infarction of the precentral (frontal) cortex. Upon achieving criterion on the behavioral task, rats received thrombicischemic lesions, predominantly limited to the medial precentral cortex, induced by injection of the fluorescein dye Rose Bengal and illumination of the skull above the target area. Beginning six days after surgery, rats were retested on the memory task. Compared to Sham-operated controls (n = 5), rats with precentral cortex lesions (n = 5) demonstrated a retention interval-dependent accuracy deficit (impaired at the longest retention interval only) and slower reaction time (increased response latency). These effects were significant only during the first week of postoperative testing. Rats with lesions also demonstrated a greater probability of a choice response throughout the three postoperative test weeks. The results suggest that photochemical thrombosis in the precentral cortex produces functional, behavioral consequences in rats which can be reliably and objectively measured.

Analysis of Variance↗
PubMed1991

Noradrenergic locus coeruleus neurons: their distant connections and their relationship to neighboring (including cholinergic and GABAergic) neurons of the central gray and reticular formation.

Noradrenergic LC neurons appear to be relatively unique in the brain, being unsurpassed in the divergence and ubiquity of their projections through the central nervous system. In this regard, they share certain characteristics with peripheral noradrenaline neurons of the sympathetic nervous system. As such they would be assumed to play a very general role in modulating the activity of large populations of neurons in multiple, functionally diverse systems. Like other periventricular and reticular neurons, they have the potential to receive afferent information from multiple sources via long dendrites, upon which the majority of their inputs from brainstem and forebrain may arrive. They appear closely related to the cholinergic neurons of the laterodorsal tegmental nucleus, their neighbors that are located medial and rostral to them within the periventricular gray and that have similarly oriented and positioned long dendrites that would allow reception of similar afferent input as the LC neurons and also possibly interaction with the LC neurons. As evidenced by input to the noradrenergic cell bodies in the compact portion of the nucleus, a moderate GABAergic innervation, that may derive in part from local neurons, could have a potent influence on the activity of the cells. Periventricular GABAergic cells could also serve as intermediaries to other afferent input, from a distance, terminating in the periventricular region or from local neurons such as the cholinergic cells of the laterodorsal tegmental nucleus.

Acetylcholine↗
PubMed1991

The role of noradrenergic locus coeruleus neurons and neighboring cholinergic neurons of the pontomesencephalic tegmentum in sleep-wake states.

Despite early suppositions that the noradrenergic (NA) locus coeruleus (LC) neurons play a critical role in the generation and tonic maintenance of wakefulness and paradoxical sleep, further studies indicated that these cells play a nonessential modulatory role in the regulation of these states. Thus, based upon evidence from pharmacological, lesion and single-unit recording studies, it now appears that NA neurons may be important for enhanced periods of attention or stress during wakefulness, though they are not necessary for the tonic maintenance of cortical activation or behavioral arousal during the state. From similar examinations, it has been found that the cessation of activity of NA LC neurons may normally be important in permitting the occurrence of the state of paradoxical sleep. Neighboring cholinergic neurons of the pontomesencephalic tegmentum may also be active during waking and play a role in facilitating thalamocortical activity and transmission, like NA neurons during that state. However, unlike the NA neurons, the cholinergic neurons play an active and essential role in the generation of the state of paradoxical sleep. Generation of the state of paradoxical sleep may depend upon the simultaneous activation of cholinergic neurons and cessation of NA LC neurons, that could be brought about by the intermediary action of local GABA neurons.

Acetylcholine↗
PubMed1991

A comparative study of cultured vascular and lymphatic endothelium.

There is comparatively little knowledge of the structure and function of cultured lymphatic endothelium. A study was carried out to compare the intrinsic growth characteristics of cultured lymphatic endothelial cells with cultured endothelial derived from blood vessels. It was found that cultured lymphatic endothelium has growth requirements and growth characteristics similar to vascular endothelium. It also possesses FVIIIRA and Weibel-Palade bodies for specific identification. The results of this study have provided important base line data for subsequent studies of the pathobiology of lymphatic endothelium.

Animals↗
PubMed1990

NMDA receptor agonists derived from ibotenic acid. Preparation, neuroexcitation and neurotoxicity.

The two heterocyclic aspartic acid and glutamic acid analogues derived from ibotenic acid, (RS)-2-amino-2-(3-hydroxy-5-methylisoxazol-4-yl)acetic acid (AMAA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) have previously been shown to be selective agonists at N-methyl-D-aspartic acid (NMDA) and AMPA receptors, respectively. Two analogous series of AMAA and AMPA derivatives have now been synthesized and characterized in receptor binding studies and neuropharmacological experiments. AMAA was shown to be a very potent NMDA agonist in cortical tissue preparations, slightly more active than NMDA, whereas N-methyl-AMAA was less potent and N,N-dimethyl-AMAA almost inactive. (RS)-3-Hydroxy-4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-4-carboxylic acid (4-HPCA), a bicyclic analogue of AMAA, exhibited weak NMDA agonist effects similar to those of quinolinic acid. The relative potency as AMPA receptor agonists of AMPA, N-methyl-AMPA, N,N-dimethyl-AMPA and (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-5-carboxylic acid (5-HPCA), a bicyclic analogue of AMPA, was distinctly different from that of the AMAA series of compounds as NMDA agonists. The pharmacological and toxicological profiles of AMAA and 4-HPCA, compared with those of quinolinic acid, are consistent with heterogeneity of NMDA receptors.

Animals↗
PubMed1990

Immunohistochemical study of choline acetyltransferase-immunoreactive processes and cells innervating the pontomedullary reticular formation in the rat.

The present study was undertaken to examine the cholinergic innervation of the brainstem reticular formation in an effort to understand the potential role of cholinergic neurons in processes of sensory-motor modulation and state control. The cholinergic cells and processes within the pontomedullary reticular formation were studied in the rat by application of peroxidase-antiperoxidase immunohistochemistry with silver intensification for choline-acetyltransferase (ChAT). ChAT-immunoreactive cells were located in the pontomesencephalic tegmentum within the laterodorsal and pedunculopontine tegmental (LDT and PPT) nuclei, where they numbered approximately 3,000 on each side and were scattered in the midline, medial, and lateral medullary reticular formation, where they numbered approximately 10,000 in total on each side. The cholinergic neurons within the reticular formation were commonly medium in size and gave rise to multiple dendrites that extended for considerable distances within the periventricular gray or the reticular formation, as is typical of other isodendritic reticular neurons. A prominent innervation of the entire pontomedullary reticular formation was evident by varicose ChAT-immunoreactive fibers that often surrounded large noncholinergic reticular neurons in a typical perisomatic pattern of termination, suggesting a potent influence of the cholinergic innervation on pontomedullary reticular neurons. The contribution of the pontomesencephalic cholinergic neurons to the innervation of the medial medullary and lateral pontine reticular formation was studied by retrograde transport of horseradish peroxidase conjugated wheat germ agglutinin (WGA-HRP) in combination with ChAT immunohistochemistry. A proportion of the cholinergic neurons within the laterodorsal tegmental nucleus (pars alpha) and the pedunculopontine tegmental nucleus were retrogradely labelled on the ipsilateral (10-15%) and contralateral (5-10%) sides from the medial medullary reticular formation, indicating a significant contribution to the cholinergic innervation of this region, which, however, also appeared to derive in part from intrinsic medullary cholinergic neurons. The major fiber system by which the medial medullary reticular formation was reached by the pontomesencephalic cholinergic neurons appeared to correspond to the lateral tegmentoreticular tract. Fibers passed from these cholinergic cells ventrally through the lateral pontine tegmentum, in the region of the subcoeruleus, where they also appeared to innervate by fibres en passage the noncholinergic neurons of the region. A significant proportion of the pontomesencephalic cholinergic neurons were retrogradely labelled from the lateral pontine tegmentum.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗