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P Mason

Publications and source records attributed to P Mason.

At least 127 records · Page 7Linked to original sources
PubMed1991

Neurotransmitters in nociceptive modulatory circuits.

Significant advances have been made in our understanding of nociceptive modulation from RVM. Among the most useful conceptually has been the discovery that there are two classes of modulatory neurons in the RVM that are likely to have opposing actions on nociception: on-cells, which may facilitate nociceptive transmission, and off-cells, which probably have a net inhibitory effect on nociception. The similarity in response properties among the members of each class, their large, somatic "receptive fields," and the wide distribution of the terminal fields of axons of individual neurons to the trigeminal sensory complex and to multiple spinal segments indicate that these neurons exert a global influence over nociceptive responsiveness. Drug microinjections into the RVM presumably shift the balance between states of on- or off-cell firing and also produce measurable changes in the threshold for nocifensor reflexes. The meaningful unit of function in the RVM nociceptive modulatory system therefore probably consists of large ensembles of physiologically and pharmacologically similar neurons. The strong coordination of activity of the two classes of RVM neuron may depend largely upon intranuclear projections from RVM off-cells that excite other off-cells and inhibit on-cells. The off-cell pause is GABA-mediated, and it is likely that there is a subset of GABA-containing RVM on-cells that directly inhibit off-cells. Furthermore, the available evidence indicates that exogenous opiates activate off-cells by inhibiting GABAergic release. Presumably, enkephalinergic cells in the RVM disinhibit off-cells in a similar way. Although non-serotonin-containing off-cells certainly exist, we propose that some off-cells contain serotonin. Other possible connections are based on more limited data; however, ACh, neurotensin, NE, and EAAs are present in neurons that project to the RVM, and each of these compounds, when microinjected into the RVM, has a modulating effect on nociceptive transmission. The local circuits in the RVM that underlie these actions remain to be elucidated. At the level of the dorsal horn, there is good evidence for each of three inhibitory mechanisms: direct inhibition of nociceptive projection neurons, inhibition of excitatory relay interneurons, and excitation of an inhibitory interneuron. The relative contribution made by each of these circuits is unknown.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

In vitro use of Schwann cells to elucidate neurotoxic injury.

Schwann cells are responsible for the maintenance of the peripheral myelin sheath and neurotoxic insult directed against these cells can result in demyelination with a concomitant loss of neural function. We have utilized several in vitro techniques to investigate the effects of neurotoxins on the complex interactions between SC and axons. SC may be isolated from fresh neonatal sciatic nerves and used to examine the effect of neurotoxins on the axonal membrane induction of SC proliferation and specific myelin protein mRNA expression. We have recently devised a method to obtain SC from frozen sciatic nerves. This method allows pooling of neonatal nerves to generate enough cells for subsequent study. We have also transfected primary Schwann cells with a plasmid containing the large T antigen to obtain a SC line suitable for neurotoxicology studies. The functional status of cultured SC may also be studied via expression of SC specific antigens such as glial fibrillary acidic protein, CNPase, S100, laminin, P0 and myelin basic protein. We also propose culturing SC with dorsal root ganglion neurons to investigate the effect of neurotoxins on all stages of SC maturation, from proliferation to the in vitro synthesis of a compact myelin sheath. These strategies will allow us to investigate the cellular mechanisms of neurotoxicity in the PNS.

Animals↗
PubMed1990

Somatodendritic morphology of on- and off-cells in the rostral ventromedial medulla.

The rostral ventromedial medulla (RVM) contains two classes of physiologically defined neurons, on-cells and off-cells, that are implicated in nociceptive modulation. In a continuing effort to detail the neural circuitry that underlies the activity of these two distinct neuronal types, the somatodendritic morphology of on- and off-cells was studied in the cat, rat, and ferret. In lightly anesthetized animals, on-cells increased and off-cells decreased their discharge rate during a withdrawal reflex evoked by noxious stimuli. Following their physiological characterization by using intracellular recording, on- and off-cells were injected with either horseradish peroxidase or biocytin and their somatodendritic arborizations were examined. Labeled on- and off-cells included fusiform and stellate cells of all sizes as well as large multipolar neurons. Although the somatic shape of both on- and off-cells in RVM was heterogeneous, off-cells tended to be fusiform neurons whose long axis was oriented mediolaterally. The dendritic domains of both on- and off-cells extended bilaterally past the lateral edge of the trapezoid body or pyramid and ventrally to, and sometimes including, the trapezoid body or pyramid. In contrast to their extensive mediolateral spread, the dendritic domains of both cell types were limited to the ventral half of the reticular formation and were compressed along the rostrocaudal axis. The dendritic arbor of individual on- and off-cells extended well beyond the cytoarchitectonic boundaries of any single nuclear region, within the domain delineated as the RVM. The spatial domains of the dendritic arbors of on- and off-cells are further evidence that the on- and off-cells throughout the RVM constitute an integrated unit in the modulation of nociceptive transmission.

Animals↗
PubMed1990

Sickness in the system.

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Acquired Immunodeficiency Syndrome↗
PubMed1989

Axonal trajectories and terminations of on- and off-cells in the cat lower brainstem.

Two physiologically defined classes of pontomedullary raphe neurons were intracellularly labeled in order to determine the target nuclei of their axonal projections. In the lightly anesthetized cat, cells either increased (on-cells) or decreased (off-cells) their discharge rate during the paw withdrawal reflex evoked by noxious pinch or heat. On- and off-cells were injected with horseradish peroxidase and the initial course of labeled axons through the lower brainstem was reconstructed. On-cell projections to the pontomedullary raphe and medial reticular nuclei were sparse. On-cells projected densely to regions of the lateral reticular formation and the ventrolateral medulla at both rostral and caudal medullary levels. In general, on-cells had few collaterals and spare axonal swellings. In contrast to on-cells, most off-cells had axons that collateralized densely within the brainstem raphe and adjacent reticular formation. Such collaterals were either local, within the neuron's dendritic field, or distant, involving a projection of 1-8 mm. One off-cell had a dense terminal field within the sensory trigeminal complex, a projection that may subserve the inhibition of trigeminal sensory neurons produced by raphe magnus stimulation. Well-labeled off-cells had numerous collaterals and dense regions of axonal swellings. In summary, off-cells terminated densely in the raphe magnus and adjacent reticular formation whereas on-cells projected predominantly to the ventrolateral medulla, a region implicated in autonomic control. Local off-cell collaterals provide an anatomical substrate that would enable off-cells to coordinate the activity of on- and off-cells through synaptic contacts.

Action Potentials↗
PubMed1989

Inhouse excellence.

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Allied Health Personnel↗
PubMed1989

Inflammatory cytokines induce synthesis and secretion of gro protein and a neutrophil chemotactic factor but not beta 2-microglobulin in human synovial cells and fibroblasts.

Exposure of human synovial cells and fibroblasts in monolayer culture to interleukin 1 results in prominent secretion of proteins with Mr values of 6000 and 7000. By N-terminal sequence analysis, the Mr-6000 protein is identified as the protein encoded by a recently described gro mRNA. The Mr-7000 protein is identical to a neutrophil chemotactic factor released from monocytes. Stimulation of normal human fibroblasts with tumour necrosis factor alpha also results in expression and secretion of these two proteins. In addition to these cytokine-induced proteins, we have identified beta 2-microglobulin as an Mr-8000 protein constitutively secreted by synovial cells.

Amino Acid Sequence↗
PubMed1989

Staging of carcinoma of the uterine cervix: MRI-surgical correlation.

Forty-six patients with carcinoma of the uterine cervix were examined with spin-echo magnetic resonance imaging (MRI) using a superconducting magnet operating at a field strength of 0.5 T. All subjects later underwent lymphadenectomy and, when appropriate, radical hysterectomy. Surgical-pathologic correlation was carried out in order to assess the accuracy of the imaging modality in the staging of the disease. In the detection of nodal involvement, the accuracy of MR was 76%. The accuracy in determination of tumour size approached 100%. In the assessment of parametrial and vaginal involvement, the accuracy was 85% and 100% respectively.

Adenocarcinoma↗
PubMed1989

A novel deletion within the upstream regulatory region of episomal human papillomavirus type 16.

The pattern of human papillomavirus type 16 (HPV-16) integration was studied in 23 invasive carcinomas of the cervix using subgenomic probes. Seventeen tumours contained integrated HPV-16 and in 13 of these there was evidence of disruption within the E1-E2 open reading frames (ORFs). In all cases the upstream regulatory region (URR)-E6-E7 ORFs was maintained intact. Two independently derived tumours were infected with episomal wild-type HPV-16 and an episomal variant of HPV-16 containing a 325 bp deletion within the URR (positions 7598 to 17) and a point mutation at position 20 (A to C). This is the first report of a variant HPV-16 which is likely to be both defective and transmissible. Loss of E2 expression and deletion of a large portion of the URR may be two of the mechanisms leading to altered HPV-16 early gene expression in cervical tumours.

Adenocarcinoma↗
PubMed1989

Value of colposcopy in sexually transmitted diseases clinic based on first year's experience.

Two hundred and thirty two patients underwent cervical colposcopy within the first year of establishing a colposcopy service in the sexually transmitted diseases clinic at St Mary's Hospital, London. Their mean age was 27 years. Cervical intraepithelial neoplasia (CIN) was identified in 68 of 81 (84%) patients whose smears showed dyskaryosis and who underwent biopsy. CIN was also detected in 14 of 41 (34%) patients who underwent biopsy and whose repeat smears were reported as giving normal results. The value of assessing two consecutive smears was evident, however, because none of the 99 patients with CIN had two normal smear results consecutively. Patients requiring treatment underwent laser ablation, which was provided in the department of gynaecology. These results show that colposcopy plays a vital part in managing patients with abnormal smears and indicate that genitourinary physicians need to give priority to developing colposcopy services in their specialty.

Adolescent↗
PubMed1988

Serotonin immunocytochemistry of physiologically characterized raphe magnus neurons.

To determine if PAG stimulation activates serotonin containing neurons in RM, intracellular techniques were used to identify raphe magnus (RM) cells that are excited by antinociceptive periaqueductal gray (PAG) stimulation in the cat. RM neurons that received a monosynaptic EPSP from PAG shock were intracellularly labeled with ethidium bromide. Intracellularly stained RM cells were large, medium and small sized neurons. To determine if these cells contain serotonin, sections containing intracellularly labeled RM neurons were processed for serotonin immunocytochemistry. None of the RM cells (N = 32) which were intracellularly stained with ethidium bromide contained immunoreactive serotonin. These results are evidence that non-serotonergic RM cells are activated by antinociceptive PAG stimulation; these cells may be important in the relay of PAG induced antinociception.

Action Potentials↗
PubMed1987

Edinger-Westphal nucleus: cells that project to spinal cord contain corticotropin-releasing factor.

Combined retrograde transport and immunocytochemical methods were used to determine whether neurons in the Edinger-Westphal complex (EW) that project to the spinal cord also demonstrate corticotropin-releasing factor-like immunoreactivity (CRF-LI). Large injections of horseradish peroxidase (HRP) into cervical spinal cord retrogradely labeled cells throughout the extent of the EW complex. Most retrogradely labeled EW neurons also exhibited CRF-LI, evidence that EW is the origin of a direct CRF-containing pathway which links the rostral mesencephalon with spinal cord.

Animals↗