Search PubMed⌕ Search

Biomedical subjects

P Mason

Publications and source records attributed to P Mason.

At least 91 records · Page 5Linked to original sources
PubMed1995

The density and distribution of serotonergic appositions onto identified neurons in the rat rostral ventromedial medulla.

Neurons in the rostral ventromedial medulla (RVM) contribute to the modulation of nociceptive transmission and to the analgesic effects of opioids. The RVM contains serotonergic terminal arbors, serotonergic neurons and several types of serotonin (5-HT) receptors. Limited evidence suggests that 5-HT acting within RVM decreases nociceptive responsiveness and contributes to opioid analgesia. The present study examines the density and distribution of serotonergic afferents onto physiologically identified neurons in the RVM. In anesthetized rats, RVM neurons were characterized by their response to noxious stimulation as either on (excited), off (inhibited) or neutral (unaffected) cells. Tissue containing intracellularly labeled RVM neurons was processed for 5-HT immunocytochemistry. Five off, five on, and three serotonergic neutral cells were examined with the confocal microscope for appositions between 5-HT immunoreactive (5-HT-IR) processes and intracellularly labeled processes. Serotonergic neutral cells had the highest density of 5-HT-IR appositions. The density of 5-HT-IR appositions onto off cells was slightly lower. On cells demonstrated the lowest density of 5-HT-IR appositions. These results indicate that 5-HT contributes to nociceptive modulation by direct actions on the activity of RVM cells. Because the RVM has several sources of serotonergic input and a number of different 5-HT receptor subtypes, further understanding of the role of RVM 5-HT afferents will require pharmacological studies to determine the action of 5-HT on each cell class and anatomical studies to determine the brainstem origin of serotonergic input to each cell class.

Analysis of Variance↗
PubMed1994

Promoter function of the human glucose-6-phosphate dehydrogenase gene depends on two GC boxes that are cell specifically controlled.

Human glucose-6-phosphate dehydrogenase is expressed in all cells by a housekeeping gene whose regulatory 5'-flanking sequence includes at least nine GC boxes. By transient transfection of HeLa and HepG2 cells with constructs containing glucose-6-phosphate dehydrogenase gene regions linked to a reporter gene, we have now delineated the core promoter and have located upstream stimulatory and inhibitory sequences. By mutational analysis, we demonstrate that the activity of the core promoter requires two out of seven GC boxes. We show that stimulatory protein 1 (Sp1)-related factors and activator protein 2 (AP-2)-related proteins bind to these two boxes in band-shift experiments. One point mutation that affects the binding of only the Sp1-related factors to one or both boxes causes a marked decrease of promoter activity in HepG2 cells but not in HeLa cells. We conclude that (a) two out of many seemingly redundant GC boxes are necessary to drive a G+C-rich housekeeping promoter; (b) factors that bind to GC boxes may exert cell-type-specific regulation of housekeeping gene promoter activity; (c) point mutations in the promoter of the glucose-6-phosphate dehydrogenase gene can inhibit its transcription.

Base Sequence↗
PubMed1994

Somatic mutations and cellular selection in paroxysmal nocturnal haemoglobinuria.

Patients with paroxysmal nocturnal haemoglobinuria (PNH) have in their blood two red-cell populations, one normal and one deficient in proteins anchored to the membrane through a glycan phosphatidylinositol (GPI) structure. The PNH abnormality is due to a somatic mutation in the PIG-A gene, whose product is required for an early step in GPI anchor biosynthesis. We show that in two patients, two PNH clones with different mutations co-exist, and must therefore have arisen independently. This finding supports the concept that PNH develops under the pressures of a positive selection mechanism whereby GPI-anchor-deficient haemopoietic cells have a survival advantage.

Cell Line↗
PubMed1994

Residence of incident cohort of psychotic patients after 13 years of follow up.

OBJECTIVE: To establish the residential history of an incident cohort of psychotic patients 13 years after their first contact with the psychiatric services. DESIGN: Tracing of all patients admitted to the WHO study on determinants of outcome of severe mental disorders in Nottingham between 1978 and 1980. Patients were assessed using standardised and comparable instruments, and extra information was obtained from key informants and medical records. SETTING: Catchment area of Nottingham psychiatric services. MAIN OUTCOME MEASURES: Main place of residence over the previous two years and residential history over 13 years in terms of homelessness, imprisonment, and use of high dependency psychiatric facilities. RESULTS: 95 patients were traced. At the point of follow up no patients were in long stay psychiatric wards, two were in supervised residence, none was homeless, and none was in prison or a high security hospital. 85 patients were living either independently alone or with their family or friends in the community. Of these, 44 had had no contact with the psychiatric services at the point of follow up. CONCLUSIONS: Although many patients experienced a difficult early course of illness, the longer term outcome of the disorder was associated with remarkably low periods of homelessness and imprisonment and low use of intensive care facilities. These findings offer some reassurance, given the concerns about the effectiveness of community oriented care for this potentially most vulnerable group of psychiatric patients.

Adult↗
PubMed1994

Sequence of the S fragment of foot-and-mouth disease virus type A12.

The foot-and-mouth disease virus (FMDV) genome contains a 5' untranslated region (S fragment) capable of forming a stem-loop structure of over 350 bases, which is separated from the remainder of the genome by a homopolymeric cytidylic acid tract (poly(C)) of variable length. The sequence of the S fragment of serotype A12 appears more similar to those of type O1 or type C3 than to subtype A10. The relatively large difference between the S fragment sequences of two type A viruses suggests that the sequences per se of this region of the genome are not critical for the maintenance of function, and suggests the possibility of a relatively recent recombination event within the poly(C) region of the A12 genome.

Amino Acid Sequence↗
PubMed1994

Methods for the determination of target skin distances when obstructions block visual measurement.

The target to skin distance (TSD) is one of the most common measurements taken for radiation therapy. This value is used for determination of the depth at which the treatment time is calculated. The optical distance indicator (ODI) is most often used to find the TSD. However, the ODI relies on a clear line of sight. The three methods presented can be used when the ODI is obstructed.

Humans↗
PubMed1994

Audit of the use of doctors' holding power under Section 5(2) of the Mental Health Act 1983.

The legal documentation and hospital case-notes of all patients detained during 1989 in Nottingham and Lincoln under Section 5(2) of the Mental Health Act 1983 (empowering the emergency detention of a voluntary inpatient who wishes to leave), were audited to establish if there were any predictors of conversion to longer-term restraint under that Act. Of the 146 Section 5(2) orders, 80 were converted to a Section 2 or 3; the conversion rate in people detained outside normal working hours and those detained within 12 hours of admission was significantly lower; and the conversion rate was significantly higher in people with a mental illness, compared with those with personality disorders, substance abuse and stress reactions. No differences existed in the overall conversion rates of people managed by senior or junior doctors, but junior doctors who did not seek the advice of a senior doctor had a significantly lower rate of conversion than those who did. These results indicate that Section 5(2) may have been inappropriately used in up to 45% of cases, and underline the need for appropriate consultation.

Commitment of Persons with Psychiatric Disorders↗
PubMed1994

Serotonin immunoreactivity is contained in one physiological cell class in the rat rostral ventromedial medulla.

Neurons in the rostral ventromedial medulla (RVM) are the major source of serotonergic projections to the dorsal horn. A large body of evidence implicates RVM serotonergic neurons in the modulation of spinal nociceptive transmission. Three physiological classes of RVM neurons, on, off, and neutral cells, are postulated to have different nociceptive modulatory effects on spinal nocifensor reflexes. This study was undertaken to determine which RVM cell class(es) contains 5-HT. In anesthetized rats, RVM neurons were identified by their responses to noxious cutaneous stimuli, intracellularly labeled, and processed for 5-HT immunocytochemistry. Labeled neurons were examined with epifluorescence and imaged using a confocal laser microscope. A total of 25 RVM neurons were intracellularly labeled. No off (n = 9) or on (n = 8) cells were serotonergic. Half of the neutral cells (4 of 8) demonstrated 5-HT immunoreactivity. These results call for a reevaluation of the mechanisms of RVM modulatory influence on spinal cord nociceptive transmission. The finding that some neutral cells are serotonergic strongly suggests that serotonergic neutral cells are involved in the modulation of spinal nociceptive transmission. Additionally, inhibition of spinal nociceptive transmission by off cells is unlikely to involve 5-HT release. Finally, since opioid administration does not alter the firing of RVM neutral cells, the results of the present study indicate that serotonergic RVM neurons do not directly mediate the effects of supraspinal opioids in the rat.

Animals↗
PubMed1994

Control of microwave heating of peritoneal dialysis solutions.

OBJECTIVE: To determine if microwave heating of dialysis solutions to 37 degrees C produced focal overheating (hot spots) and caramelization of dextrose. DESIGN: In vitro determination of conditions for controlling time, temperature, and procedures. Bags had been stored at ambient room temperature. MAIN OUTCOME MEASURES: Solution and external bag surface temperature determinations. Dextrose degradation products determined spectrophotometrically. Microscopy for potential caramel precipitates. RESULTS: A microwave oven with no rotation tray produced uneven heating of bags of two commercially available concentrations of dialysis solutions. The greatest hot spots were evident in spike ports. External bag surface temperatures were within 0.20 degrees C of reservoir temperatures. Initial solution temperatures correlated with temperatures of the solutions after microwave heating (r = 0.895). No statistically significant differences were found between dextrose degradation product concentrations of unheated and heated solutions, including hot spots. No precipitates were observed microscopically. CONCLUSIONS: Despite the presence of solution hot spots in bag infusion ports, 37 degrees C temperatures were achievable in the bag reservoirs with no evidence of increased glucose degradation. This outcome is assured if the initial temperature and the microwave conditions (procedure, time, mixing of solution) are held constant, and the external bag temperatures are measured after heating.

Dialysis Solutions↗
PubMed1993

Three-dimensional analysis of the dendritic domains of on- and off-cells in the rostral ventromedial medulla.

The rostral ventromedial medulla 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 three-dimensional somatodendritic morphology of on- and off-cells was studied in the cat and the rat. Following physiological characterization with intracellular recording, on- and off-cells were injected with horseradish peroxidase and sectioned in the coronal plane. Their somatodendritic arborizations were reconstructed with the aid of a computerized three-dimensional reconstruction program. There were no differences between on- and off-cells in any somatodendritic feature analyzed. On- and off-cells possess dendritic arbors that are elongated in the mediolateral axis relative to the dorsoventral and rostrocaudal axes. In the rat, the average dendritic extent was more than 1,400 microns mediolaterally but only about 800 microns in either the dorsoventral or rostrocaudal axis. All somatic and dendritic measures were greater for both cat cells than for any rat neuron. Dendrites and their tips were located predominantly in regions lateral to the soma. The center of total dendritic length was usually located within 150 microns of the soma, most frequently ventral and lateral to the soma. The present results demonstrate that the dendritic domains of neurons in the nuclei raphe magnus and reticularis paragigantocellularis pars alpha are not contained within cytoarchitechtonic boundaries. On- and off-cell dendrites are interdigitated throughout the mediolateral extent of the rostral ventromedial medulla. Since on- and off-cell dendritic domains occupy a restricted rostrocaudal plane, afferents to the rostral ventromedial medulla that are confined to a single coronal plane and those that collateralize at several levels are likely to play different roles in the control of on- and off-cell activity.

Animals↗
PubMed1993

Captive market.

Explore the source record for details and available documents.

Competitive Bidding↗
PubMed1993

Lipopolysaccharide induces fever and decreases tail flick latency in awake rats.

In humans, somatic aches and pains are frequently reported during fever. To determine whether exogenous pyrogen administration increases nociceptive responsiveness in rats, the tail flick reflex evoked by noxious heat was compared in animals that received an intraperitoneal injection of exogenous pyrogen (lipopolysaccharide) or vehicle (saline). There were no differences in skin temperature between lipopolysaccharide- and vehicle-injected rats. Awake rats injected with lipopolysaccharide exhibited an increase in colonic temperature and a decrease in tail flick latency when compared to vehicle-injected rats. Neural events that trigger fever may therefore also modulate nociceptive responsiveness.

Animals↗
PubMed1993

Soft cell.

A shake-up in the healthcare system at the western world's largest remand centre in New York City means sick prisoners are better off in jail, reports Peter Mason.

Contract Services↗
PubMed1993

Characterization of cathepsin B specificity by site-directed mutagenesis. Importance of Glu245 in the S2-P2 specificity for arginine and its role in transition state stabilization.

The pH dependence of cathepsin B-catalyzed hydrolyzes is very complex. At least seven dissociable groups are involved in the binding and hydrolysis of 7-amido-4-methyl coumarin and p-nitroaniline (pNA)-based substrates containing a P1 Arg and either a Phe or Arg at the P2 position. By site-directed mutagenesis we show that a previous suggestion, that Arg202 is one of the groups which influences the pH dependence of cathepsin B-catalyzed hydrolysis of the Z-Arg-Arg-pNA substrate, is not valid. However, it was found that Glu245, which has a pKa of 5.1 in rat cathepsin B, is responsible for the S2-P2 specificity for Arg-containing substrates and controls the pH dependence of their hydrolysis. Furthermore, the data indicate that Glu245, which forms a hydrogen bond with the guanidinium group of the substrate's P2 Arg, contributes about 1.8 kcal/mol to transition state stabilization in the protonated state and about 0.6 kcal/mol in the deprotonated state. Mutation of Glu245 to Gln results in a 16-fold decrease in kcat but does not affect Km. While cathepsin B has a 7-fold preference for Phe over Arg at the P2 position of a substrate, binding of the aromatic side chain does not appear to be influenced by Glu245.

Amino Acid Sequence↗
PubMed1993

Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody.

Fifty-two patients with epithelial ovarian cancer were treated with yttrium-90-labelled monoclonal antibody HMFG1 administered intraperitoneally following conventional surgery and chemotherapy as part of an extended phase I-II trial. The treatment was well tolerated and the only significant toxicity observed was reversible myelosuppression as previously described. Following conventional surgery and chemotherapy, 21 out of the 52 patients had no evidence of residual disease and were regarded as receiving treatment in an adjuvant setting. To date, two of these patients have died of their disease (follow-up 3-62 months, median follow-up 35 months). This extended phase I-II study suggests that patients with advanced ovarian cancer who achieve a complete remission following conventional therapy may benefit from further treatment with intraperitoneal radioactive monoclonal antibody.

Actuarial Analysis↗
PubMed1993

Anesthetic potency (MAC) is independent of forebrain structures in the rat.

BACKGROUND: The ability of general anesthetics to suppress somatomotor responses to surgical incision and other noxious stimuli is of particular clinical relevance. When the blockade is due to inhaled agents, this effect can be quantified as the minimum alveolar concentration (MAC), i.e., that concentration that blocks movement evoked by a noxious stimulus (ED50). METHODS: To identify the neural structures that subtend this somatomotor response, we anesthetized 14 rats with isoflurane in oxygen and performed bilateral parietal-temporal craniotomies. In each rat, MAC was repeatedly tested using tail-clamping and Dixon's up-down concentration technique. After determination of baseline MAC, seven rats underwent aspiration decerebration, after which MAC was repeatedly measured. RESULTS: In the control group (N = 7), MAC (mean +/- SD) remained constant at 1.30 +/- 0.25% for more than 6 h. In the seven rats that underwent aspiration decerebration, baseline MAC was 1.26 +/- 0.14%. These seven rats with histologically validated precollicular decerebration demonstrated no change in MAC relative to control rats, as much as 11 h after decerebration (P = 0.14). CONCLUSIONS: These findings suggest that the anesthetic-induced unresponsiveness to noxious stimuli measured by MAC testing does not depend on cortical or forebrain structures in the rat.

Administration, Inhalation↗
PubMed1993

Genetic transformation and phylogeny of bacterial symbionts from tsetse.

Two isolates of bacterial endosymbionts, GP01 and GM02, were established in cell free medium from haemolymph of the tsetse, Glossina pallidipes and G. morsitans. These microorganisms appear similar to rickettsia-like organisms reported previously from various tsetse species. The 16S rRNA sequence analysis, however, placed them within the gamma subdivision of the Proteobacteria, phylogenetically distinct from most members of the Rickettsiaceae which align with the alpha subdivision. Distinct multiple endogenous plasmids are harboured by GP01 and GM02, suggesting that the two isolates are different. Restriction mapping analysis showed that one of the conserved plasmids is present in high copy number and is at least 80 kb in size. A heterologous plasmid pSUP204, which contains the broad host range oriV replication origin, was used to transfect bacterial cultures. The symbiont GM02 was transformed, and it expressed plasmid encoded resistance to the antibiotics ampicillin, tetracycline and chloramphenicol. Transformation of these symbionts may provide a novel means for expressing anti-parasitic genes within tsetse populations.

Animals↗