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Biomedical subjects

R Mason

Publications and source records attributed to R Mason.

At least 55 records · Page 3Linked to original sources

Selective potentiation by ouabain of naloxone-induced withdrawal contractions of isolated guinea-pig ileum following acute exposure to morphine.

1. Ouabain, an inhibitor of Na+/K+ ATPase induces the release of acetylcholine from central and myenteric cholinergic neurones principally due to partial depolarization of the cell membrane. The effect of ouabain has been examined on neurogenic contractions in the guinea-pig ileum arising from either electrical field stimulation or from naloxone in morphine-exposed preparations. 2. Guinea-pig isolated ileum preparations were stimulated transmurally (0.1 Hz, 0.3 ms, 200 mA) to elicit contractions of the myenteric plexus-longitudinal smooth muscle. 3. Incubation with morphine (0.3 microM, 60 min) was followed by naloxone (1 microM) which produced withdrawal contractions in 16/26 preparations (median of 10.7 [2.2-40.0]% of a maximal contracture to KCl (60 mM)). 4. In parallel experiments, ouabain (1 microM) was added to the tissue before exposure to morphine (0.3 microM, 60 min). Naloxone (1 microM) subsequently displayed a withdrawal contraction in all 26/26 tissues (57.9 [30.5-151.7]% of a maximal contracture to KCl (60 mM). 5. Ouabain neither affected the concentration-dependent contractions of guinea-pig ileum produced by carbachol nor the inhibition of electrically-evoked contraction produced by morphine (0.3 microM). 6. The muscarinic antagonist atropine (0.1 microM) antagonized control naloxone withdrawal responses. The atropine resistant component, evident in ouabain-treated tissues, was blocked by SR140333((S)1-[2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenyla cetyl)piperidin-3-yl]ethyl]-4-phenyl-1-azoniabicyclo[2.2. 2]-octane, chloride), a substance P antagonist. 7. Clonidine (alpha2-adrenoceptor agonist) inhibited electrically-evoked contractions. Exposure to the alpha2-adrenoceptor antagonist RX811059 (2-(2-ethoxy-1,4-benzodioxan-2-yl)-2-imidazoline), resulted in a contracture which was not significantly enhanced by ouabain (1 microM). 8. Ouabain selectively potentiates the naloxone-induced withdrawal contraction following acute exposure to morphine the major components of which are mediated by both acetylcholine and substance P.

Adrenergic alpha-Agonists↗

Physical map of human 6p21.2-6p21.3: region flanking the centromeric end of the major histocompatibility complex.

We have physically mapped and cloned a 2.5-Mb chromosomal segment flanking the centromeric end of the major histocompatibility complex (MHC). We characterized in detail 27 YACs, 144 cosmids, 51 PACs, and 5 BACs, which will facilitate the complete genomic sequencing of this region of chromosome 6. The contig contains the genes encoding CSBP, p21, HSU09564 serine kinase, ZNF76, TCP-11, RPS10, HMGI(Y), BAK, and the human homolog of Tctex-7 (HSET). The GLO1 gene was mapped further centromeric in the 6p21.2-6p21.1 region toward TCTE-1. The gene order of the GLO1-HMGI(Y) segment in respect to the centromere is similar to the gene order in the mouse t-chromosome distal inversion, indicating that there is conservation in gene content but not gene order between humans and mice in this region. The close linkage of the BAK and CSBP genes to the MHC is of interest because of their possible involvement in autoimmune disease.

Bacterial Proteins↗

A paracrine role for myoepithelial cell-derived FGF2 in the normal human breast.

We have studied separated normal human breast epithelial and myoepithelial cells for the presence of basic fibroblast growth factor (FGF2) and its receptors, both low (heparan sulfate proteoglycans) and high affinity (FGFR1), and for the effects of FGF2 on the proliferation of both cell types. Our results indicate that these cells differ markedly in their synthesis and response to FGF2. We found, using PCR of purified cell populations, mRNA for FGF2 only in the myoepithelial cells, whereas immunostaining and Western blotting results demonstrated the presence of FGF2 protein in both epithelial and myoepithelial cells. FGF2 had no effect on the proliferation of myoepithelial cells, but it did maintain the survival of the separated epithelial cells in low serum and stimulate their growth in 5% and 10% FCS. Immunostainable FGFR1 was present in epithelial cells and, to a lesser extent, in myoepithelial cells. Low-affinity binding sites for FGF2 were synthesized by epithelial and myoepithelial cells, but myoepithelial cells possessed a greater proportion of higher-affinity heparan sulfate proteoglycans. These results indicate that myoepithelial cell-derived FGF2 may be an important paracrine factor controlling epithelial cell survival and growth in the normal human breast.

Blotting, Southern↗

Mechanical effect of the Angelchik prosthesis on the competency of the gastric cardia: pathophysiologic implications and surgical perspectives.

The Angelchik prosthesis appears to be effective in preventing gastroesophageal reflux, although its precise mechanism of action remains controversial. In a unique in vitro model, 10 freshly harvested canine esophagogastric specimens were tested for their ability to remain competent against challenges of intragastric pressure under controlled conditions of intra-abdominal pressure, longitudinal esophageal tension, lower esophageal sphincter pressure and overall length and circumference of the cardia (measure of gastric dilatation). Competency of the specimen was assessed by stepwise variation in the overall length of the sphincter, while keeping constant intraabdominal pressure (20 cm H2O), intragastric pressure (20 cm H2O), esophageal tension (physiologic), lower esophageal sphincter pressure (15 cm H2O) and degree of gastric dilatation (3 cm). With each specimen serving as its own control, the effect produced by the application of an Angelchik prosthesis was evaluated. Results consistently demonstrated that at any lower esophageal sphincter length the percent of competency was increased when the prosthesis was applied (P < 0.01). The findings indicate that the Angelchik prosthesis controls reflux by preventing unfolding of the lower esophageal sphincter when challenged by intragastric pressure.

Animals↗

Gallstone recurrence after successful dissolution therapy.

After successful dissolution therapy of cholesterol gallbladder stones bile again becomes supersaturated and recurrent gallstones may develop. Three different postdissolution treatments [500 mg ursodeoxycholic acid (UDCA) per day (N = 14, group I), 100 mg aspirin per day (N = 14, group II) and diet (N = 15, group III) versus a control group (no treatment, N = 15, group IV) aimed at preventing recurrence of gallstones were investigated in a prospective, randomized study in 58 gallstone patients (33 female, 25 male) after complete stone clearance. Bile samples (prior to dissolution therapy and at stone recurrence) were investigated for biliary cholesterol (C), phospholipids (PL), total bile acid concentration (BA), cholesterol saturation index (CSI), total lipid concentration (TLC), total biliary protein concentration (TP), and nucleation time (NT). In group IV multiple gallstones tended to recur more often than solitary stones (66.7% vs 16.7%) whereas in groups I-III only solitary stones recurred. Recurrent gallbladder stones were detectable in 10 patients (eight patients in group IV and one each in groups I and II, respectively) within one year after dissolution and in two patients (one each in groups III and IV, respectively) after 15 months. Furthermore, the probability of stone recurrence was significantly higher in untreated patients as compared to treated patients. In nine (group IV) of 12 patients with recurrent stones NT, C, CSI, PL, BA, TLC, TP, and bile acid spectrum remained nearly unchanged as compared to their pretreatment values, whereas in three (groups I-III) of 12 cases a decrease in C, CSI, and TP was observed during therapy. However, in each of these three patients, initial and after-treatment TP was significantly higher and NT shorter as compared to groups I-IV. Furthermore, in these cases (N = 3) NT was prolonged, whereas no significant changes were found in PL, BA, TLC, and bile acid spectrum. Recurrence of gallstones, which seems to occur more likely in patients with multiple stones as compared to solitary stones, will happen in the early stage after stone clearance, again causing biliary pain. UDCA, aspirin or diet will reduce the probability for recurrent stones after complete gallstone dissolution.

Adult↗

Orbitofrontal cortex neurons: role in olfactory and visual association learning.

1. The orbitofrontal cortex is implicated in the rapid learning of new associations between visual stimuli and primary reinforcers such as taste. It is also the site of convergence of information from olfactory, gustatory, and visual modalities. To investigate the neuronal mechanisms underlying the formation of odor-taste associations, we made recordings from olfactory neurons in the orbitofrontal cortex during the performance of an olfactory discrimination task and its reversal in macaques. 2. It was found that 68% of odor-responsive neurons modified their responses after the changes in the taste reward associations of the odorants. Full reversal of the neuronal responses was seen in 25% of these neurons. Extinction of the differential neuronal responses after task reversal was seen in 43% of these neurons. 3. For comparison, visually responsive orbitofrontal neurons were tested during reversal of a visual discrimination task. Seventy-one percent of these visual cells showed rapid full reversal of the visual stimulus to which they responded, when the association of the visual with taste was reversed in the reversal task. 4. These demonstrate that of many orbitofrontal cortex olfactory neurons on the taste with which the odor is associated. 5. This modification is likely to be important for setting the motivational value of olfactory for feeding and other rewarded behavior. However, it is less complete, and much slower, than the modifications found or orbit frontal visual during visual-taste reversal. This relative inflexibility of olfactory responses is consistent with the need for some stability is odor-taste associations to facilitate the formation and perception of flavors.

Acoustic Stimulation↗

The challenge of genuine power sharing in participatory research: the gap between theory and practice.

Participatory research is often suggested as a strategy to overcome power imbalances between researchers and research "subjects" because it values equally the knowledge of each individual who participates in the project. However, there is little documentation of the dilemmas that may arise when a complex community service organization attempts to engage in participatory research. In our experience of a participatory research project with multiple partners, power imbalances arose from organizationally based perspectives that were unaccounted for in the participatory research literature, demonstrating that power is a complex and elusive factor in establishing equal relations.

Clinical Trials as Topic↗

Iso- or antiperistaltic anastomosis: does it matter?

To assess the importance of gastrojejunal anastomoses being performed in an isoperistaltic manner, 25 rats underwent solid and liquid gastric emptying studies before and at 1, 2, 3, 4, 8, 12 and 16 weeks after a Polya-type gastrectomy. No differences between the two anastomotic directions were evident, either in the deaths associated with post-operative gastric dilatation, or in the rates of solid and liquid gastric emptying following surgery.

Animals↗

Palliation of malignant dysphagia: an alternative to surgery.

This paper presents the results of palliative treatment of 474 patients with malignant dysphagia. Laser produces good relief of symptoms but requires frequent repetition. Self-expanding metal stents provide one-off relief of dysphagia but do have complications. A randomised trial of laser versus covered and uncovered metal stents has demonstrated improved relief of dysphagia of stents over laser, but highlighted the problems at the cardia when stents are used. Chemotherapy in patients with advanced adenocarcinoma using epirubicin, cisplatin and 5-fluorouracil produces a response in two-thirds of cases, with relief of dysphagia and possible increase in survival. A treatment plan for palliation of patients with malignant dysphagia is presented.

Adult↗

Agmatine recognizes alpha 2-adrenoceptor binding sites but neither activates nor inhibits alpha 2-adrenoceptors.

It has been suggested that agmatine (decarboxylated arginine) is an endogenous clonidine-displacing substance (CDS) which recognizes alpha 2-adrenoceptor and non-adrenoceptor, imidazoline binding sites. We have examined the effect of agmatine at alpha 2-adrenoceptor binding sites and pre- and postjunctional alpha 2-adrenoceptors. Agmatine produced a concentration-dependent inhibition of 1 nmol/l 3H-clonidine binding to both rat (pKi-5.10 +/- 0.05) and bovine (pKi-4.77 +/- 0.38) cerebral cortex membranes. However, agmatine (0.1-100 microM) failed to activate pre-junctional alpha 2-adrenoceptors regulating transmitter release in the guinea-pig isolated ileum and rat isolated vas deferens, nor did it activate postjunctional alpha 2-adrenoceptors of the porcine isolated palmar lateral vein which mediate contraction or inhibition of forskolin-stimulated cyclic AMP formation. High concentrations of agmatine (10-30-fold the pKi at alpha 2-adrenoceptor binding sites) failed to influence alpha 2-adrenoceptor activation by either clonidine or UK-14304 (5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate) in any of the peripheral preparations examined. Moreover, even in a preparation where an interaction with alpha 2-adrenoceptor binding sites on cell membranes can be demonstrated, the rat cerebral cortex, agmatine failed to inhibit forskolin-stimulated cyclic AMP in the intact tissue or affect the inhibition produced by the selective alpha 2-adrenoceptor agonist UK-14304. Agmatine was also devoid of agonist activity in two preparations, the rat isolated thoracic aorta and the rat isolated gastric fundus, in which CDS has been reported to produce non-adrenoceptor effects. Thus, we have confirmed that agmatine recognizes alpha 2-adrenoceptor binding sites and, therefore, is a CDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

Plastic-covered metallic endoprostheses in the management of oesophageal perforation in patients with oesophageal carcinoma.

OBJECTIVE: To evaluate the role of plastic-covered self-expanding metallic endoprostheses in patients with oesophageal perforation occurring during endoscopically guided dilatation prior to laser treatment for malignant obstruction. SUBJECTS AND METHODS: Six patients with oesophageal perforation following laser treatment for malignant obstruction were treated. Four patients received the polyurethane-covered Wallstent endoprosthesis (Schneider SA, Bulach, Switzerland) and two patients the barbed polyethylene-covered Gianturco stent (William Cook, Europe). RESULTS: All patients had successful stent placement under intravenous sedation and fluoroscopic guidance with immediate relief of dysphagia and sealing of the perforation. Following the procedure all patients could eat either a normal diet or soft food and five patients were discharged within 3-4 days. None of the serious sequelae usually associated with oesophageal perforation were observed. Two patients required second overlapping stents to be inserted within 1 week because of minor migration of the initial endoprostheses. In one patient two stents were necessary because the carcinoma extended over 17 cm. Five patients died after stent insertion (mean survival time = 49 days, range 16-80; median survival time = 37 days, range 16-80) due to a general deterioration in their condition, although all could swallow normally until death. The remaining patient was well and tolerating a light diet at 1 month. CONCLUSION: This technique is quick, safe and cost-effective and is now our preferred method of managing malignant oesophageal obstruction associated with perforation.

Aged↗

Expression of pulmonary surfactant protein D in rat gastric mucosa.

Gastric mucosa is protected from an acidic lumenal environment by an extracellular layer composed in part of phospholipids that are similar in composition to the phospholipids of lung surfactant. The function and metabolic processing of lung surfactant is regulated, in part, by surfactant specific proteins. We speculated that the gastric extracellular acid barrier might be regulated by such proteins. We demonstrate by RNA blot analysis, RT-PCR, and immunostaining and protein blot the synthesis of surfactant protein D (SP-D) in mucus-secreting cells of the gastric mucosa. SP-D protein and mRNA were not detected in the duodenum and the remainder of the gastrointestinal tract. We speculate that SP-D may participate in the regulation of secretion or assembly of the gastric acid barrier. Alternatively, SP-D may participate in gastric mucosal host defense.

Animals↗

Combined bile acid therapy is more effective on biliary lipids and dissolution rates than monotherapy after gallstone lithotripsy.

BACKGROUND: Accurate sampling of gallbladder bile for biliary analysis is essential for determining any potential difference between combined bile acid therapy and monotherapy in gallstone patients. METHODS: In 104 gallstone patients undergoing extracorporeal shock wave lithotripsy with following bile acid therapy [either chenodeoxycholic acid (500 mg/day) and ursodeoxycholic acid (500 mg/day), group I (n = 53), or ursodeoxycholic acid alone (1000 mg/day), group II (n = 51)], bile samples, obtained by direct fine needle puncture of the gallbladder, were investigated for biliary lipids, total biliary protein concentration, and nucleation time before and after 12 months of bile acid therapy. RESULTS: Initially, a negative correlation was found between nucleation time and number of gallstones and between total biliary protein concentration and nucleation time (r = -0.52 and r = -0.49 in group I vs r = -0.56 and r = -0.51 in group II, p < 0.01 in each group). The correlation between total biliary protein concentration and nucleation time was also found after 12 months of bile acid treatment (r = -0.54 in group I vs r = -0.47 in group II, p < 0.01 in each group). In group I, the decrease in cholesterol saturation index, biliary cholesterol, cholic acid, deoxycholic acid, and total protein concentration was more pronounced than in group II (p < 0.01). The same effect was found concerning the prolongation of nucleation time (p < 0.01). Furthermore, dissolution rates were higher in group I compared with group II (80.4 vs 69.0%, p < 0.01). CONCLUSION: In gallstone patients, combined therapy with urso- and chenodeoxycholic acid is superior to either ursodeoxycholic acid alone or biliary parameters in bile samples obtained by direct fine needle puncture of the gallbladder.

Bile↗

Identification of futility in intensive care.

Rising costs of intensive care and the ability to prolong the life of critically ill patients creates a need to recognise early those patients who will die despite treatment. We used changes in a modified APACHE II score (organ failure score) to make daily predictions of individual outcome in 3600 patients. 137 patients were predicted to die and of these, 131 (95.6%) died within 90 days of discharge from hospital (sensitivity 23.4%, specificity 99.8%); a false-positive diagnosis rate of 4.4%. 2 of the 6 survivors have subsequently died but 4 are alive with good quality of life. Patients predicted to die stayed 1492 days in intensive care and incurred 16.7% of total intensive care expenditure and 46.4% of the cost of all patients that died. Median survival after a prediction to die was 2 days, accounting for 62% of intensive care patient days in this patient group, giving an effective intensive care cost per survivor of UK 129,651 pounds. If used prospectively, this algorithm has the potential to indicate the futility of continued intensive care but at the cost of 1 in 20 patients who would survive if intensive care were continued.

APACHE↗

Tau-mutant hamster SCN clock neurones express a 20 h firing rate rhythm in vitro.

In vitro neurophysiological studies have demonstrated a circadian rhythm with a period of 24 h in spontaneous neuronal discharge frequency within the rodent suprachiasmatic nucleus (SCN) circadian clock. This report examines the 'circadian' firing rate rhythm in the SCN of the homozygous Tau-mutant Syrian hamster which expresses a short period behavioural rhythm. The spontaneous SCN neuronal firing rate patterns are similar to those observed in wild types. The Tau SCN firing rate rhythm displays a peak in neuronal activity occurring 5-6 h before the predicted onset of wheel-running activity, with a peak-to-peak period of 20 h. This period of the rhythm of spontaneous neuronal discharge within the Tau-mutant SCN parallels the behavioural free-running period of 20 h.

Action Potentials↗