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Biomedical subjects

W D Rees

Publications and source records attributed to W D Rees.

At least 73 records · Page 4Linked to original sources
PubMed1988

Neural regulation of duodenal alkali secretion: effects of electrical field stimulation.

The role of transmitters released from enteric neurons in regulating bicarbonate secretion by the proximal duodenum has been studied using electrical field stimulation (EFS). Stripped duodenal mucosa from Rana catesbeiana was mounted as an intact tube over circular platinum electrodes, and luminal alkalinization was measured by pH stat titration before, during, and after EFS. Transmucosal potential difference (PD) was simultaneously measured before and after EFS by paired electrodes. Square-wave pulses 50 V, 2 ms in duration, at 10 Hz were delivered in trains of 0.5 s at 1 Hz for periods of 15 min after stable basal secretion. This resulted in a 63 +/- 27% increase in alkalinization that returned to basal values after cessation of the stimulus, without change in transmucosal PD. Serosal-to-lumen [3H]mannitol flux was not affected. Repetition of the stimulus resulted in similar responses for as long as the tissue remained viable. The response to EFS was abolished by tetrodotoxin (10(-6) M) and veratrine (0.1 mg/ml), indicating that intrinsic neurons were responsible for mediating the effect. In addition, the effect was blocked by serosal dinitrophenol (10(-4) M), indicating that the secretory response occurred by a metabolically dependent process. These results indicate that alkalinization by proximal duodenum may be controlled by neurotransmitter release from local enteric neurons.

Animals↗
PubMed1987

Binding of cytochalasin B to trypsin and thermolysin fragments of the human erythrocyte hexose transporter.

The cleavage of the human erythrocyte hexose transporter by the proteinases trypsin and thermolysin has been studied. When red cell membranes are treated with trypsin, washed and then photolabelled with cytochalasin B, a labelled peak at 18 kDa is obtained. This labelling of the cleaved transporter is D-glucose inhibitable. This probably indicates that the residual 36 kDa portion of the transporter is not required for binding of ligands. Extensive cleavage of the transporter with low concentrations of thermolysin only occurs when transporter is prelabelled with cytochalasin B. This indicates that covalently bound cytochalasin B can cause a conformational change which exposes the thermolysin cleavage site.

Binding Sites↗
PubMed1987

Photolabelling of the hexose transporter at external and internal sites: fragmentation patterns and evidence for a conformational change.

The human erythrocyte sugar transporter has been labelled at its internal site with cytochalasin B and at its outside site by the azidosalicoyl derivative of bis(D-mannose) (ASA-BMPA). The cleavage of the transporter by various proteinases has been studied. Chymotrypsin, subtilisin and V8 proteinase give parallel fragmentation patterns for the two labels down to fragments as small as 7 kDa. Thus the binding sites for the two labels can only be separated by a small span of protein. 2-Nitro-5-thiocyanobenzoic acid (NTCB) cleaves at cysteines to give a 15 kDa fragment from the two labels. N-Bromosuccinimide (a reagent which preferentially cleaves at tryptophan residues) has revealed differences in fragmentation of the transporter labelled with either cytochalasin B or with ASA-BMPA. A major cleavage site is proposed to occur at tryptophan 186 which leaves a C-terminal fragment containing both labels. A tryptophan cleavage at residue 388 divides the cytochalasin B site and the ASA-BMPA site. A further tryptophan cleavage gives a cytochalasin B labelled 3 kDa fragment probably from residues 388-412. This gives an assignment of the cytochalasin B site as the inside of the hydrophobic span H 10. Since the ASA-BMPA site is probably only 7 kDa from residue 388 and is on the same 15 kDa NTCB fragment as cytochalasin B we assign this to the outside of hydrophobic span H 9. Thermolysin only cleaves the transporter labelled with cytochalasin B and not with ASA-BMPA. A 18 kDa cytochalasin B labelled fragment is formed. This is indicative of a change in conformation of the transporter when an outside ligand is bound such that the inside of the hydrogen bonding transmembrane segments H 7 and H 8 (and containing the proposed thermolysin cleavage site) are withdrawn from the cytosolic surface. Thus it appears that the core of the transporter (including the external and internal sites plus the transmembrane channel) is located between segments H 7 and H 10.

Affinity Labels↗
PubMed1987

Re-examination of hexose-transporter inhibition and labelling by hexose isothiocyanates.

We have re-examined hexose-transport inhibition by hexose isothiocyanates and find that the inhibition is incomplete, probably because of decomposition of the reagent. The inhibition type is 'mixed', because hexose-transporter ligands such as maltose and cytochalasin B only give partial protection from inhibition. This suggests that a liganded-transporter-hexose isothiocyanate ternary complex is formed. We have compared the labelling of red-blood-cell membranes by [14C]MITC (D-maltose isothiocyanate) with the labelling obtained using a photoaffinity probe (ASA-BMPA [2-N-(4-azidosalicyloyl)-1,3-bis-(D-mannos-4'-yloxy)-2 -propylamine]) which gives specific labelling of the hexose transporter in band 4.5. [14C]MITC gives a partially D-glucose-displaceable labelling of a band 3 component in the same cell preparations which show ASA-BMPA labelling of band 4.5. This eliminates the possibility that band 4.5 labelling can only occur when the HITC (hexose isothiocyanate) binding protein in band 3 is proteolysed. HITC pretreatment does not decrease ASA-BMPA labelling of the exofacial site of band 4.5. This is also consistent with the formation of ternary complex. However, HITC pretreatment inhibits both reversible and photoactivated covalent [3H]cytochalasin B binding to band 4.5. These results suggest that, in the intact cell, interactions between a band 3 HITC-binding component and the inside cytochalasin B-binding site on the hexose transporter in band 4.5 may occur.

Affinity Labels↗
PubMed1987

Effect of naloxone on the antral motor response to solid food in man.

Antroduodenal motor activity was recorded in eight healthy subjects using perfused tubes connected to external strain gauge transducers. Each subject was studied over a 2.5-h period following ingestion of a solid meal, on 2 separate days. Intravenous saline was administered on one day and saline plus naloxone (40 micrograms kg-1 h-1) on the other, in randomized order. Naloxone markedly inhibited the antral motor response to food and this effect was due to decreased amplitude and contractile frequency. The duodenal motor response to solid food and the postprandial rise in serum gastrin and plasma pancreatic polypeptide were not altered by naloxone. These observations suggest that peripheral or central opiate receptors play a role in regulating the antral motor response to food.

Adult↗
PubMed1987

Effect of luminal pH on the output of bicarbonate and PGE2 by the normal human stomach.

The gastric output of bicarbonate and prostaglandin E2 has been calculated using a perfusion technique before and after instillation of 100 mM hydrochloric acid into the stomach of seven healthy volunteers. A significant increase in bicarbonate output occurred from 258 +/- 38 mumol/30 min during the basal period to 531 +/- 86 mumol/30 min after return of the intragastric pH to neutral (p less than 0.05). Prostaglandin E2 output also increased significantly from 410 +/- 136 pmol/30 min to 1002 +/- 194 pmol/30 min (p less than 0.05). The changes were caused mainly by an increase in gastric secretory volume with only non-significant increases in concentrations of bicarbonate and prostaglandin E2. The results suggest that mechanisms exist to adjust the rate of gastric bicarbonate secretion to the prevailing intraluminal pH and that this may occur through the release of prostaglandin E2.

Adult↗
PubMed1987

Evaluation of the hydrogen breath test in man: definition and elimination of the early hydrogen peak.

After ingestion of a non-absorbable carbohydrate breath hydrogen excretion increases early at about 10 minutes, and again later when the ingested carbohydrate enters the caecum. The late rise has been used as a marker of mouth to caecum transit time, but the source of the early rise has not been satisfactorily explained. We studied in 60 healthy volunteers the source and frequency of the early rise in breath hydrogen after ingestion of a non-absorbable carbohydrate. After ingestion of either lactulose solution (10 g in 150 ml water), lentil soup (46 g carbohydrate) or solid meal containing baked beans (15 g carbohydrate), breath hydrogen was significantly raised above basal concentrations within 10 minutes (81 +/- 27, 395 +/- 138 and 110 +/- 52% above basal respectively). A significant rise in breath hydrogen (75 +/- 21%) occurred 10 minutes after sham lactulose feeding (lactulose applied to oral cavity but not swallowed), but no early peak occurred after sham saccharin feeding (non-fermentable carbohydrate), intragastric or intraduodenal administration of lactulose. Ten of the 12 subjects given lactulose sham feeding were restudied after oral hygiene with chlorhexidine mouthwash. In these the early hydrogen peak was abolished. Oral hygiene also reduced the occurrence and magnitude of the early hydrogen rise after lactulose ingestion. These findings indicate that the early rise in breath hydrogen observed after ingestion of lactulose is produced by interaction with oral bacteria.

Adolescent↗
PubMed1987

Simultaneous measurement of in vitro gastroduodenal prostaglandin E2 synthesis and degradation in peptic ulcer disease.

The ability of mucosal specimens from the stomach and duodenum to synthesize and degrade prostaglandin E2 has been determined in normal subjects and peptic ulcer patients. Significant reduction in fundic PGE2 synthesis capacity was observed in gastric ulcer patients. There was also significant reduction in the PGE2 degradation capacity of antral, fundic, and duodenal mucosal specimens in gastric ulcer patients. Patients with gastritis showed significant elevation of both antral and fundic PGE2 synthesis capacity compared with normal but no alteration in PGE2 degradation. No differences were observed in PGE2 synthesis and degradation rates in patients with duodenal ulcer. The results argue in favour of an association between impairment of PGE2 metabolism in the mucosa of patients with gastric but not duodenal ulceration.

Adult↗
PubMed1987

Effect of sucralfate on gastroduodenal bicarbonate secretion and mucosal prostaglandin E2 metabolism.

The effect of sucralfate on gastroduodenal bicarbonate secretion has been examined using isolated amphibian mucosa. Significant increases in gastric bicarbonate secretory rate were seen following addition of 0.5 milligram sucralfate to the luminal solution. Duodenal alkali secretion was stimulated only by a higher concentration of 1 milligram. Pretreatment with indomethacin prevented the increases in gastric and duodenal bicarbonate secretion observed after sucralfate. Other experiments indicated that sucralfate caused stimulation of prostaglandin E2 formation by mucosal homogenates. These studies demonstrate that sucralfate is a potent stimulant of gastroduodenal bicarbonate secretion and that the action is dependent on mucosal prostaglandin formation. These effects are likely to play an important role in the mode of action of the drug.

Animals↗
PubMed1987

Changes in prescribing for terminal care patients in general practice, hospital and hospice over a five-year period.

Differences in prescribing between 1981 and 1986 were examined for 100 terminal care patients admitted to a city hospice in each year. Prescribing before and after the patients were admitted to the hospice was also compared for the two years. Between 1981 and 1986 there was a large increase in the number of patients receiving morphine sulphate tablets and a reduction in the numbers receiving Brompton's mixture and other unsuitable analgesics both before and after admission. Contrary to critical opinion, general practitioners showed more acceptable prescribing patterns in both years than hospital doctors. In the hospice more patients received non-narcotic analgesics and parenteral diamorphine by syringe driver in 1986 than in 1981. The need for an organized system of postgraduate training in terminal care is considered.

Adult↗
PubMed1986

Influence of opiates on alkali secretion by amphibian gastric and duodenal mucosa in vitro.

Experiments were performed to study the effects of opiates on gastric and duodenal alkali secretion in amphibian mucosa in vitro. Alkali secretion by fundic mucosa of Rana temporaria, or antral mucosa of Rana catesbeiana, was unaffected by morphine, methionine-enkephalin and leucine-enkephalin, two enkephalin analogues, or the opiate antagonist naloxone. Acid secretion by fundic mucosa in vitro was not influenced by 10(-5) and 10(-4) M morphine, or by 10(-7) to 10(-5) M naloxone. However, duodenal alkali secretion in Rana catesbeiana was stimulated by opiates while the electrical potential difference was unaffected. Morphine stimulated secretion, maximally at 10(-5) M, by 33% over basal values, 30 min after exposure to the drug, whereas the maximal response to methionine-enkephalin occurred at 10(-6) M and was obvious within the first 15 min after administration. The effects of these opiates were prevented by pretreatment with naloxone or with the more specific opiate receptor antagonist ICI 154129. The response to morphine was inhibited when bicarbonate in the nutrient-side solution was replaced by the impermeant anion HEPES or by removal of chloride from the bathing media. Furosemide (10(-3) M) also inhibited the response of duodenal mucosa to morphine. The nerve-blocker tetrodotoxin (10(-7) M) prevented the morphine-induced response. These data suggest that opiates can stimulate duodenal alkali secretion, probably by activating an electrically neutral Cl-/HCO3- exchange. It seems likely that the effect of opiates is mediated by a neurologic intermediary, and the results suggest the possibility that duodenal alkali secretion may be under some neurologic control.

Alkalies↗
PubMed1986

Effect of certain ulcer-healing agents on amphibian gastroduodenal bicarbonate secretion.

The effect of luminal application of aluminum sulphate, sucralfate, and bismuth subcitrate on gastroduodenal alkali secretion has been studied with isolated amphibian mucosa. The mucosa, stripped of its external muscle layer, was mounted in chambers that allowed titration of alkali secretion and measurement of transmucosal potential difference and electrical resistance. Neutral aluminum sulphate (3 X 10(-3) M) increased bicarbonate secretion by fundic (mean +/- SEM = 144 +/- 48%, n = 5, P less than 0.05), antral (mean +/- SEM = 214 +/- 63%, n = 4, P less than 0.05), and duodenal (mean +/- SEM = 133 +/- 44%, n = 6, P less than 0.005) mucosa. Sucralfate (0.5 g/l) stimulated fundic (mean +/- SEM = 183 +/- 87%, n = 4, P less than 0.05) and antral (mean +/- SEM = 156 +/- 58%, n = 5, P less than 0.005) alkali secretion and, at a concentration of 1 g/l, duodenal output (mean +/- SEM = 42 +/- 15%, n = 6, P less than 0.05). Bismuth subcitrate (10(-4) M) produced a significant rise in fundic (mean +/- SEM = 80 +/- 21%, n = 5, P less than 0.05) and duodenal (mean +/- SEM = 62 +/- 7%, n = 6, P less than 0.05) alkali secretion. None of these agents altered transmucosal potential difference or electrical resistance. The actions of these agents on gastroduodenal bicarbonate secretion may be important in their ulcer healing effects.

Alum Compounds↗
PubMed1986

Immigrants and the hospice.

This is the first published report on immigrants and hospices. From 1979 to 1985 St Mary's cared for 74 European, Afro-caribbean and Asian immigrants. Immigrants referred to the Hospice were more likely to be accepted for care than indigenous patients. Women from the Indian sub-continent (mean age 42 years) were the youngest immigrants needing hospice care. European immigrants were older and more likely to receive hospice care than other immigrants.

Age Factors↗