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Biomedical subjects

G R Barclay

Publications and source records attributed to G R Barclay.

82 records · Page 5Linked to original sources

Frozen lymphocyte pools as technical and reference controls for lymphocyte transformation.

Healthy individuals' peripheral blood lymphocytes show wide ranges of response to mitogens and allogeneic lymphocytes. When individuals' lymphocytes are pooled together, the responses of the pool are equivalent to the means of the responses of the lymphocytes which comprise the pool. Pooled lymphocytes retain their responsiveness when stored frozen, and may be used as standard responding cells in lymphocyte transformation tests, but are not suitable controls for antigen-induced lymphocyte transformation.

Antigens↗

Leucocyte function in a case of chronic benign neutropenia of infancy associated with circulating leucoagglutinins.

A case of chronic benign neutropenia is described in association with circulating leucoagglutinins. IgG and IgM leucoagglutinins demonstrated by Sephadex G-200 chromatography agglutinated neutrophils and monocyte enriched leucocyte preparations. Total IgG, IgA, IgM and IgE, total haemolytic complement, C3 and C4 complement components were all within normal limits. Lymphocyte populations and transformation were normal apart from a relative increase in the number of B lymphocytes. In vitro studies showed that the patient's monocytes responded in chemotaxis, phagocytosis and intracellular killing of S. aureus in a comparable fashion to that of control neutrophils. Although the patient's serum also agglutinated monocytes these findings do not exclude the possibility that leucoagglutinins may have aetiological significance in this disease. The study also emphasizes the versatility of the monocyte in benign neutropenia.

Agglutinins↗

The effect of transfer factor on neutrophil function in chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis with hypoparathyroidism in a 6-year-old-boy is described. In addition to defects of in vivo and in vitro correlates of delayed-type hypersensitivity to Candida albicans the child also had abnormalities of neutrophil function in terms of their capacity to respond by chemotaxis to a known attractant and to kill suspensions of C. albicans. Dialysable transfer factor was given on six occasions at intervals of between 26 and 45 days. Neutrophil chemotaxis (optimal conditions) was restored following each of the six injections, neutrophil chemotaxis (sub-optimal conditions) following five of the six injections and candidicidal capacity following four of the six injections. The effects of transfer factor were transient requiring repeated injections. The Candida delayed-type hypersensitivity skin test was restored to normal but lymphocyte transformation to Candida extract was not consistently positive following treatment. There was a slight clinical improvement following therapy. These abnormalities of neutrophil and lymphocyte function point to the complexity of chronic mucocutaneous candidiasis. The improvement in neutrophil chemotaxis and candidicidal capacity following treatment suggests that transfer factor may be a heterogeneous group of molecules, some of which affect granulocytes and restore defects in their function.

B-Lymphocytes↗

Aspects of influenza C virus replication.

Influenza C virus antigen could be detected by immunofluorescence in chick amniotic epithelium 4 hr. after inoculation with undiluted amniotic fluid. Antigen could be detected in the nucleus of rhesus monkey kidney tissue cultures 10 hr. after infection. Only cytoplasmic fluorescence was observed 17-21 hr. after infection.The pattern of replication was similar to that reported for group I myxoviruses, indicating that the virus is correctly classified as an influenza virus.

Amnion↗

The thermal polymerization of orosomucoid.

1. Orosomucoid was prepared from the urine of a nephrotic patient and polymerized by heating it in a range of salt concentrations at pH4.1. 2. Heating at low ionic strengths produced a ;chain' polymer of indefinite length but having the same width as the diameter of the monomer (5.0nm.). Similar treatment in high ionic strengths also produced a spherical (;ball') polymer of limited diameter (14.8nm.). 3. The size and shape of both polymers were determined from ultra-centrifuge, gel-filtration and electron-microscope results. The results suggest that eight monomer units condense to form the ball polymer. 4. Heating orosomucoid at pH1.8 hydrolysed the N-acetylneuraminic acid off the molecule; only chains could then be formed, even in high ionic strengths. 5. Both polymers were stable under normal conditions but could be depolymerized in 3m-guanidine hydrochloride. The monomer could be repolymerized on heating: the ;chain monomer' only formed chains at all ionic strengths, but the ;ball monomer' was indistinguishable from the original monomer in its immunological properties and polymerization reaction.

Chromatography, Gel↗

Effect of polymerized orosomucoid on some strains of influenza virus.

1. Polymers of orosomucoid were produced in two molecular shapes, filamentous (;chain') and spherical (;ball'), by heating the sodium salt of the monomer in either water or high concentrations of sodium chloride. An ;intermediate' state containing both shapes in various proportions was found in preparations obtained by polymerizing orosomucoid in intermediate concentrations of sodium chloride. 2. The filamentous form of polymer was found to inhibit strongly the haemagglutination of some (;sensitive') strains but not of other (;insensitive') strains of influenza virus; the ;intermediate' form feebly inhibited haemagglutination by ;sensitive' strains. 3. The filamentous form agglutinated both ;sensitive' and ;insensitive' strains of virus; the other forms of polymer did not. It also inhibited multiplication of both ;sensitive' and ;insensitive' strains when inoculated into embryonated and de-embryonated eggs. 4. The ;intermediate' and spherical forms of the polymer had no effect on the virus multiplication. 5. Polymers of orosomucoid from which neuraminic acid had been split off had no detectable effect on influenza viruses.

Agglutination Tests↗

Early increase in intestinal permeability in patients with severe acute pancreatitis: correlation with endotoxemia, organ failure, and mortality.

Sepsis accounts for 80% of deaths from acute pancreatitis. This study aimed to investigate early changes in intestinal permeability in patients with acute pancreatitis, and to correlate these changes with subsequent disease severity and endotoxemia. The renal excretion of enterally administered polyethylene glycol (PEG) 3350 and PEG 400 was measured within 72 hours of onset of acute pancreatitis to determine intestinal permeability. Severity was assessed on the basis of APACHE II scores and C-reactive protein measurements. Serum endotoxin and antiendotoxin antibodies were measured on admission. Eight-five patients with acute pancreatitis (mild in 56, severe in 29) and 25 healthy control subjects were studied. Urinary excretion of PEG 3350 (median) was significantly greater in patients who had severe attacks (0.61%) compared to those with mild disease (0.09%) and health control subjects (0.12%) (P <0. 0001), as was the permeability index (PEG 3350/400 excretion) (P <0. 00001). The permeability index was significantly greater in patients who subsequently developed multiple organ system failure and/or died compared with other severe cases (0.16 vs. 0.04) (P = 0.0005). The excretion of PEG 3350 correlated strongly with endotoxemia (r = 0.8; P = 0.002). Early increased intestinal permeability may play an important role in the pathophysiology of severe acute pancreatitis. Therapies that aim to restore intestinal barrier function may improve outcome.

APACHE↗

1997 Harry M. Vars Research Award. Does the route of feeding modify gut barrier function and clinical outcome in patients after major upper gastrointestinal surgery?

BACKGROUND: Direct experimental evidence suggests that total enteral nutrition (TEN) reduces septic morbidity compared with bowel rest and total parenteral nutrition (TPN) and that mucosal support and maintenance of gut barrier function is a key mechanism. This effect is supported indirectly by clinical studies, but this question has not previously been investigated directly in the postoperative patient. This study examined the hypothesis that early enteral feeding after major upper gastrointestinal surgery may modulate gut barrier function and decrease the risk of major infective complications compared with bowel rest and parenteral nutrition. METHODS: A randomized clinical trial of 67 patients (TPN = 34; TEN = 33) fed postoperatively for 7 days was performed. Thirty-day major morbidity and mortality were monitored. Intestinal permeability was measured using the lactulose/mannitol test preoperatively and on postoperative days 1 and 7. Systemic anti-endotoxin core immunoglobulin G and M antibodies and serum albumin and C-reactive protein were quantified at these time points. RESULTS: No clinical benefit was observed in patients fed enterally compared with the parenterally fed group. Intestinal permeability was increased on the 1st postoperative day in association with evidence of endotoxin exposure. By day 7, enteral feeding compared with parenteral feeding had failed to significantly influence any of the gut barrier or systemic parameters. CONCLUSIONS: This randomized controlled trial of TEN vs TPN after major upper gastrointestinal surgery failed to show a clinical benefit for the enteral route. Moreover, enteral nutrition did not modulate gut barrier function postoperatively.

Antibodies↗