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Biomedical subjects

A J Bellingham

Publications and source records attributed to A J Bellingham.

At least 55 records · Page 3Linked to original sources
PubMed1986

Normal levels of ATP, total nucleotides and activities of three enzymes related to nucleotide metabolism in fetal erythrocytes.

Pure fetal blood was obtained by direct-vision fetoscopy from 30 fetuses at 17-23 weeks gestation. The erythrocyte concentrations of ATP and total nucleotides and the activities of the enzymes pyrimidine-5'-nucleotide nucleosidase (Pyr5N), phosphoribosylpyrophosphate (PRPP) synthetase and adenylate kinase (AK) were analysed by established techniques to find the normal ranges for this gestational age. The ranges were relatively narrow and could serve as reference values for the prenatal diagnosis of defects in nucleotide metabolism. The results from the fetal erythrocytes were compared with the corresponding values from the maternal blood collected and analysed concurrently. The ATP and total nucleotide concentrations and the activity of Pyr5N in the fetal cells were substantially higher than those of the maternal blood. The activities of PRPP synthetase and AK were much lower. The significance of these findings is discussed.

5'-Nucleotidase↗
PubMed1985

The relative sensitivity of peripheral blood T-lymphocyte colony forming cells and bone marrow CFU-GM to deoxyadenosine and 2'deoxycoformycin.

The effects of the nucleoside deoxyadenosine (AdR) towards 2'deoxycoformycin (dCF) treated peripheral blood T-lymphocyte and bone marrow myeloid progenitor cells has been studied. Mononuclear cell preparations were exposed to dCF and AdR in suspension culture prior to washing and culture in a medium free of exogenous nucleosides. The combination of dCF and AdR was found to be highly toxic to peripheral blood T lymphocyte colony forming cells (CFU-TL) following prolonged (18 h) incubation. CFU-GM were markedly less sensitive to the combination of dCF and AdR, concentrations of dCF (10(-5) M) and AdR (10(-5) M) which produced an almost total inhibition of CFU-TL only inhibited CFU-GM by a mean of 10%.

Adenosine Deaminase Inhibitors↗
PubMed1985

The use of danazol in the management of chronic immune thrombocytopenic purpura.

Danazol has recently been reported to be an effective mode of treatment for patients with refractory immune thrombocytopenic purpura. Following a 3 month trial of danazol, only one of 10 patients experienced a sustained increase in platelet counts and two other patients had a transient improvement. While the drug was well tolerated, it does not appear to be particularly helpful in the management of these patients.

Adult↗
PubMed1985

Red cell metabolism in renal failure--the effect of dialysis.

The mechanism of the increased haemoglobin (Hb) and erythrocyte survival in continuous ambulatory peritoneal dialysis (CAPD) compared to haemodialysis (HD) was investigated by measuring hexose monophosphate shunt (HMP) activity and reduced glutathione concentration (GSH) in 12 patients--six patients who were stable on CAPD, and six patients who were stable on HD, and also six normal controls. We confirmed the rise in haemoglobin in the CAPD group. The HMP activity, measured by the liberation of 14CO2 from radioactive glucose labelled at the C1 position shows that both HD and CAPD groups fall into the normal range (normal 3-11%) although the HMP activity is higher in the HD group. The reduced glutathione concentration in the three groups was: normal controls 2.41 +/- 0.19 mmol/l; HD 3.31 +/- 0.43 mmol/l; CAPD 2.68 +/- 0.24 mmol/l. The HD group is significantly higher (P less than 0.01) than both normal and CAPD. We conclude that the rise in haemoglobin in CAPD patients is not related to a more effective HMP. This suggests other mechanisms i.e. marrow function or red-cell loss in HD may be the reason for the lower haemoglobin in this group.

Cell Count↗
PubMed1984

The effects of therapeutic dialysis and renal transplantation on uraemic serum inhibitors of erythropoiesis in vitro.

The methyl cellulose culture system using human bone marrow and erythropoietin (Ep) at different concentrations was used to examine the effects of uraemic sera on erythropoiesis in vitro. Sera from undialysed patients with advanced uraemia (plasma creatinine greater than 900 mumol/l) when added to cultures at 10% with Ep at 2.0 u/ml were consistently inhibitory to the growth of erythroid burst-forming units (BFU-E). No inhibition of erythroid colony-forming units (CFU-E) was observed at this Ep concentration but inhibition was consistently demonstrated with Ep at 0.2 u/ml. Sera from undialysed patients with less severe uraemia (plasma creatinine less than 900 mumol/l) were not inhibitory to BFU-E or CFU-E at Ep 2.0 u/ml. Sera from patients with stable, functioning renal transplants were stimulatory to erythropoiesis in vitro with Ep at 2.0 u/ml. This finding is consistent with the normal or increased haematocrits often found following renal transplantation. Sera from patients on maintenance haemodialysis and continuous ambulatory peritoneal dialysis (CAPD) were not significantly different from normal in their effect on BFU-E growth in vitro and were slightly but significantly stimulatory to the growth of CFU-E. This suggests that these two forms of dialysis are equally effective in reducing the activity of uraemic inhibitors in serum and that inhibition of the marrow response to Ep and/or burst-promoting activity (BPA) is unlikely to be a major factor in the continued anaemia of dialysis patients.

Bone Marrow Cells↗
PubMed1984

Parvovirus infection in a family associated with aplastic crisis in an affected sibling pair with hereditary spherocytosis.

There have been many reports of aplastic crisis preceded by a febrile illness in hereditary haemolytic anaemias. Recent research has shown that the human parvovirus may be a causative agent. We report on an adult sibling pair with hereditary spherocytosis who presented in aplastic crisis after a febrile illness. Both had evidence of recent parvovirus infection, shown by the presence of IgM class specific antibody in their sera. The children of one of the sibling pair, one of whom has hereditary spherocytosis but no chronic haemolysis, showed similar evidence of acute parvovirus infection.

Adult↗
PubMed1983

Separation of glycosylated haemoglobins using immobilized phenylboronic acid. Effect of ligand concentration, column operating conditions, and comparison with ion-exchange and isoelectric-focusing.

Haemoglobins from diabetic and non-diabetic individuals have been separated by affinity chromatography using immobilized phenylboronate, which interacts specifically with diol-containing compounds such as glycosylated haemoglobin. The effects of ligand concentration, flow rate, column geometry, preincubation of sample, buffer composition and temperature have been investigated. Significant correlation was found between results from affinity-chromatography and ion-exchange and isoelectric-focusing methods. Isoelectric-focusing of the haemoglobin fractions obtained from affinity chromatography indicate that, in addition to haemoglobin A1c, some haemoglobin A is also bound to immobilized phenylboronic acid. Assays of haemolysates obtained from red blood cells incubated in glucose solutions suggest that unstable pre-(haemoglobin A1c) does not interfere. The assay is not affected by the presence of haemoglobin F.

Boronic Acids↗
PubMed1983

Ceftazidime compared to tobramycin and ticarcillin in immunocompromised haematological patients.

Tobramycin and ticarcillin has been compared to ceftazidime in a clinical study on immunocompromised patients with febrile episodes. In the tobramycin and ticarcillin group (A) 70 febrile episodes occurred (10 being unassessable) in 43 patients of which 16 (23%) were bacteriologically positive. Forty-three episodes occurred during neutropenia. In the ceftazidime group (B) 54 febrile episodes (6 being unassessable) were treated in 34 patients. Eleven (20%) were bacteriologically positive and 30 episodes occurred during neutropenia. Clinical cure in group A occurred in 39 episodes, 65% of assessable cases. Cures in group B numbered 27 out of 54 episodes (56% of assessable cases). Clinical failure among evaluable cases, that is no decrease in fever in three days, was 22% in group A and 31% in group B. These results, within the limitation of the study, suggest that ceftazidime given alone at a dosage of 1 g tds is not significantly worse than tobramycin 120 mg tds plus ticarcillin 2 g tds.

Bacterial Infections↗
PubMed1983

Haemoglobin concentration and serum erythropoietin in renal dialysis and transplant patients.

In patients with chronic renal failure the use of the relatively new dialysis technique of continuous ambulatory peritoneal dialysis (CAPD), unlike other forms of dialysis, is consistently associated with an increase in Hb concentration, but the mechanism remains obscure. We measured Hb, haematocrit, S-erythropoietin and Hb-oxygen affinity in 3 groups of patients with chronic renal failure. (1) Untreated patients starting on haemodialysis. (2) Patients on intermittent peritoneal dialysis changing to CAPD. (3) Patients from the above 2 groups receiving renal transplants. In addition, red cell mass, plasma volume and red cell survival were measured in (2), before starting CAPD and at 6 months. There were distinctly different patterns of change in Hb concentration, Hb-oxygen affinity and S-erythropoietin in the 3 groups of patients. The increase in Hb concentration with CAPD is due to both a fall in plasma volume and an increase in red cell mass, with an increase in red cell survival. There was no change in Hb-oxygen affinity or serum erythropoietin concentration. The improvement in red cell mass and survival may be related to increased clearances of substances with mol. wt.s between 500 and 5000 daltons which accumulate in renal failure (uraemic middle molecules).

Erythropoietin↗
PubMed1983

Hyaline-vascular variant of angiofollicular lymph node hyperplasia with systemic manifestations and response to corticosteroids.

We report two cases of angiofollicular lymph node hyperplasia of the hyaline-vascular type. The patients were atypical in having systemic complications, which are much more commonly seen in the plasma cell variant of this disorder. In each case, the diagnosis was established some years after the initial presentation. Both patients presented with unusual systemic manifestations. The exact mechanism underlying the associated features is unknown, but these cases provide some evidence that the disease is primarily a vascular proliferative or inflammatory disorder. All manifestations of the disease responded to the administration of prednisolone with rapid reduction of dosage to less than 10 mg daily. Maintenance therapy may be required to prevent relapse.

Adult↗
PubMed1982

Erythrocyte metabolism in patients on haemodialysis and continuous ambulatory peritoneal dialysis.

1. Erythrocyte metabolism was investigated and glycolytic intermediates were measured in nine patients with chronic renal failure who were subsequently treated with haemodialysis. The same investigations were performed in nine patients on continuous ambulatory peritoneal dialysis (CAPD) who had previously been treated with intermittent peritoneal dialysis (IPD) (eight patients) or dietary restriction (one patient). 2. The patients who received haemodialysis had a partially compensated metabolic acidosis before treatment. With haemodialysis, plasma phosphate (Pi) fell and base excess, erythrocyte 2,3-diphosphoglycerate (2,3-DPG), glucose consumption and lactate production rose significantly. In this group the most important influence on erythrocyte metabolism was base excess. The pattern of erythrocyte glycolytic intermediates showed that the rise in 2,3-DPG with haemodialysis was brought about within the Rapoport-Luebering shunt; there was no statistically significant decrease in haemoglobin-oxygen affinity. 3. The patients who received CAPD were not acidotic before starting this form of treatment. With CAPD, there was a significant increase in haemoglobin and fall in plasma phosphate, erythrocyte 2,3-DPG and glucose consumption. The major factors influencing erythrocyte metabolism in this group were plasma phosphate and haemoglobin concentration. The fall in 2,3-DPG was produced by inhibition of 6-phosphofructokinase (EC 2.7.1.11); despite this fall, haemoglobin-oxygen affinity was not affected.

2,3-Diphosphoglycerate↗
PubMed1981

Bioluminescent assay of adenine nucleotides: rapid analysis of ATP and ADP in red cells and platelets using the LKB luminometer.

The assessment of both red cell and platelet function requires assay of adenine nucleotides. We describe the use of the new LKB luminometer to measure adenosine triphosphate (ATP) and adenosine diphosphate (ADP) by bioluminescence in both normal and abnormal red cells and platelets. ATP was measured a in a lysate of red cells suspended in buffer, pH 7.4, b in ethanol extracts of platelets from platelet-rich plasma (PRP) and c in ethanol extracts of supernatant platelet-poor plasma (PPP) following platelet aggregation by collagen. ADP was measured as ATP after phosphorylation by pyruvate kinase (PK) with phosphoenolpyruvate (PEP). Duplicate assays showed a variance of less than 3%. Red cell lysates and ethanol extracts of PRP and PPP stored at -40 degrees C were stable for 4 weeks. Duplicate assays of ATP and ADP in eight samples plus standards could be performed in 2 h. Normal values were: red cells (microM/ml red cells) (n = 20), ATP 1.15 +/- 0.17 (1 SD), ADP 0.22 +/- 0.07, ATP/ADP (mean ratio) 5.76:1, platelets (nm/10(9) platelets) (n = 20), ATP 53.3 +/- 7.6, ADP 27.8 +/- 5.8, ATP/ADP (mean ratio: 1.96:1). Abnormalities of red cell ATP and/or ADP could be demonstrated in chronic renal failure, hereditary glycolytic enzyme deficiencies and other haemolytic states. In myeloproliferative disorders defective platelet aggregation associated with storage pool deficiency and/or impaired release of ADP and ATP could be shown. We conclude that this is a reliable, rapid and economical technique for measuring red cell and platelet adenine nucleotides.

Adenosine Diphosphate↗