Biomedical subjects
C H Beresford
Publications and source records attributed to C H Beresford.
Attitudes of Dunedin medical students to population carrier screening for cystic fibrosis.
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Gene testing in the childhood spinal muscular atrophies.
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The confirmation of preclinical familial antithrombin deficiency using polymorphism and specific oligonucleotide probes .
Familial deficiency of antithrombin causes venous thromboembolism which may not become clinically apparent until the third or fourth decade of life. In affected families conventional tests of antithrombin activity and antithrombin antigen levels may not be sufficiently accurate to discriminate with certainty between those young people who have inherited the abnormal gene and those who have not. Molecular probes for polymorphisms linked to the gene of interest may be informative but in some families are not. We have used the knowledge of the precise molecular defect in antithrombin Glasgow to design and manufacture DNA probes and have used these probes to detect the presence of the abnormal gene in DNA from clinically unaffected family members and thus confirm their inheritance of antithrombin deficiency and their predisposition to venous thromboembolic disease.
A DNA diagnostic service.
We describe the use of techniques of DNA analysis for the diagnosis of certain inherited diseases during life and in the prenatal period, and for the diagnosis of some infectious diseases. Most local and some national needs for predictive genetic testing have been met. The costs of establishing our service are presented and are compared with those of similar services recently established in the United Kingdom. In the 12 month period described, running costs were approximately $57,000 and salaries for the two scientific officers and the medical technologist required to run the service were $97,000. The prerequisites for the successful running of such a service are discussed.
Antithrombin Glasgow, 393 Arg to His: a P1 reactive site variant with increased heparin affinity but no thrombin inhibitory activity.
Antithrombin Glasgow is a hereditary abnormal antithrombin that has lost thrombin inhibitory activity. It was isolated from the plasma of a 41-year-old male with a history of thrombotic events. Antithrombin Glasgow was purified from plasma using heparin-Sepharose chromatography at pH 7.4 eluting with increasing concentrations of NaCl. The normal protein eluted with 0.9 mol/l NaCl and Glasgow with 1.05 mol/l NaCl. Electrophoresis in agarose at pH 8.6 showed the variant to migrate more anodally than normal. The C-terminal small fragment resulting from catalytic cleavage with elastase between P3 and P4 of the reactive loop was isolated and sequenced. This showed the replacement of the arginine at residue 3 by a histidine. This is residue 393 in the intact molecule. The findings suggest that heparin, on binding, interacts indirectly with the reactive centre region of antithrombin.
Cytomegalovirus infection and blood transfusion.
The incidence of cytomegalovirus antibody positivity has been determined in populations of blood donors in centres in the North and South Islands of New Zealand. No difference in incidence was found. Rates of antibody detection increased from approximately 30% in younger donors to approximately 65% in donors between the ages of 56 and 65 years. No sex difference in incidence was observed. The implications for policies governing the supply of cytomegalovirus antibody-free blood for transfusion are discussed.
Antithrombin III deficiency.
A moderate reduction of plasma antithrombin activity is an uncommon but clinically important cause of severe thromboembolic disease. In recent years the molecule responsible for the major part of this activity (antithrombin III) has been extensively characterised and the mode of inheritance of familial deficiencies worked out. Over 30 autosomally dominant inheritable variants have been described, the gene for normal human antithrombin III has been sequenced and this information has provided important insights into the reaction of antithrombin with thrombin and the catalytic role of heparin. Further information has been derived by analogy with other serine proteinase inhibitors, in particular alpha 1 antitrypsin. Recombinant DNA methods have been used to produce functionally active AT III which may, in the future, replace human chromatographically-separated AT III as the treatment of choice for clinically important deficiency states. Newer diagnostic techniques, using restriction fragment length polymorphisms and synthetic oligonucleotide probes, hold the promise of more accurate diagnosis and diagnosis in the antenatal period in families possessing some of the fully characterised variants.
Time: a biological dimension.
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Haemolytic uraemic syndrome.
A temporal cluster of three cases of haemolytic uraemic syndrome is described. Prognostic factors are reviewed and the sometimes unpredictable outcome of this rare condition is emphasised.
Dementia in human immunodeficiency virus infection.
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Temporal clustering of transient erythroblastopenia (cytopenia) of childhood.
A temporal cluster of four cases of transient childhood erythroblastopenia is described. In all cases there was an associated transient neutropenia and in one case a transient mild thrombocytopenia. In all cases reticulo-endothelial iron overload was a prominent feature but there was no evidence of a pre-existing chronic haemolytic state. All children made a full recovery with only supportive treatment, although in three cases blood transfusion was necessary.
Paroxysmal nocturnal haemoglobinuria and pregnancy.
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Cyclic eosinophilic myositis and hyperimmunoglobulin-E.
A 40-year-old man had regular cyclic episodes of weight gain and eosinophilic myositis associated with hyperimmunoglobulin-E and hypereosinophilia for 9 years. During the episodes his body weight increased up to 10.8%; eosinophil counts reached 41.3 X 10(-9) cells/L; and IgE levels reached 18 000 IU/mL. These values changed regularly in a definite sequence relative to the clinical state. Attempts to document a parasitic cause were unsuccessful, and several courses of anthelmintic therapy were ineffective. An oral dose of prednisone, 10 mg/d, begun in July 1982 resulted in an immediate lessening of the severity of the episodes and a progressive lengthening of the cycle from 35 to 170 days. No further episodes have occurred since March 1984. The patient is fit and well on prednisone therapy, 12.5 mg on alternate days. This apparently unique syndrome has a benign course and is a cyclic disease involving skeletal muscle as the target organ.
Absorption, excretion, and utilization of an intramuscular iron-poly (sorbitol-gluconic acid) complex, Ferastral.
An iron-poly (sorbitol-gluconic acid) complex (Ferastral) labelled with 59Fe was administered by intramuscular injection to clinically and haematologically normal male volunteers. Urinary excretion of radioactivity was measured for the first 48 hours following injection, and was 2%-10% of the administered dose. Disappearance of radioactivity at the site of injection and accumulation of radioactivity in the liver, spleen, and sacrum were measured by external scintillation counting. Plasma radioactivity was measured at intervals for four days and red cell incorporation of 59Fe reached levels of 29%-57.5%. An unexpected finding was that the highest levels of urinary excretion of radioactivity did not coincide with the highest levels of plasma radioactivity.