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Biomedical subjects

R D Cooke

Publications and source records attributed to R D Cooke.

15 recordsLinked to original sources
PubMed1992

Cassava cyanogens and konzo, an upper motoneuron disease found in Africa.

Konzo is a distinct form of tropical myelopathy characterised by abrupt onset of spastic paraparesis. Epidemics in East Africa have been attributed to dietary cyanide exposure from insufficiently processed cassava but a study done in Zaire disputed such an aetiology. We investigated a konzo-affected population in rural Zaire and measured the cyanogen content of cassava flour, determined urinary thiocyanate as an indicator of cyanide intake, and compared blood cyanide concentrations in cases and controls. The affected population consumed flour made from short-soaked (one day) cassava roots and thus had high dietary cyanide exposure (urinary thiocyanate in 31 children = 757 mumol/l) compared with the unaffected population (urinary thiocyanate in 46 children = 50 mumol/l) that ate cassava that had been soaked for three days before consumption. 3 konzo patients, but only 2 of 23 controls, had blood cyanide concentrations above 4 mumol/l (p less than 0.01), although serum thiocyanate concentrations were similar. Our findings indicate a causal role in konzo of sustained high blood cyanide concentrations maintained by a deficient sulphur intake impairing cyanide to thiocyanate conversion. The underlying causes of konzo are poverty and food shortage, but a minor improvement of food processing may, as in beri-beri, be preventive.

Adolescent↗
PubMed1991

Sleep difficulties, pain and other correlates.

A multiple regression analysis was used with variables relevant to sleeping problems from a large community health survey in South Australia. The variables that were found to be most strongly correlated with sleep problems were, in order of importance, pain, anxiety, age, somatic health and annual household income, all of which accounted for 22% of the variance. Weight problems, depression and sex of the respondent were not so important in this analysis. Arthritis, which often increases with age, appeared to be most strongly associated with pain, explaining in part why sleeping problems increase with age. Anxiety, pain and poor somatic health were most strongly associated with lying awake at night or sleeping badly, and anxiety and pain were most strongly correlated with taking longer to get to sleep. Poor somatic health and anxiety were most strongly associated with waking early, and age and pain were the most important variables in taking tablets to aid sleep.

Age Factors↗
PubMed1989

Community-health needs assessment: use of the Nottingham health profile in an Australian study.

This article reports on the use of the Nottingham health profile (which was developed in the United Kingdom as a valid and reliable indicator of perceived health status) in a community-health survey in Noarlunga, an outer suburban area of Adelaide. The instrument appears valid for use with an Australian population. It was used in Noarlunga to demonstrate a correlation between health status and a range of social and economic variables. The uses of the Nottingham health profile in health-services planning are discussed.

Adolescent↗
PubMed1984

Surgical management of congenital heart disease. A review of 7 years' experience.

This is a review of the results of surgical treatment of congenital heart disease in children aged less than 12 years over the period 1975 - 1981 (1254 cases). The patients are divided into two groups, those treated between 1975 and 1979 (903 cases) and those treated in 1980 and 1981 (351 cases). Only 19,7% of the patients in the first group were under the age of 1 year, but 26,5% in the second group were in this age group. This reflects a change in policy and an attempt at surgical correction at a much younger age than was previously the case. Our present policy in cardiac emergencies in infants will be discussed. Despite the higher percentage of infants aged under 1 year who were treated in 1980 - 1981, the mortality rate was lower than that for the period 1975 - 1979. This probably reflects greater experience in the post-operative management of patients under the age of 1 year.

Age Factors↗
PubMed1979

Prevention of postoperative nausea and vomiting by domperidone: A double-blind randomized study using domperidone, metoclopramide and a placebo.

One hundred and ninety-five female patients of child-bearing age were assessed for postoperative vomiting in a double-blind trial using domperidone, metoclopramide and placebo. Compared with placebo, both drugs were found to reduce vomiting in approximately half the patients who had undergone caesarean section. However, in the group of non-obstetric patients, no statistically significant difference as regards vomiting was shown.

Adult↗
PubMed1976

Purification and characterisation of polygalacturonases from a commercial Aspergillus niger preparation.

The polygalacturonase (poly(1,4-alpha-D-galacturonide) glycanohydrolase, EC 3.2.1.15) activity of Pectinol is resolved into two fractions (E1 and E2) of about equal total activity on DEAE-cellulose. These fractions are purified from other pectinolytic enzyme activity by Sephadex G-75 chromatography. Both E1 and E2 reduce the viscosity of polygalacturonate by 50% after 7% of the glycosidic bonds are hydrolysed. Their activities are not affected by iodoacetate (1 mM) or EDTA (10 mM). E1 and E2 have different molecular weights (35 000 and 85 000, respectively) and different electrophoretic mobilities on sodium dodecyl sulphate polyacrylamide gels. Their pH (4.1 and 3.8 respectively) and ionic strength optima and specific activities also differ. Both enzymes are inhibited at similar rates by diethyl pyrocarbonate at pH 6 but only E2 is protected from this inhibition by 2% (w/v) polygalacturonate. The rate of change of protein absorbance at 250 nm accompanying this inhibition, and the residues are essential for the activities of both E1 and E2. About 2 molecules of carbethoxyhistidine per subunit of E2 and 0.6 molecules per subunit of E1 are present in the completely inhibited enzymes.20

Aspergillus↗
PubMed1974

Calcium and the assays of human plasma clotting factor XIII.

1. A continuous fluorimetric assay for blood-clotting Factor XIII based on the incorporation of dansylcadaverine into casein was investigated. 2. Hammarsten casein was fractionated to yield the beta-casein, which was dephosphorylated and acetylated to give a substrate which itself did not bind calcium and which was not cross-linked by the activated Factor. 3. The modified beta-casein was used as substrate for a continuous fluorimetric assay and as substrate for the incorporation of radioactive glycine ethylester. 4. A linked fluorimetric assay for the zymogen is described. 5. The K(m) for calcium was redetermined and at 0.2mm was in the physiological range and much lower than the values reported by others using substrates which interact with calcium. 6. The K(m) for casein is about 14mum.

Acetylation↗
PubMed1974

The calcium-induced dissociation of human plasma clotting factor XIII.

1. Large quantities of human Factor XIII were prepared from ethanol precipitates of outdated human plasma. 2. Material homogeneous after chromatography on DEAE-cellulose was further resolved into two proteins, A and B, after filtration on Sepharose 6B. 3. Protein A has a molecular weight of 350000 and a subunit structure a(2)b(2) and is activated by thrombin and calcium. Protein B is inactive and probably has a subunit structure b(2). 4. Calcium causes protein A, after thrombin cleavage, to fragment to give protein B and a protein, containing only a' subunits, which is catalytically active. The latter protein slowly forms a misty precipitate which is still active and not cross-linked covalently. This confirms the suggestion of Schwartz et al. (1971) that catalytic activity is only associated with a' subunits. 5. Iodoacetate, which inhibits the enzyme, does not inhibit dissociation and aggregation of protein A. 6. The existence of two proteins and the fragmentation are possible explanations for the wide range of molecular weights given for Factor XIII in the literature.

Animals↗
PubMed1974

Calcium and thiol reactivity of human plasma clotting factor XIII.

1. The reaction of iodoacetate, 2-chloromercuri-4-nitrophenol and 5,5'-dithiobis-(2-nitrobenzoate) with thrombin-cleaved Factor XIII (i.e. Factor XIII(a)) was accompanied by enzyme inhibition. 2. The reaction with iodoacetate and 5,5'-dithiobis-(2-nitrobenzoate) was absolutely dependent on Ca(2+), and the rate of reaction increased with the Ca(2+) concentration up to very high, non-physiological concentrations. 3. 2-Chloromercuri-4-nitrophenol reacted with Factor XIII(a) in the absence of Ca(2+), but at a much slower rate. 4. Stopped-flow methods were used to quantify the reaction with 5,5'-dithiobis-(2-nitro-benzoate) because of the Ca(2+)-dependent dissociation of Factor XIII(a) (a'(2)b(2)) and subsequent aggregation of the a' chains into turbid precipitates. 5. The 3-carboxy-4-nitrothio-phenolate released was consistent with the reaction of 2 thiol groups/molecule of Factor XIII(a). The isolated b chains of Factor XIII did not react with either of the chromophoric reagents. This indicated that the a' chains of Factor XIII(a) were responsible for the thiol reactivity of the enzyme. 6. The Ca(2+) dependence of the enzyme inhibition by these thiol reagents was very dependent on protein concentration. This is discussed in relation to the Ca(2+)-induced dissociation of Factor XIII(a). 7. The acceptor substrate, casein, decreased the Ca(2+) concentration required for enzyme inhibition by both the mercurial and the aromatic disulphide compounds. Dansylcadaverine did not affect Ca(2+) dependence of inhibition.

Cadaverine↗
PubMed1974

Calcium-induced dissociation of human plasma factor XIII and the appearance of catalytic activity.

1. The Ca(2+) dependence of the activity of plasma Factor XIII(a) was studied by using the continuous assay based on the incorporation of dansylcadaverine into dephosphorylated acetylated beta-casein (beta-substrate). The K(m) for Ca(2+) is about 0.170mm. 2. At low concentrations of Ca(2+) there was a lag in attaining the steady-state rate. The size of the lag was decreased and eventually abolished if the enzyme was preincubated with a high concentration of Ca(2+) before assay. The concentration of Ca(2+) required to decrease the lag phase by 50% in 10min depended on the protein concentration: at 0.87mg of protein/ml it required 17mm-Ca(2+) and at 0.44mg/ml it needed 10mm-Ca(2+). 3. The concentrations of Ca(2+) required either to abolish the lag phase in the appearance of enzyme activity or to activate the essential thiol for reaction with 5,5'-dithiobis-(2-nitrobenzoate) in 10min incubation were similar at the same protein concentration. This indicated that Ca(2+) induces a conformation change that is responsible for both phenomena. A model is proposed that links this conformation change to the dissociation of the tetrameric enzyme. 4. This was supported by the observation that the addition of excess of b chains to the Factor XIII(a) (a'(2)b(2)) increased the concentration of Ca(2+) required to expose the reactive thiol, and inhibited the Ca(2+)-dependent aggregation of a' chains. 5. Platelet Factor XIII(a) (a'(2)) was inhibited by 5,5'-dithiobis-(2-nitrobenzoate) in the absence of Ca(2+), and no lag phases were observed in attaining the steady-state rate at low Ca(2+) concentrations, thus confirming the model for the activation of the plasma enzyme. 6. The Ca(2+) dependence of platelet Factor XIII(a) indicated that Ca(2+) has an additional role in the enzyme mechanism of the plasma enzyme, perhaps being involved in substrate binding. 7. The dependence of the stability of plasma Factor XIII(a) on Ca(2+) and protein concentration indicates that the decay in activity is related to the tetramer dissociation. 8. beta-Substrate decreased the Ca(2+) concentration required for (1) abolition of the lag phase and (2) enzyme inhibition by thiol reagents. The effect on the former is greater than on the latter. 9. The role of the b chains of the plasma Factor and the evolutionary significance of the plasma and platelet Factors are considered.

Benzoates↗