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D H Williamson

Publications and source records attributed to D H Williamson.

At least 55 records · Page 3Linked to original sources
PubMed1992

Homologies between the contiguous and fragmented rRNAs of the two Plasmodium falciparum extrachromosomal DNAs are limited to core sequences.

Plasmodium falciparum contains two extrachromosomal DNAs, a 6 kb linear element and a 35 kb circular DNA; both encode rDNA sequences. The 6 kb element rDNAs comprise fragments of both large and small subunit rRNAs. Comparison of these with corresponding rDNA sequences from the 35 kb DNA and E. coli show that sequences conserved between the three are largely confined to highly conserved core regions; in fact, most of the 6 kb rDNA sequences correspond to core regions. Both the 6 kb element and 35 kb rDNAs show less conservation to each other than to E. coli sequences, suggesting that the two extrachromosomal DNAs of P. falciparum are not closely related. The characteristics of the fragmented rRNAs from the 6 kb element suggest they are functional, possibly in mitochondrial ribosomes.

Animals↗
PubMed1992

Chain-length dependency of interactions of medium-chain fatty acids with glucose metabolism in acini isolated from lactating rat mammary glands. A putative feed-back to control milk lipid synthesis from glucose.

The effects of a series of medium-chain fatty acids (C6-C12) on glucose metabolism in isolated acini from lactating rat mammary glands have been studied. Hexanoate (C6) octanoate (C8) and decanoate (C10), but not laurate (C12), decreased [1-14C]glucose conversion into [14C]lipid and the production of 14CO2 (an index of the pentose phosphate pathway). With hexanoate and octanoate, glucose utilization was decreased, whereas decanoate had a slight stimulatory effect on glucose utilization, but there was a large accumulation of lactate. Addition of dichloroacetate (an inhibitor of pyruvate dehydrogenase kinase) decreased this accumulation of lactate and stimulated the conversion of [1-14C]glucose into [14C]lipid and 14CO2. Insulin had no effect on the rate of glucose utilization in the presence of hexanoate. It stimulated the rate in the presence of octanoate and laurate and increased the conversion of [1-14C]glucose into [14C]lipid in the presence of octanoate, decanoate or laurate. The major fate of 1-14C-labelled medium-chain fatty acids (C6, C8 and C12) was conversion into [14C]lipid. The proportion converted into 14CO2 decreased with increasing chain length, whereas the rate of [14C]lipid formation increased. It is concluded that the interactions between medium-chain fatty acids and glucose metabolism represent a feed-back mechanism to control milk lipid synthesis, and this may be important when milk accumulates in the gland.

Animals↗
PubMed1992

Subcellular fractionation of the two organelle DNAs of malaria parasites.

Malaria parasites contain two extrachromosomal DNAs, a 6 kb repetitive linear molecule which is assigned on the basis of its genetic content to the mitochondria, and a 35 kb transcriptionally active circular molecule whose intracellular location is not known. We used the polymerase chain reaction to detect and estimate the numbers of both molecules in sub-cellular fractions derived from the rodent parasite Plasmodium yoelii. The two DNA molecules were not coordinately partitioned by the fractionation process, the 6 kb molecule being more abundant, relative to the 35 kb circle, in a fraction enriched for mitochondria, the converse being true for a less dense fraction of unknown identity. This implies that the two molecules are located in different cellular compartments, and is consistent with other evidence suggesting they have different evolutionary origins.

Animals↗
PubMed1992

Hepatic blood flow and metabolism in severe falciparum malaria: clearance of intravenously administered galactose.

1. Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence. 2. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min-1 kg-1, mean (SD)], but this difference was not statistically significant (P = 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and the liver blood flow estimated from the clearance of Indocyanine Green (rs = 0.71, P = 0.004). 3. The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min-1 kg-1] and convalescent study [12.8 (2.1) ml min-1 kg-1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)]. 4. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study. 5. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Acute administration of tumour necrosis factor-alpha or interleukin-1-alpha does not mimic the hypoketonaemia associated with sepsis and inflammatory stress in the rat.

1. Administration of tumour necrosis factor (cachectin) and of interleukin-1-alpha increased the plasma level of nonesterified fatty acids in fed rats, and in the case of interleukin-1-alpha the blood glycerol level was also increased, suggesting stimulation of adipose tissue lipolysis. There were parallel increases in the plasma level of triacylglycerols. Neither cytokine had significant effects on blood or liver total ketone body (acetoacetate plus 3-hydroxybutyrate) concentrations. 2. In starved rats, the higher plasma non-esterified fatty acid concentration was not increased further by the cytokines. The plasma triacylglycerol level was increased, although the absolute change was less than in fed rats. The ketonaemia associated with starvation tended to be increased by the cytokines, but this was only significant in the case of interleukin-1-alpha. Parallel changes occurred in hepatic ketone bodies. 3. It is concluded that tumour necrosis factor-alpha and interleukin-1-alpha are not responsible for the hypoketonaemia associated with sepsis or other inflammatory states.

Animals↗
PubMed1992

Platelet-activating factor causes hypoketonaemia in starved rats.

1. The aim of this work was to examine whether platelet-activating factor could mimic the hypoketonaemia seen in septic and endotoxic experimental animals. Platelet-activating factor was administered either by the intraperitoneal (high dose) or intravenous (jugular vein, low dose) routes. 2. Intraperitoneal injection of platelet-activating factor (25 micrograms/kg body weight) decreased the blood ketone body concentration (acetoacetate plus 3-hydroxybutyrate) transiently (30 min after injection) in starved rats. Continuous intravenous infusion of platelet-activating factor (40 ng min-1 kg-1 for 5 h) caused comparable hypoketonaemia. 3. The hepatic acetoacetate concentration also decreased transiently after injection of platelet-activating factor and there was an increase in the 3-hydroxybutyrate/acetoacetate ratio. The hepatic ATP concentration decreased at 15 and 30 min after injection of platelet-activating factor. Infusion of platelet-activating factor caused a similar decrease in hepatic ketone body concentration, but no significant change in the 3-hydroxybutyrate/acetoacetate ratio or adenine nucleotide concentrations. 4. Platelet-activating factor administered by infusion, but not by injection, decreased the plasma non-esterified fatty acid concentration. The plasma glycerol concentration also decreased after infusion of platelet-activating factor, suggesting decreased lipolysis in adipose tissue. 5. Changes in plasma insulin concentration or white adipose tissue blood flow did not appear to contribute to the decrease in the plasma non-esterified fatty acid concentration after infusion of platelet-activating factor. However, there was a significant decrease in blood flow to interscapular brown adipose tissue in both the infused and injected groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1991

Effects of platelet-activating factor on lipid metabolism in rats in vivo. Origin of the hypertriglyceridaemia.

Administration of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine; PAF) did not alter the rate of triacylglycerol entry into the plasma. The gastrointestinal absorption of [1-14C]triolein was, however, inhibited by PAF, yet there was increased accumulation of [14C]lipid in the plasma and hypertriglyceridaemia. The half-life of injected [9,10(n)-3H]triolein in the plasma increased by 47%, and there was decreased accumulation of [3H]lipid in brown adipose tissue. This was accompanied by a decrease in lipoprotein lipase activity. The hypertriglyceridaemia induced by PAF appears to be mainly due to decreased peripheral removal, one important site affected being brown adipose tissue.

Animals↗
PubMed1991

Comparison of effects of platelet-activating factor and tumour necrosis factor-alpha on lipid metabolism in adrenalectomized rats in vivo.

The acute metabolic effects of platelet-activating factor (PAF) and tumour necrosis factor-alpha (TNF-alpha) were compared in sham-operated and adrenalectomized rats. PAF caused hyperglycaemia in sham-operated rats, whereas with TNF-alpha there was a slight decrease in blood glucose. Both PAF and TNF-alpha resulted in marked hypoglycaemia in the adrenalectomized rats. Plasma insulin was depressed (about 50%) by PAF and TNF-alpha in sham-operated rats, whereas in the adrenalectomized rats the already low plasma insulin concentration was not significantly altered. Liver glycogen content was the same in control and treated sham-operated rats, but was considerably decreased (about 50%) in the adrenalectomized rats. In sham-operated rats, PAF and TNF-alpha increased plasma non-esterified fatty acids and triacylglycerols, suggesting increased lipolysis, whereas in adrenalectomized rats there was no significant increase in non-esterified fatty acids with PAF, although it still occurred with TNF-alpha. This suggests that the lipolytic effect of TNF-alpha may be direct, whereas that of PAF is indirect, possibly via increased catecholamines in the sham-operated rats. The stimulation (about 3-fold) of hepatic fatty acid synthesis in vivo by PAF and TNF-alpha in sham-operated rats was still evident in the adrenalectomized rats, although the absolute increase was smaller. PAF, but not TNF-alpha increased (100%) sterol synthesis in adrenalectomized rats. It is concluded that PAF and TNF-alpha can increase hepatic lipogenesis in vivo in the absence of adrenal hormones and in the presence of a low plasma insulin.

Adrenalectomy↗
PubMed1991

Masking of diabetic phenotype on a low-energy diet despite persistence of impaired insulin response.

Type 2 diabetes has been postulated to be a "thrifty genotype" that aids fuel conservation; to investigate this hypothesis, type 2 diabetic and nondiabetic subjects, normal weight and obese, were studied after both 6 days on a 700-calorie diet and 6 days on a 2,800-calorie diet. On 2,800 calories per day, the median basal plasma glucose was raised in diabetics compared with nondiabetic subjects (median, 5.5 and 4.5 mmol/L, respectively; P = .003), but on the low-energy diet there was no difference (4.1 and 3.7 mmol/L, respectively; P greater than .05). Basal plasma insulin levels were similar in the diabetic and nondiabetic subjects and were twofold to threefold higher on the high- than low-energy diet in both diabetic (median, 7.8 and 3.1 mU/L on high- and low-energy diets, respectively; P = .007) and nondiabetic subjects (6.8 and 2.6 mU/L, respectively; P = .005). Similarly, the postprandial insulin concentrations increased to the same degree on the high- compared with the low-energy diet in diabetic (median postprandial increment, 14.9 and 3.4 mU/L; P = .005) and nondiabetic patients (9.5 and 3.0 mU/L; P = .005) and the beta cells in type 2 diabetes appeared to modulate normally to different calorie intakes. On both diets, the diabetic subjects had an impaired first-phase insulin response to an intravenous glucose load compared with nondiabetic subjects (high-energy diet median first-phase increment, 4.3 and 21.2 mU/L in diabetic and nondiabetic subjects, P = .0007; low-energy diet, 4.0 and 20.4 mU/L, respectively, P = .003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Organisation and expression of small subunit ribosomal RNA genes encoded by a 35-kilobase circular DNA in Plasmodium falciparum.

A restriction map of the 35-kb circular DNA molecule of Plasmodium falciparum showed that a region of about 6 kb, encoding both a large and a small subunit ribosomal RNA gene, has been duplicated in inverted orientation. The complete sequence of one small subunit rRNA gene is presented as well as an analysis of transcripts from erythrocytic stage parasites. Comparative sequence analysis of the rRNA gene and the proposed secondary structure of the rRNA suggest that it is of organellar origin. Intriguingly, while some characteristics of the small subunit rRNA gene are similar to mitochondrial sequences, others are more like those of plastids. The origin of the circular DNA molecule and evolutionary implications of its genetic content are discussed.

Animals↗
PubMed1991

A circular DNA in malaria parasites encodes an RNA polymerase like that of prokaryotes and chloroplasts.

A 3.5-kb Sau3AI fragment was cloned from a circular DNA molecule isolated from the human malaria parasite Plasmodium falciparum and found to contain two contiguous open reading frames. These encode portions of beta and beta' subunits of an RNA polymerase similar to prokaryotic and chloroplast RNA polymerases, and contain highly conserved structural elements. The Plasmodium genes are arranged in a polycistronic transcription unit, as in both Escherichia coli and chloroplast genomes, and are transcribed in erythrocytic stages. These results suggest that the circular DNA may be an unusual mitochondrial DNA, or derived from an unidentified organelle. Because the beta subunit of prokaryotic RNA polymerases is the specific target of the antibiotic rifampicin, our observations may explain the high sensitivity of P. falciparum to this drug in vitro and indicate a new target for chemotherapy.

Amino Acid Sequence↗
PubMed1991

Have malaria parasites three genomes?

Recent efforts to define the mitochondrial genome of malaria parasites have uncovered an unexpected complexity: there are two almost totally dissimilar organellar DNA molecules. lain Wilson, Malcolm Gardner, Jean Feagin and Donald Williamson discuss the surprising possibility that Plasmodium may have, in addition to the nuclear genome, two unrelated organellar genomes, one evidently mitochondrial and the other of unknown function.

Journal Article↗
PubMed1990

Evidence that use of Triton WR1339 underestimates the triacylglycerol entry rate into the plasma of lactating rats owing to continued accumulation of lipid in the mammary gland.

Measurement of the entry rate of an intragastric load of [14C]triolein into the plasma in the presence of Triton WR1339 gave similar values for virgin and weaned rats, but significantly lower values for lactating rats. This decreased entry rate (65%) in lactating compared with virgin rats was due to a failure of Triton WR1339 to inhibit the accumulation of [14C]lipid in the mammary gland. This is further evidence that mammary-gland lipoprotein lipase behaves differently from that in white adipose tissue or muscle.

Adipose Tissue↗
PubMed1990

Inhibition of sterol but not fatty acid synthesis by valproate in developing rat brain in vivo.

The effect of administration of valproate on lipogenesis in the developing rat brain in vivo was studied. Valproate inhibited by 21-38% the rate of 3H2O incorporation into brain sterols, without significantly affecting fatty acid synthesis. Similarly, R-[2-14C]mevalonate incorporation into sterols was inhibited by 33-54%; the low rate of fatty acid synthesis under these conditions was not affected by valproate. Plasma ketone bodies decreased after treatment with valproate. Valproate inhibited (about 50%) both sterol and fatty acid synthesis in livers of weanling rats. It is concluded that valproate can specifically inhibit sterol synthesis in the brain during development, in part at a stage after mevalonate formation, and also by decreased exogenous precursor supply.

Aging↗
PubMed1990

Metabolic effects of platelet-activating factor in rats in vivo. Stimulation of hepatic glycogenolysis and lipogenesis.

1. The effects of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphocholine; PAF) on hepatic metabolism in vivo in rats were studied. 2. PAF stimulated synthesis of hepatic lipid (saponified and non-saponified) in a dose-dependent fashion and caused hypertriglyceridaemia. There was no effect of PAF on lipogenesis in isolated hepatocytes. 3. High doses of PAF also decreased hepatic glycogen. 4. All doses of PAF decreased plasma insulin, and this was accompanied by hyperglycaemia, except at the lowest dose. 5. The selective PAF-receptor antagonist L659.989 prevented the stimulation of lipogenesis, but indomethacin did not.

Animals↗
PubMed1990

Reciprocal changes in amino acid metabolism in mammary gland and liver of the lactating rat on starvation and refeeding as indicated by the tissue accumulation of alpha-amino[1-14C]isobutyrate.

Measurements of the tissue accumulation in vivo and in vitro by hepatocytes and mammary-gland acini of alpha-amino[1-14C]isobutyrate ([1-14C]AIB) were compared in virgin and lactating rats. The results indicate the existence of a reciprocal relationship between mammary gland and liver for AIB accumulation that is dependent on the lactational and the nutritional state of the rat. This suggests that amino acids are preferentially directed to the mammary gland during active lactation.

Amino Acids↗
PubMed1990

Ty virus-like particles in the Saccharomyces cerevisiae strain NCYC74.

Electron microscopic analysis of thin sections of Saccharomyces cerevisiae NCYC74 has revealed the presence of many clumped cytoplasmic particles that morphologically resemble Ty element virus-like particles (VLPs). Accumulation of Ty VLPs has only previously been observed in S. cerevisiae strains that over-express a cloned Ty element. The particles in NCYC74 co-purify with Ty RNA, Ty-specific antigens and a reverse transcriptase activity. Furthermore, they appear to be recognized by antibodies to Ty VLPs during indirect immunofluorescence experiments. These observations provide compelling evidence that the cytoplasmic particle in NCYC74 are indeed Ty VLPs.

Blotting, Southern↗